Optimizing Blood Transfusion Service Delivery across the West African Sub-Region

Abstract

The sub-continent of West Africa is made up of 16 countries: Benin, Burkina Faso, Cape Verde, Ghana, Guinea, Guinea-Bissau, Ivory Coast, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, The Gambia and Togo. As of 2018, the population of the sub-continent was estimated at about 381 million. The main challenge associated with blood transfusion service delivery across the sub-region concerns adequacy and safety. In this chapter, we highlighted the challenges associated with the delivery of a quality blood transfusion service in countries in the sub-region including: implementation of component therapy rather than whole blood transfusion, effective cold chain management of blood and blood products, alloimmunization prevention, implementation of column agglutination and automation rather than the convention manual tube method in blood transfusion testing, effective management of major haemorrhage, optimization of screening for transfusion transmissible infections, optimizing blood donation, implementation of universal leucodepletion of blood and blood products, effective management of transfusion-dependent patients, pre-operative planning and management of surgical patients, management of Rhesus D negative pregnancy and women with clinically significant alloantibodies, implementation of haemovigilance system, implementation of alternatives to allogenic blood, availability and use of specialized blood products, optimizing safe blood donation, enhancing blood transfusion safety, operating a quality management system-based blood transfusion service and implementation of non-invasive cell-free foetal DNA testing. There is the urgent need for the implementation of evidence-based best practices in blood transfusion service delivery across the sub-region to allow for excellent, safe, adequate and timely blood transfusion service delivery across the sub-region.

1. Introduction

Blood transfusion has life-saving potential and can improve the wellbeing and quality of life of anaemic and bleeding patients [1]. However, the major challenge to blood transfusion service delivery across the West African sub region is access to adequate, safe and timely blood transfusion service [2]. Effective blood transfusion requires that blood sourced from the right voluntary non-remunerated blood donor, is rightly screened, processed, stored and distributed. It is the right blood given to the right patient in the right quantity, in the right condition, at the right time, in the right place, for the right clinical indication and that is effective [3, 4]. There are several challenges associated with blood transfusion service delivery across the West African sub-region. In 2016, WHO global status report on blood safety and availability indicated that an insignificant 5.6 million units of blood (4% of the global supply) were collected in Africa with 38 African countries collecting <10 whole-blood donations per 1,000 populations [5]. The West African sub-region and other developing countries have a significantly increased need for blood and constitute a significant part of the global population, yet it contributes an insignificant number of units to the global allogenic blood pool. The rate of blood donation across the sub-region and other developing countries is significantly lower and often from less safe family replacement and commercial remunerated donor rather than from safer, benevolent and altruistic voluntary non- remunerated blood donors. There are 4.6, 11.7 and 33.1 donations per 1000 population in low- income developing, middle -income and high-income countries respectively [5]. In addition, there is a significant variation in the groups that are most frequently transfused in developing and developed countries. In West Africa and other developing countries, a significant 65% of transfusions are given to children <5 years and to manage pregnancy-related complications including ante and post-partum bleeding compared to 76% of blood transfused to patients >65 years of age in developed countries.

The provision of safe, adequate, and timely blood should ideally be the responsibility of the National blood transfusion service (NBTS) and should be an essential part of every nation’s national health care policy. The WHO recommends that every nation should have a centrally coordinated and regionally based National Blood Transfusion Service governed by national blood policy and legislative framework to allow for the maintenance of standards and consistency in the quality and safety of blood and blood products [6]. The NBTS sole responsibility is to coordinate all activities related to blood collection, testing, processing, storage and distribution blood collected from safe voluntary non-remunerated blood donors who form a reliable, safe, assured and stable base of blood donors [7]. Although the national blood transfusion services are present in member countries across the sub region, they have not been able to solve the challenge of ensuring the safety, adequacy and timely blood transfusion service delivery [8, 9].

Blood supply across the sub region is still predominantly dependent on family/replacement and some commercial remunerated donors. Only few donors across the region donate blood voluntarily. The West African sub-region does not seem to be as altruistic as their counterpart in the developed world regarding voluntary blood donation [10].

WHO recommends that all blood donations should be screened mandatorily for transfusion transmissible diseases including, HIV, hepatitis B, hepatitis C and syphilis and that such screening should meet quality management system requirements. The prevalence of TTIs is considerably higher in the West African sub region compared to the high-income developed nations. In the West African sub region, the challenge has been the availability of screening measures, adequately trained personnel and relevant infrastructure that is required to reduce the risk of introducing potentially infected blood from donor in the window phase of infection in the allogenic blood pool. Use of antibody-based screening with its limitation is prevalent for screening of blood donors for HIV and HCV. Blood donor screening most times is not monitored through external quality assessment (EQA) schemes, there is irregular supply and sometimes stock out of screening kits and other consumables [11, 12].

Suboptimal utilization of the limited allogenic bloodstock is another a major challenge. Whole blood transfusion rather than universally leucodepleted component therapy is prevalent across the sub region [13, 14]. National haemovigilance systems and Hospital Transfusion Committees (HTC) required to monitor, improve, and ensure the rational use and by extension the safety of the blood transfusion process are often non-existent in many setting across the sub region [15]. Adverse events, reactions and near misses are not reported and investigated properly. The root causes are not determined neither are the corrective and preventive action implemented in a timely and action-planned format. Clinical audits are seldom implemented and unnecessary non-clinically indicated and unsafe transfusion practices that expose patients to the risk of serious adverse transfusion reactions and TTIs and that reduces the availability of blood products for patients in whom it is clinically indicated are prevalent. There is absence of indication coding tool required to guide the safe, appropriate, and clinical use of blood across the sub region [16]. The decision to transfuse a patient across the sub region should ideally be based on clinical judgement, laboratory-based evidence and the patient’s risk/benefit ratio including risks associated with transfusion and anaemia [17]. There is need to ensure that all transfusion across the region is clinically effective, prevent mortality in acute situations, ensure the reversal of a physiological transfusion trigger, restores adequate tissue perfusion and ensures maintenance of optimum coagulation [18]. There is an urgent need to solve the challenges associated with timely access to a safe and adequate supply of blood products. The aim of this chapter is to highlight the challenges associated with blood transfusion service delivery in the West African sub region and advocate for the implementation of realistic, pragmatic and evidence-based best practices required to optimize blood transfusion service ensuring that there is universal access to safe blood and blood products.

2. Urgent need for the implementation of component therapy in the West African sub-region

Traditionally, blood can be transfused either as whole blood or as one of its components. Blood components include red cell concentrates (RCCs), fresh frozen plasma (FFP), platelet concentrates (PCs) and cryoprecipitate. However, global safety initiatives and evidence-based best practice advocate that donation be separated into components for safety reasons and to facilitate optimal utilization of scarce allogenic blood stock [19]. Blood component therapy (BCT) is the therapeutic use of blood components rather than the wasteful use of whole blood to manage patients. Patients seldom need all the components of in whole blood. Anaemic patients require red cell concentrate, coagulopathy patients with raised international normalized ration (INR) above 1.5 require fresh frozen plasma, thrombocytopenic patients require platelet concentrate while bleeding patients with significantly low fibrinogen level (< 2 g/L for obstetric haemorrhage and < 1 g/L in non-obstetrics haemorrhage) requires cryoprecipitate. BCT involves whole blood being leucodepleted, divided into individual components, and delivered separately. It often requires that a patient receives the specific blood component required to treat their specific deficiency or condition [20]. Component separation was first developed in 1960 aimed at separating blood products from a unit of whole blood using refrigerated centrifuges and controlled conditions of gravitational force and temperature [19]. A considerable number of literatures has accumulated over the past decade indicating that leukocytes present in allogeneic cellular blood components, intended for transfusion, are associated with adverse effects to the recipient [21]. These include the development of febrile transfusion reactions, graft-versus-host disease, alloimmunization to leukocyte antigens and the immunomodulatory effects that might influence the prognosis of patients with malignancy and HIV. Moreover, it has become evident that leukocytes present in whole blood may be the vector of infectious agents such as cytomegalovirus (CMV), Human T-Lymphotrophic Virus 1/11 (HTLV-I/II), and Epstein Barr (EBV) as well as other viruses. Effective stewardship of blood ensuring that several patients potentially benefit from components derived from one unit of donated whole blood is important for economic, supply/demand reasons and to protect the national inventory at times of national blood shortage [22]. Blood safety in developing countries can be improved by more appropriate use of blood components rather than whole blood transfusion and the provision of alternatives such as oral and intravenous iron, erythropoietin, saline and colloids to manage anaemic and bleeding patients. This will facilitate the optimal use of the limited blood supply. Political will and open-mindedness to innovative ways to improve supply, appropriateness, optimal use and safety of blood from blood donors are essential to promote more evidence-based approaches to blood transfusion practice in sub-Saharan Africa. A recent review on blood transfusion in sub-Saharan Africa highlights the gaps in the area of quality, safety, supply and efficacy of blood and plasma products [23]. BCT is evidence-based best practice and constitutes effective stewardship in the management of our scarce blood resource. BCT allows for targeted therapy and maximum utilization of donated whole blood ensuring that several patients potentially benefit from components derived from the unit. It makes economic, supply/demand sense to implement BCT across the West African sub region- a region where there is high demand, but little supply coupled with the challenge of safety of blood and blood products [24, 25]. BCT can potentially protect regional inventory at times of national blood shortage [20]. Evidence-based clinical decision is crucial in ensuring appropriate transfusion practice. Education, training, and competency testing of all healthcare personnel involved in the blood transfusion process is vital in ensuring effective and appropriate clinical use of blood and components. In countries across the West African sub-region, non-leucodepleted whole blood transfusion thrives rather than component derived from leucodepleted whole blood [26]. Previous report indicates that the utility of cryoprecipitate platelet concentrate and other plasma products is low in many settings in sub-Saharan Africa. This is often due to multiple factors; unavailability due to lack of equipment in NBTS for blood product preparation [27] and lack of education and knowledge among physicians on evidence-based best practices on blood management principles. Other factors include logistical issues and lack of laboratory infrastructure to produce blood components. A previous report that investigated the knowledge and practices of physicians on blood component therapy in two tertiary hospitals in Nigeria indicated that although majority of the physicians have a good knowledge concerning BCT, there is however a knowledge-practice mismatch attributable to the unavailability of the various blood components thus limiting optimal practice of BCT [28]. In each country across the sub region, the blood collection service should have the technical capabilities and financial resources required to facilitate the supply of a range of safe blood products adapted to the specific clinical needs in the country, in particular and for labile therapeutic cellular components. Use of blood products should rely on evidence-based clinical practice, a concept which requires a well- structured and operational clinical interface between blood establishments and care centres. Transfusion committees are an operational tool to monitor and record transfusion epidemiology, patient blood management and blood product use within hospitals. A previous report that investigated the clinical utility of component therapy in sub-Saharan Africa indicated that a total of 40 out of the 43 countries studied reported that they have capacity to produce blood components with red cell concentrates being prepared in 35 of the 40 countries while platelets and fresh frozen plasma were prepared in 27 and 30 countries respectively. In most countries in West Africa an insignificant proportion of blood collection is separated into components; Benin 39.2%, Cameroon 2.8%, Burkina Faso 98.4, Central African Republic100, Congo 20.5, Côte d’Ivoire 86.2, DRC45.0, Sao Tome and Principe 85.2, Senegal 20.5, Mauritius 47.6, Gambia0.0, Ghana 2.6, Nigeria 0.0, Guinea 0.4, Madagascar 38.6, Mali 30.4, Togo 72.2, Mauritania 100, Niger 7.2, Tanzania 1.7 and Sierra Leone 0.0 [29]. In Burkina Faso, the blood transfusion centre produces red cell concentrates (RCC) from whole blood by centrifugation or simple gravity to meet the blood component demand for patients suffering from severe anaemia, such as pregnant women and children with malaria [30]. Separating blood into red cell concentrates, platelet concentrates, plasma and cryoprecipitate is a tool that can be implemented across the West African sub region along with universal leucodepletion and possibly virus inactivation treatments. It is vital that the preparation of blood components be guided by clinical requirements, especially to prevent unnecessary wastage of recovered plasma. One practical way to avoid wasting plasma would require cost-effective and tightly controlled processing of qualified plasma from throughout the West Africa sub region to produce polyvalent and hyperimmune immunoglobulins, VIII (to treat patients with haemophilia A and albumin [31]. Fractionation of plasma can generate a range of purified, virally inactivated, protein therapeutics that can potentially reduce some adverse effects (fevers, chills, transfusion-transmitted infections like CMV, HTLV-1 and 2 as well as prevent volume overload) while providing a better treatment for people suffering from haemophilia or immunodeficiency and other diseases that requires plasma derived proteins for the management. The plasma derived from blood component can be fractionated to produce various Plasma-derived Medicinal Products (PDMPs) of significant economic and therapeutic value [32, 33]. The effective implementation of BCT across the West African region is a huge but surmountable technological challenge hindered in many cases by the lack of a fit for purpose and structured national blood transfusion service, suboptimal number of qualified and skilled health workers, uninterrupted power supply challenges and challenge associated with cold-chain management of blood components. These challenges, although daunting, is surmountable and will require the political will by government of ECOWAS countries working together as a team and taking bold steps to implement BCT (Figures 1–6).

Figure 1.

Donation of plasma by apheresis.

Figure 2.

Cold chain management of blood and blood products.

Figure 3.

Alloantibody screening and panel cells.

Figure 4.

Column agglutination technique.

Figure 5.

Blood products and pharmacologic agent used to manage major haemorrhage.

Figure 6.

Evidence-based best practice in the management of transfusion-dependent patients.

2.1 Getting cold chain management of blood and blood products right across the West African sub-region

Blood transfusion is an indispensable part of modern medicine. The efficient and effective use of appropriately stored blood has lifesaving potential. Effective transfusion requires the implementation of several integrated strategies for blood safety including effective cold chain of blood and blood products. A cold chain is a temperature-controlled supply chain of perishable products such as blood, medicines, vaccines that are sensitive to temperature fluctuations and for which a break in the cold chain can affect its clinical effectiveness and potentially cause harm to the patient. The cold chain for the hospital transfusion laboratory is 24 hours a day, 7 days a week and 365 days a year projects that starts from the receipt of the blood from the blood centre to the time the unit is transfused to the patients or otherwise disposed. Good Distribution Practice (GDP) requires that optimum storage conditions are always observed, including during transportation. The ambient temperatures should be measured continually (24 hours, 7-days a week and 365-days a year) for temperature alarm conditions [34]. The optimum storage temperature for red cell concentrate, plasma and platelet concentrate in blood bank refrigerator, freezers and platelet incubator are 2–6°C, −35°C and 20–24°C respectively. In countries with restricted economies including setting across the West African sub region, the poor practice of using domestic refrigerators and freezers for the storage of blood and blood components is prevalent [35]. Although generally affordable, they are not suitable for blood storage because they are not designed for this purpose. The insulation in domestic fridges and freezers are poor and, in the event of power outage, they will not hold temperatures adequately. Furthermore, domestic refrigerators do not have temperature monitoring devices, such as audio-visual alarms for temperatures outside the set limits for the products being stored. In many settings across the West African sub region especially in remote rural areas, hospitals are often dependent on fuel-driven generators for their electricity supplies which may be inadequate to meet their power needs, particularly the special requirements of blood bank refrigerators and freezers that must function round the clock. Frequent power outages sometimes for long duration are prevalent in hospitals that are on the national power grid with a significant negative implication on the quality, safety and wastage of the scarce blood resource. Also, sensitive blood bank refrigerators are often damaged because of power surges that are common in many settings across the sub region. One of the main reasons of ensuring optimum storage of blood and blood products is to minimize the risk of bacterial growth. If blood is kept at temperature higher than the defined limit bacteria that have infiltrated into blood during collection from the blood donor will quickly grow and proliferate [36, 37]. Also, the suboptimum storage of blood at a temperature less than the defined lower limit predisposes the red cell membrane to damage, release of the free radical haemoglobin contained in the cytoplasm with resultant haemolysis that will increase mortality and morbidity [38]. The transportation of blood between and within blood banks and hospitals is often dependent on the availability of cooler boxes that can maintain temperature over long distances and in relatively high ambient temperatures [39]. Across West Africa the use of domestic type (picnic) cooler boxes or other containers that are not validated and are not reliable in maintaining ambient storage temperature is prevalent. The absence of safe validated blood transport boxes can affect the safe movement of blood and blood products and compromise the quality and potentially cause harm to the patient [40]. Scientific evidence exists that indicates that transfusion of RBC units that exceeding defined temperature is associated with a greater degree of haemolysis and septic transfusion reactions [41, 42]. Evidence-based best practice recommend that all boxes used for the transport of blood and blood products be validated with documentary evidence to show that temperature during storage are ambient [34]. Validation is a documented assessment to prove that the requirement for a specific intended use is reliably fulfilled. It is evidence-based best practice that validation of all blood transport boxes be performed in advance to ensure that transport of components is at the right storage conditions and to ensure that the integrity of the blood product is not compromised. Also, the need for regular mapping of blood fridges cannot be overemphasized. The aim for temperature mapping of blood fridges and freezers is to demonstrate by way of documented evidence that the chosen storage area is suitable for the optimum storage of temperature sensitive blood and blood products [43]. There is also the need for blood transfusion laboratories across the sub region to have back up fridges and freezers where products can be transferred in a timely manner (30 minutes’ rule is not compromised) when the routine fridges and freezers malfunctions or are not keeping optimum temperature. The prevailing temperature across the West African sub region is high. The time it takes for the temperature of blood to rise above +6°C when the power supply to the equipment is cut off or when the fridge is left open (holdover time) is dependent on the quality of the insulation of the cabinet and the prevailing temperature in the environment. In the West African sub region where there is a high tendency to use domestic refrigerators and freezers with poorer insulated cabinet for storage of blood and blood product, the challenge is even worse. Temperatures in the lowlands of West Africa are high throughout the year, with annual means usually above 18°C. In the Sahel, the maximum temperatures can reach above 40°C. The hold-over time in these hot environments will likely be shorter and could be worse when there are power outages. The hold-over time is however less critical for plasma freezers, since plasma are stored frozen at −35°C and will usually take about 24 hours before it begins to thaw. Cold chain management of blood and blood products is expensive, complicated, comprehensive, and associated with several logistical challenges [44]. There is a need for countries in West Africa sub region to develop a cost-effective blood cold chain programme that is technologically appropriate, affordable and accessible at all levels of the health care delivery (primary, secondary and tertiary) system. The equipment must meet international standards, together with WHO minimum performance specifications and be correctly used and maintained by all personnel involved. The West African sub region is blessed with a vast amount of green renewable energy potential that is adequate to ensure a universal access to uninterrupted electricity. Heads of State and Government of the Economic Community of West African States (ECOWAS) will need to invest in solar energy to enable her to maximize the solar energy potential in the management of critical infrastructure including the cold chain management of blood and blood products.

2.2 Alloimmunization prevention and antenatal management of pregnant women in West Africa

Currently, there are about 400 red blood cell antigens in 33 blood group systems. Of these, there are 50 different antigens that have the capacity to cause maternal alloimmunization and haemolytic disease of the foetus and the newborn (HDFN). The most clinically significant blood group system is the ABO blood group system followed by the Rhesus and then Kell blood group system [45]. Of the antigens of the Rhesus blood group system the D antigen is the most immunogenic. Individuals positive for the Rhesus D antigen are referred to as Rhesus D positive while those who are negative are Rhesus D negative. The prevalence of Rh D negative group varies in different ethnic populations, with approximately 15.8% of Caucasians, 8% of Blacks, and 1% of Asians being RhD negative [46, 47, 48, 49, 50]. Alloantibodies are produced because of blood group incompatibility between a mum and her developing foetus or because of the transfusion of a foreign red cell antigen to a patient. These alloantibodies are low molecular weight immunoglobulin G (IgG) that can cross the placenta and causing haemolytic disease of the foetus and the newborn (HDFN) as well as haemolytic transfusion reaction (HTR) if the patient is exposed to a red cell antigen in the donor unit to which the patient has the group specific alloantibody. About 1.5–2% of pregnant show the presence of alloantibodies at booking [51] and a further 0.18% of women who had no alloantibodies at booking become immunized and show the presence of alloantibodies at 28-week gestation [52]. Commonly encountered alloantibodies include the Rhesus (Anti-D, anti-C, anti-c, anti-E, or anti-e), anti-K, anti-Kidd (Jka and b), Duffy (Fya and b) and anti-S. Of all these the most encountered are the Rhesus antibodies with anti-D and c predominating [53]. A previous report among Cameroonian women of reproductive age has indicated an anti-D prevalence of 4% among Rh-negative African women [54]. Evidence-based best practices in the management of pregnant women requires the routine antenatal determination of the ABO and Rh D group of pregnant women and alloantibody screening during antenatal booking. This alloantibody screen facilitates the identification of Rhesus D negative women who have developed alloantibodies. Those that are Rhesus D negative and are previously non-sensitized are enrolled into the routine antenatal anti-D prophylaxis (RAADP) program and are universally administered anti- D prophylaxis at the 28th-week gestation and a postpartum injection of anti-D within 72 hours of delivering an RhD-positive infant. This protects the woman from being sensitized by foetal red cells containing the D antigen during the transplacental bleeding that can potentially occur during pregnancy or delivery [54, 55].

Transplacental or fetomaternal haemorrhage (FMH) that occur during pregnancy or during delivery can predispose the mum to sensitization leading to development of anti-D that can cause haemolytic disease of the foetus and newborn (HDFN) in subsequent D-positive pregnancies [56]. Also evidenced best practices in the West recommend that mass foetal blood group by analysis of cell-free foetal DNA in the maternal plasma should be carried out based on the finding that 38% of Rhesus D negative women are likely to be carrying an RhD-negative foetus and would receive the treatment unnecessarily [57]. There are several advantages associated with this practice, firstly, there would be a substantial reduction in the use of anti-RhD immunoglobulin, an expensive blood product in short supply. Secondly, women with an RhD-negative foetus would be spared unnecessary exposure to this pooled human blood product with its associated pain and perceived risk from viral or prion contamination. Also, these women can be spared FMH that would have been carried out following a potentially sensitizing event that occur during such pregnancy [58]. Evidence-based best practice recommend availability of facilities for the determination of FMH (acid elution method, or the Kleihauer-Betke (KB) or Flow cytometry) to enable the quantification of Rhesus D foetal red cells that potentially enters the maternal circulation of a Rhesus D negative mother following a potentially sensitizing event post 20-week gestation or post-delivery of a Rhesus D positive baby. This is to enable the administration of the adequate dose of anti-D prophylaxis to be issued within 72 hours of the sensitizing event to clear the foetal red cells from the maternal circulation and thus prevent the mother from being sensitized to produce immune anti-D that can cause HDFN in subsequent D positive pregnancy [59]. Previous report indicates that a dose of anti-D of 125iu is required to clear 1 ml of Rhesus D positive foetal cell from maternal circulation. Implementation of preventive screening programs for antenatal care in the West has led to a significant reduction in maternal and infant mortality rates to approximately 1 in 7000 compared to 1 in 23 for women living in parts of Africa where antenatal care is poor or sometimes non-existent [60]. In many settings across the West African sub region these evidence-based best practices are often not available. Other challenges include; the absence of universal access to anti-D immunoglobulin for the Rh-negative women and following potentially sensitizing events [amniocentesis, cordocentesis, antepartum haemorrhage, vaginal bleeding during pregnancy, external cephalic version (ECV), abdominal trauma, intrauterine death and stillbirth, miscarriage, and therapeutic termination of pregnancy (TOP)] [61, 62], unaffordability of anti-D prophylaxis [62, 63], lack of facilities for alloantibody screening and identification during antenatal booking [64, 65], lack of alloimmunization prevention during illegal abortions and poor documentation [66]. Knowledge of anti-D prophylaxis among biomedical scientist, obstetricians, pharmacists, midwives, nurses, and traditional birth attendant across the West African sub region needs to be improved [67]. This will facilitate quality antenatal and postnatal care to be offered to Rh-negative pregnant population as well as pregnant women with alloantibodies and improve perinatal outcomes.

2.3 Paradigm shift from convention tube method to column agglutination technique and automation in blood transfusion service delivery in the West African sub-region

Over the years, the conventional test tube (CTT) was being used for pre-transfusion testing [ABO and Rhesus D blood group, Direct antiglobulin test (DAT) alloantibody screen and identification and compatibility testing]. However, recent scientific development in the field of transfusion has led to the discovery of semi-automated and fully automated equipment using Column agglutination technology (CAT) [68]. This technique often includes the use of column agglutination-based cards, centrifugation, and incubation. Larger laboratories are moving towards automation of all the hitherto manual techniques using CTT. The advantages of these automated techniques include elimination of human associated errors, reduction in the risk of exposure to bio-hazardous samples, allows for better traceability, reliability, improved turnaround time (TAT) and throughput [69, 70, 71]. The principle of the CAT is based on the sieving effect of glass microspheres and gel of agglutinated red cells while allowing non-agglutinated cells to filter to the bottom. In principle, the test is performed in a micro column in which red blood cells containing red cell antigens suspended in low ionic strength saline and serum-containing antibodies are pipetted into the microtubes, incubated, and then centrifuged. RBC agglutinates are trapped in the glass bead matrix during centrifugation and the non-agglutinated cells form a pellet at the bottom of the column. The gel or glass microspheres within each column act as a sieve, trapping agglutinated red cells and allowing non-agglutinated red cells to pass through the pores of the gel or glass microspheres to the bottom of the column. A previous report indicated a sensitivity and specificity of 100% with CAT and concluded that the gel technique is better and should be introduced as a replacement to the CTT [72]. The CAT has several advantages compared to the CTT [73]. The antiglobulin testing used for the detection of clinically significant red cell antibodies can be performed using the CAT card impregnated with AHG without the need to wash with the CTT thus eliminating the potential errors associated with suboptimal washing and potential neutralization of anti-human globulin (AHG). Other advantages of this techniques over the CTT is that it allows for the detection of Ig and complement in diagnosis of HDFN, it can be used for ABO, Rh, Kell phenotype, DAT, ABs screen and XM, it is paediatric friendly as only a small quantity of cells and serum is required, no washing is required as in CTT, it is not subjective and the results are clear and readable and does not require a microscope, it is easy to automate, the risk of miss-up is minimal, it is more sensitive and specific and can detect weaker antibodies, it reduces the turnaround time to make compatible units available, result is standardized and can be automated [74, 75, 76, 77]. The CAT, although more expensive than the CTT, has several advantages. Many Blood transfusion laboratories across the West African sub region still rely on the less sensitive CTT. It is highly recommended that government of West African countries should implement the CAT for routine pretransfusion testing across the region to enhance the quality of blood transfusion service delivery.

2.4 Implementing evidence-based best practices in the management of major haemorrhage across the West African sub-region

Haemorrhage from post-traumatic bleeding, intra and post-operative, gastrointestinal, ante and post-partum remains a leading cause of potentially preventable death particularly in the West African sub region. Major haemorrhage is defined as: loss of more than one blood volume within 24 hours (around 70 mL/kg, >5 litres in a 70 kg adult), loss of 50% of total blood volume in less than 3 hours and bleeding more than 150 mL/minute [78]. Experience has shown that early recognition and intervention is critical for survival. In major haemorrhage situation the immediate priorities include prompt arrest or control of bleeding (use of surgical and interventional radiology), ensure optimum tissue perfusion by transfusing red cells concentrate and maintaining optimum blood volume to prevent hypovolaemic shock. A protocol-driven multidisciplinary team approach involving trained, and competency tested major stakeholders (medical, anaesthetic, surgical, transfusion staff and porters) reinforced by clear and effective communication between clinicians, transfusion laboratory and porters. Availability of safe, adequate, and promptly delivered blood components is a key factor in the effective management of MH. Major obstetric haemorrhage (MOH) is prevalent and is a leading cause of maternal mortality accounting for one-third of maternal deaths in Africa [79]. Sub Saharan Africa ranks first in the incidence of maternal mortality globally [80]. Postpartum haemorrhage (PPH) is a common factor responsible for 30 to 50% of Maternal mortality in sub-Saharan Africa [81]. PPH is defined as blood loss ≥500 mL during vaginal delivery and ≥ 1000 mL during caesarean section [82]. It is advocated that low income developing countries can reduce PPH related mortality by approximately 30% if the antifibrinolytic agent (tranexamic acid) is administered promptly at the commencement of bleeding [83]. This treatment is simple and relatively inexpensive and can have a significant effect of survival of women in the West African region [84]. There are several factors that complicates the effective management of haemorrhages (ante- and post-partum) in pregnant women across west Africa; medical records are often incomplete and does not have information on haemorrhage risk and past haemorrhage-related risk associated with patients, absence of routine coagulation test to identify patient that are coagulopathic and are prone to bleeding, absence of blood and products (red cell concentrate, fresh frozen plasma, cryoprecipitate and platelet concentrate), pharmacologic (vitamin K, Prothrombin complex concentrate, tranexamic acid) and non-pharmacologic (surgical and explorative) measures to management haemorrhage, poor management of bleeding- related anaemia in an environment of pre-existing anaemia, timely access to emergency interventions, availability of trained healthcare staff, financial and infrastructural factors, absence and lack of awareness of massive transfusion and major haemorrhage protocols, poor collaborations and communication between local teams responsible for the management of haemorrhage (haematology, blood banking, obstetrics and porters), suboptimal training of obstetricians, nurses, anaesthetists and other relevant health workers on the evidence-based management of obstetrics haemorrhage especially in rural clinics [85, 86, 87, 88, 89, 90]. The three main causes of major obstetrics haemorrhage (MOH) are placental abruption, complications during or after Caesarean Section (CS) and uterine atony [91]. The availability, appropriate cold chain management and appropriate and consistent use of oxytocin as an effective, affordable, and safe drug of first choice in the prevention and treatment for Post-Partum Haemorrhage (PPH) particularly in the third stage of labour is advocated [92]. The biggest obstacle to oxytocin quality is storage and handling before patient use. The storage condition of oxytocin has been widely reported as inappropriate. Oxytocin is a heat-sensitive medicine and should be kept between 2 and 8°C. Challenges associated with the effective use of oxytocin in developing countries include procurement issues, poor supply chain, logistics, suboptimal cold chain management during transport and storage and lack of stable electricity). There is need to optimize the haemorrhage management training for all stakeholders involved in the management of obstetric haemorrhage across the West African sub-region as a way of significantly reducing the detrimental effects of obstetric haemorrhage in the sub-region. Correction of pre-existing anaemia among pregnant women should be incorporated in the strategy for preventing deaths from PPH across the sub region. An enabling environment (human and infrastructural) needs to be created across the sub-region in urban and rural areas that facilitate regular attendance to antenatal clinics to curb the attendant dangers associated with home deliveries. The need to optimize the number of skilled birth attendants (SBA) and community midwives cannot be overemphasized. Government of West African states must take objective, strategic and effective steps to ensure the prevention, early diagnosis and improved clinical management of MOH in furtherance of achieving the Sustainable Development Goals aimed at reducing maternal mortality. Every minute of every day a woman dies from complications of pregnancy or childbirth with about 99% of deaths occurring in the developing world [93, 94, 95]. The maternal mortality ratio of sub-Saharan Africa is more than a hundred times that of the UK with haemorrhage not only accounting for approximately 30% of cases but also the leading cause of maternal death worldwide [96, 97]. PPH is the leading cause of maternal deaths in individual countries in Africa and collectively on the continent [98, 99]. Major haemorrhage protocols (MHP) were introduced to improve the speed and consistency of delivery of red blood cells (RBCs) and other blood components to severely haemorrhaging patients and have been shown in several observational studies to improve outcomes, including mortality providing a clear framework to facilitate a co-ordinated response by a large multi-disciplinary team during the critical time of bleeding [100]. Blood components (red cell concentrate, fresh frozen plasma, cryoprecipitate and platelet concentrate) can play a role in the management of coagulopathy, disseminated intravascular coagulation and thrombocytopenia. For immediate transfusion, group O red cells should be issued after samples are taken for blood grouping and crossmatching. Females less than 50 years of age should receive RhD negative red cells to avoid sensitization. The use of Kell negative red cells is also desirable in this group. Group O red cells must continue to be issued if patient or sample identification is incomplete or until the ABO group is confirmed on a second sample according to local policy. The higher ratio of Fresh Frozen Plasma (FFP): Red blood cells (RBC) is associated with reduced mortality in a major haemorrhage [101, 102] with FFP providing a source of coagulation factors necessary for thrombin generation in the early phase after injury [103]. Cryoprecipitate or fibrinogen concentrate are a good source of fibrinogen. Fibrinogen is critical for effective haemostasis in MOH. Low fibrinogen level is an independent predictor of mortality as well as bleeding [104, 105, 106]. Coagulation is also impaired by hypothermia, acidosis and reduced ionized calcium (Ca²⁺) concentration [107]. Evidence-based best practice indicates that an early and individualized goal-directed treatment improves the outcome among severely injured and bleeding patients [108]. The aim of treatment in major haemorrhage is to rapidly and effectively restores adequate blood volume, prevent hypovolemic shock, allow for adequate haemostasis, optimize the oxygen carrying capacity and blood biochemistry to allow for an early and aggressive correction of coagulopathy, allow for optimal resuscitation and to reduce potentially preventable deaths [109]. The recombinant activated factor VII (FVII, rFVIIa, FXIII), prothrombin complex concentrates (PCC) and antifibrinolytics (tranexamic acid, epsilon aminocaproic acid and aprotinin) have been used for the management of traumatic bleeding [110] and found to produce a reduction in RBC use but not necessarily improvement in mortality. More recently, viscoelastic assays (rotational thromboelastometry – ROTEM or thromboelastography– TEG) have been advocated [111]. Early recognition of a coagulopathy and subsequent monitoring is vital to both initiate and maximize resuscitation therapy. Massive transfusion guidelines use laboratory tests such as prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen to monitor major haemorrhage and guide blood component replacement [112]. Targeting coagulopathy alongside changes to surgical and anaesthetic practices (damage control surgery/damage control resuscitation) has led to a significant reduction in mortality rates [113]. The transfusion of large volumes of red cells and other intravenous fluids that contain no coagulation factors or platelets causes dilutional coagulopathy and hyperfibrinolysis). Non-blood components and non-pharmacologic measures to manage major haemorrhage include; direct pressure/tourniquet if appropriate, stabilization of fractures, surgical interventions (damage control surgery, interventional radiology, use of endoscopic and obstetrics techniques and thromboelastometry [114, 115]. Government of West African States will need to implement evidence-based best practices; implementation of major haemorrhage protocols, availability of coagulation testing to diagnose coagulopathy and to provide evidence-based indication for blood products to manage coagulopathy. Thromboelastometry, use of tranexamic acid and other relevant pharmacologic agents required to effectively manage coagulopathy and fibrinolysis is advocated along with the implementation of component therapy in a bid to reduce the incidence of preventable major haemorrhage-related death in the sub-region.

2.5 Optimizing screening for transfusion transmissible infections (TTI’s) in the West African sub-region

Safe appropriately screened and clinically indicated blood transfusion saves lives and improves the quality of life and life expectancy of millions of patients globally [116]. However, donor blood that has not been properly screened is an important mode of transmission of TTI’s including HIV, hepatitis B, hepatitis C and syphilis and other transfusion-transmissible infections [117]. Also, these infections can also be transmitted through several different routes; sexual contact, injection practices and cosmetic treatments and rituals (piercing, tattooing, scarification, injections with collagen or botulinum toxoid (botox), electrolysis and semi-permanent make-up). Strict donor selection criteria minimize the risk of transmission of infections from blood donors to recipients [118]. Transfusion safety begins with the recruitment of healthy voluntary non-remunerated blood donors. A fundamental part of preventing TTI is to notify and counsel reactive donors. Donor notification and counselling protect the health of the donor, prevent secondary transmission of infectious diseases to sexual partners, reduces risk of vertical transmission and provide feedback about the effectiveness of donor selection procedures such as pre-donation education and medical history [119]. There is need for government of West African States to implement WHO recommendation to implement holistically across the sub region and as a minimum the screening of all blood donations for TTIs [Viral (HBV, HCV, HIV), Bacteria (syphilis) or Protozoan (malaria)]. The screen of all blood donations should be mandatory using the following markers as a minimum requirement; HIV-1 and HIV-2 (a combination of HIV antigen-antibody or HIV antibodies); Hepatitis B (hepatitis B surface antigen (HBsAg); Hepatitis C (a combination of HCV antigen-antibody or HCV antibodies) and Syphilis (Treponema pallidum pallidum): screening for specific treponemal antibodies [120]. Although screening of blood donors is a way to potentially reduce the risk of transmission of TTI’s to recipient, however screening process alone irrespective of how high-quality the assays and systems, cannot eliminate the risk of the donor being in the window phase of infection, failure due to assay sensitivity or testing errors. Also, there is the possibility that a blood donor may be infected with an infectious agent for which donations are not routinely screened. Other factors to consider include the timing of infection, the length of the window period (time between exposure to an infective agent and the first detection of a defined marker of infection), the incubation period (time between exposure to an infective agent and the onset of associated symptoms). Screening of blood donors must be implemented as an adjunct to effective donor selection process to further enhance blood transfusion safety. Blood donor selection is the first crucial step in the process of ensuring blood safety as it helps to significantly reduce risk through the deferral process prior to donation, of individuals with identified risks that may be associated with infection [121, 122]. A fundamental part of preventing TTIs is to notify and counsel reactive donors. Donor notification and counselling protect the health of the donor and prevent secondary transmission of infectious diseases [123]. Although transmissions of viruses (HIV-1 and HCV) had occurred as late as 2009 due to nucleic acid testing (NAT) failures because of low level of viraemia and/or suboptimal amplification efficiency [124]. Blood transfusion is safer now than it has ever been through the implementation of evidence-based best practices and continuous improvements in donor recruitment, screening, testing of donated blood using increasingly sensitive and specific assays and by implementing appropriate and safe clinical use of blood [125]. Serologic testing for TTI’s had historically been the foundation of blood donor screening, while newer strategies like nucleic acid testing (NAT) have helped to further shorten the challenge of the window period and by extension enhance blood safety [126]. Currently, no technology exists to completely detect all window period donations. No matter how sensitive NAT becomes, we may never be able completely eradicate the risk of exposure-to-seroconversion window period. An ambitious policy for the collection of 100% of blood from safe voluntary non-remunerated donors who donate blood out of altruism should be implemented universally across the sub-region. There is the urgent need for the implementation of the use of the more sensitive NAT testing for transfusion transmissible viral infection across the West African sub region to reduce the risk of potentially introducing donor blood in the window phase of infection and to further improve blood safety. Donors should universally undergo pre-donation counselling to educate them about the risk of infections and the window period. There is an urgent need to formulate a sub-regional policy guideline for notification of all reactive blood donors.

2.6 Changing the narrative about blood donation in the West African sub-region

Urgent concerted efforts are needed in the West African sub region to correct the blood supply deficit and increase the pool of voluntary non-remunerated blood donors. This is expected to significantly improve blood transfusion safety and positively impact the health indices in the sub region [126]. The World Health Assembly in its resolution WHA.63.12 recommended that all countries begin to use only voluntary, non-remunerated blood donors (VNRDs) [127]. The WHO has consistently emphasized blood sourcing from VNRDs, due to their markedly reduced chances of harbouring and transferring TTIs [128]. This recommendation has been reiterated and supported by an increasing body of evidence from researchers in the sub region [129, 130, 131]. Unfortunately, several studies in Nigeria in the last couple of years have shown that VNRDs constituted a small fraction of the blood donor pool, this obviously has serious implications for transfusion safety [132, 133]. A previous report [134] chronicled the social demographic information of blood donors in sub-Saharan Africa and reported that commercial blood donors were all males while the median ages of voluntary and family donors were 18 years and 30 years, respectively. Similar studies in Nigeria had equally identified a male dominated donor pool as well as young adults as the predominant donor age group [135]. Unfortunately, this age distribution has also been associated with the highest carriage rates of TTIs (arising most probably from increased involvement in high-risk sexual behaviours and experimentation). This factor poses a huge challenge to the subcontinent’s efforts towards attaining blood transfusion safety [136]. VNRD are the safest because they are altruistic and have the highest tendency to self-deferral when they are exposed to a risk of contracting TTIs. In SSA, most blood donors are family replacement donors [137]. Mauritius is one good example nation in the sub-Saharan Africa that has done remarkably well with implementation of the guidelines. About 86.2% of the blood donors in that country were VNRDs as of 2016. Mauritius has also embarked on use of nucleic acid testing as opposed to enzyme-linked immunosorbent assay (ELISA) that was previously in use and since 2010 has embarked on aphaeresis method of blood collection and separation. These developments have made transfusion medicine in Mauritius very safe [138]. Government of countries across the West African sub-region will need to learn from the excellent practice in Mauritius by investing significantly in education, mass mobilization and campaign to facilitate a significant increase in the number of voluntary blood donors in a bid to bridging the wide gap between demand and supply of blood and blood product as well as enhance blood transfusion safety across the sub-region.

2.7 Universal leucodepletion of blood and blood products and prevention of development of anti- leukocyte antibodies

The average content of leucocytes in donated human whole blood is 10⁹/unit. Leukoreduction is the reduction to ≤1 × 10⁶ or < 5 × 10⁶/ leucocytes per unit after preparation and with a minimum of 85% of red cells still retained [139, 140]. Clinical evidence indicates that the risk of non-haemolytic febrile transfusion reactions is significantly reduced by leucodepletion. This procedure prevents alloimmunization to HLA antigens in transfusion-dependent patients [141]. Leucocyte antibodies due to alloimmunization by a foreign HLA antigen can cause febrile transfusion reaction in subsequent transfusion involving HLA and granulocyte specific antigens [142]. Leucocyte depletion can be achieved by using filters (cotton, cellulose acetate etc.), apheresis, red cell washing, buffy coat removal after centrifugation and freezing and subsequent glycerol removal of red cells [143]. Leucodepletion of donor blood using leucodepletion filters is considered the threshold for reducing the risk of alloimmunization against leucocyte antigens and potentially eliminating transfusion reaction associated with leucocyte antibodies. The importance of transfusion of leucodepleted blood products cannot be over emphasized. Apart from reducing the incidence on non-haemolytic febrile transfusion reaction, it reduces the risk of alloimmunization to platelet antigens that can predispose patients to develop platelet antibodies and becoming refractory to platelet transfusions (critical for MDS and aplastic anaemia patients who requires long- term platelet). It also significantly reduces the risk of transmission of variant Creutzfeldt Jacobs Disease (vCJD) and Cytomegalovirus (CMV) infection. Leucocytes is vector of CMV, HTLV-I/II, EBV & other viruses that can potentially to infection particularly in neonates, pregnant women, HIV patients and organ transplant patients. Leuko reduction is also associated with reduction in the risk of transfusion associated graft versus host disease (TA-GVHD) in immunocompromised patients [142]. Leucocytes in whole blood are believed to have immunomodulatory effects that can potentially influence the prognosis of patients with malignancy, increase the risk of post-operative infection and HIV progression [20]. Government of West African countries need to implement a policy on universal leucodepletion of all blood and blood products transfused across the sub region. This has the potential to prevent primary alloimmunization to HLA antigens and its attendant negative effects and make transfusion safer.

2.8 Optimum management of transfusion dependent patients across the West African sub-region

Transfusion dependence (TD) is a term that usually describes patients receiving regular red cell concentrate and/or platelet concentrate transfusions more frequently than every 8 weeks due to persistent anaemia and thrombocytopenia. Regular transfusion of red cells and platelets are required in these patients to reduce the symptoms of anaemia and thrombocytopenia by increasing the number functional red cells and platelets in the recipient’s circulation. Various diseases can lead to transfusion-dependency, most notably myelodysplastic syndromes (MDS), aplastic anaemia and thalassemia). Platelet transfusion is clinically indicated in thrombocytopenic patients with chronic bone marrow failure including patients on low dose oral chemotherapy, to manage patients with chronic bleeding of WHO grade 2, above, or as prophylaxis for patients with low platelet count who are going for invasive procedure that is associated with bleeding [144]. The wellbeing and the quality of life of TD patients across the West African sub region can be optimized by the radical implementation of evidence-based best practices; blood intended for TD patients should be sourced from regular voluntary non-remunerated blood donors; unit should be universally leucodepleted, appropriately screened used sensitive assays and technology to reduce the risk of transfusing donor blood in the window phase; extended red cell phenotyping must be implemented for Rhesus (C, c, E, e) and Kell as a minimum; patients should be transfused ABO, Rhesus and Kell antigen compatible unit; effective pre-transfusion testing including alloantibody screening and a full IAT cross-match particularly for patients with history of alloantibodies as well as implementation of the use of chelating agent to reduce the iron overload related challenges in these patients [145]. Single donor apheresis platelets offer several advantages over random pooled platelets, including the potential for crossmatching, reduction in net donor exposures, maintenance of ABO-compatibility, improved inventory management, diminished rate of alloimmunization and better platelet increments in the recipient [145]. The use of apheresis platelets in TD patients can prevent the incidence of platelet refractoriness often associated with poor post-transfusion platelet increments resulting from the presence of platelet alloantibodies. Evidence-based best practice in preventing alloimmunization to platelet antigens is limiting recipients’ exposure to human leukocyte antigen specificities by using single-donor apheresis platelets, filtration to reduce the number of human leukocyte antigen-bearing leukocytes as well as pre-transfusion of gamma irradiation to decrease platelet antigen immunogenicity [146]. Transfusion dependent patients who require platelet transfusion on a regular basis should ideally be transfused apheresis rather than pooled platelets. The advantages are numerous; reduction of donor exposures may decrease the risk of TTIs as well as reduce the risk of developing alloimmunization to foreign platelet antigens in the pooled platelets. The platelet yield from apheresis unit is 6 times higher than from pooled platelets and other transfusion-related complications [2]. Evidence-based best practice from the developed economies recommend the determination of extended phenotyping for TD patients at a minimum for the most clinically significant blood group antigens; Rhesus (C, c, D, E, e) and Kell and where feasible a full red cell phenotype/genotype panel for all clinically significant red cell antigens. For non-transfusion naïve patients, molecular testing rather than serologic testing is indicated. These patients should ideally receive as a minimum requirement ABO, Rhesus (C, c, D, E, e) and Kell compatible red cell product. The aim of this best practice is to reduce the risk of alloimmunization against these clinically relevant red cell antigens [147]. Government of West African States need to urgently develop policies, guidelines as well as promote the implementation of evidence-based best practices that will enhance the management of TD patients and reduce morbidity. Extended phenotype should be carried out prior to commencement of transfusion therapy to ensure that they receive clinically significant antigen negative donor blood that can commonly cause alloimmunization in a particular population. Extended red cell typing is required for the management of TD patients to confirm the identity of suspected alloantibodies or determine the specificity of potential additional antibodies that may be formed in the future [148]. Effective pretransfusion testing including alloantibody screening, panel testing for those whose alloantibody screen is positive and crossmatch of antigen negative units using appropriate technologies (IAT and column agglutination technique) should be implemented universally across the sub region. TD patients who require platelet transfusion on a regular basis should ideally be transfused apheresis instead of pooled platelets.

2.9 Best practices in pre-operative planning and management of the transfusion needs of patients

There are certain priorities in meeting the blood transfusion needs in surgical patients; the need for pre-operative optimization of the haemoglobin level (management of anaemia), pre-operative management of coagulopathy and bleeding predisposition to minimize blood loss intraoperatively and post operatively and avoidance of unnecessary transfusion post operatively [149]. In patients scheduled for elective surgeries, it is critical that blood management is planned even before a patient is referred for surgery at the primary care levels working collaboratively with the preoperative assessment clinic at the hospital. A full blood count should be done at least 6 weeks prior to surgery. If anaemia is identified, effort should be made to identify the cause of anaemia (iron deficiency, chronic kidney disease) and remedial action taken to treat the anaemia and potentially optimize the haemoglobin level using pharmacologic alternatives like oral, IV iron, erythropoietin and in some cased red cell transfusion. Patients who are anaemic pre-operatively are more likely to be transfused with allogenic blood [150]. Evidence has shown that pre-operative anaemia is an independent risk factor for increased morbidity and mortality in surgical patients [151]. In patients with severe anaemia and acute coronary syndromes red cell transfusion is a significant predictor of mortality (there is need to optimize tissue (perfusion to vital organs) when the use of pharmacologic agent will not produce a timely optimization of haemoglobin of the patients). Also, the preoperative assessment clinic should also be able to identify patients who are going for significant bleed prone surgery and those with increased risk of bleeding (patients with liver disease, those on anticoagulants therapy like warfarin, low molecular weight heparins (LMWHs) and direct oral anticoagulants like dabigatran, apixaban and rivaroxaban as well as those on antiplatelet therapy like clopidogrel or aspirin for whom remedial actions such as use of prothrombin complex concentrate (PCC), antifibrinolytic agents, fibrinogen concentrate, fresh frozen plasma, cryoprecipitate, platelet concentrate and temporary withdrawal of haemorrhage prone medication where possible and safe [152, 153]. Patients going for bleeding prone elective surgeries can be identified who potentially can be candidates for Pre-deposit autologous donation (PAD). This is vital particularly in patients who do not accept allogenic blood transfusion based on their religious beliefs, patients that have a rare blood group and those that have alloantibodies against a high incidence antigen for which it may be difficult to source blood for transfusion [154]. It is evidence-based practice to evaluate patient predisposition (coagulopathic status) to bleeding prior to surgery. This is vital to possibly take remedial actions prior to surgery in a bid to minimize significant blood loss during surgery. Basic laboratory testing includes determination of international normalized ratio (INR), activated partial thromboplastin time (APTT) and fibrinogen levels (FIBC). Patients with INR and APTT ratio > 1.5 as well as fibrinogen level < 1 g/L are at a high risk of bleeding during surgery [155]. The results of these laboratory test will provide justification to take remedial steps to correct identified coagulopathic status and clinically indicated pharmacologic (antifibrinolytic agents like tranexamic acid, vitamin K, prothrombin complex concentrate, fibrinogen concentrate) or management with blood products (FFP, cryoprecipitate and platelet concentrate). It is also vital to identify patients that can potentially benefit from blood-sparing techniques like acute nomovolaemic haemodilution (ANH) and perioperative cell salvage (PCS) [156, 157]. It is evidence-based best practice to ensure that patient scheduled for surgery has pre transfusion test for the ABO, Rh D group and alloantibodies screen and that patient meet the 2-sample rule (patients’ blood group and alloantibody screen must have been tested on 2 samples taken from two separate venipuncture by two different clinical staff at least a minimum of 15 minutes apart to ensure we have a confirmed group on the patient). By the implementation of this best practice, we can identify patients with rare blood groups and those with alloantibodies for which efforts has to be made in advance to identify the alloantibodies present as well as source antigen negative donor units and possibly crossmatch the units prior to surgery. This is to ensure timely provision of blood if patients begin to bleed intraoperatively or post operatively [158]. It is best practice that we are avoiding unnecessary transfusion post operatively by being conservative and not liberal by the evidence-based use restrictive transfusion triggers ensuring individualized management to prevent unnecessary transfusion particularly in patients that are haemodynamically stable while ensuring safety and effectiveness [159, 160]. This can mean utilizing blood test and presence of symptoms to minimize blood loss and prevent unnecessary transfusion, use of endoscopic radiology and sealants to minimize blood loss, use of post-operative cell salvage and reinfusion if clinically indicated and use of pharmacologic agents (oral or IV iron, and erythropoietin) to optimize the haemoglobin level of patients post operatively and by so doing achieve a reduction in exposure to allogenic blood [161, 162, 163, 164, 165]. Patient blood management (PBM) in surgical patients is important for a number of reasons; to optimize the patient’s erythropoiesis and haemoglobin level, minimizing blood loss in the patients intra and post-operative and optimizing and exploiting the patients physiological reserve to ability to tolerate anaemia [166]. Many of these best practices are not being implemented in many settings across the West African sub region. This is often the cause of suboptimal management of surgical patients in the subregion that is responsible for preventable deaths from haemorrhage. Government of West African nations will need to implement evidenced best practices to ensure the optimum management of surgical patient, reduce the need for unnecessary transfusion and facilitate the optimum utilization of our limited allogenic bloodstock.

3. Evidence-based management of rhesus negative pregnancy and patients clinically significant alloantibodies

Human red blood cells carry many antigens on their surfaces. The most important of these antigens belong to the ABO system and the Rhesus (Rh) blood group system. The D antigen is the most important antigen of the Rhesus system. People with the Rhesus D (RhD) antigen are referred to as RhD positive, and those without it as RhD negative. A baby inherits its blood type from both parents. Therefore, a mother who is RhD negative can carry a baby who is RhD positive. During pregnancy, because of trans placental bleeding, a small amount of foetal blood can enter the maternal circulation [an event called feto-maternal haemorrhage (FMH)]. The presence of foetal RhD-positive cells in mum’s circulation can sensitize the mum triggering an immune response leading to the production of alloantibodies against the RhD antigen (anti-D antibodies). This process is called sensitization or alloimmunization. There are over 600 red cell antigens, which are separated into 30 blood group systems. The presence or absence of these antigens in an individual is important, because they determine the type of blood that should be given if they require a red cell transfusion. If a woman is exposed to red cells containing a foreign red cell antigen which they themselves lacks, it can trigger an immune response leading to the formation against the foreign red cell antigen. Such an antibody can cause extravascular and/or intravascular haemolysis when the recipient is subsequently exposed to the same antigens. Antibodies can either be allo (antibody to an antigen that an individual lacks) or autoantibodies (antibody to an antigen a person has). Alloantibodies are formed in response to pregnancy (blood group incompatibility between the mum and her developing foetus), transfusion (donor red cell containing antigens that are foreign to the recipient), or transplantation (graft containing antigens that are foreign to the recipient). Alloimmunization resulting in the development of one or more clinically significant red cell, leucocyte and platelet antibodies is a vital complication in chronically transfused patients [167, 168, 169, 170]. Multiple red cell transfusion could predispose to the formation of clinically significant titres of lytic antibodies, which may cause haemolytic disease of the foetus and newborn (HDFN) or haemolytic transfusion reaction (HTR). Patients with haemoglobinopathies and other TD patients that require regular blood transfusions are particularly at a higher risk of sensitization and development of red cell alloantibodies [2, 171]. The magnitude of red cell sensitization in Nigeria was highlighted in the independent reports by Ugwu and Colleagues (Benin City, Midwestern Nigeria) [172], Kangiwa and Colleagues (Enugu, Southeast Nigeria) [173], and Jeremiah and Colleagues (Port Harcourt, South-South Nigeria) [174] in which prevalence rates of 9.3, 18.7, and 3.4%, respectively were observed in multiply- transfused patient populations. The presence of these alloantibodies may cause a delay in selecting compatible blood products. Countries in the West African sub region tend to have multiple- ethnic groups, race and genetic heterogeneity. Such multi-ethnic populations are prone to having racial variation in the red cell antigen spectrum that are prevalent with attendant wide variation in commonly identified alloantibodies [65, 175]. Other common factors that facilitate alloantibody formation in persons include: the immune competence, the dose of the antigen the person is exposed to, the route of exposure and how immunogenic the foreign antigen is [176, 177]. Evidence-based best practice in the developed economies requires that alloantibody testing is carried out routinely on all pregnant women presenting to antenatal clinic at booking as well as all patients in whom a red cell transfusion is clinically indicated. The intent of this test is to detect the presence of unexpected red cell antibody in the patient’s serum [178, 179]. Once these antibodies are detected during the alloantibody screening, every effort must be made to identify the specificity of the alloantibody by doing a panel test. The purpose of the panel test is to; facilitate the identification of the alloantibody, determine whether the antibody can potentially cause HTR (to allow for the selection of antigen negative red cells for crossmatch) of HDFN (to allow the monitoring of the titre or quantification of the antibody every 4 weeks from booking until 28 weeks’ gestation and every 2 weeks thereafter until delivery) [180]. The monitoring of the titre or quantification of the antibody helps to determine to what extent the developing foetus is affected by HDFN, to monitor the baby for anaemia along with Doppler ultrasound determination of the peak systolic velocity of blood through the median cerebral artery, determine whether the baby will require intrauterine transfusion (IUT) and to enable the obstetricians make an informed decision to possibly deliver the baby earlier. These evidence-based best practices are not yet completely implemented in many settings in the West African sub region. Testing of pregnant women and donors for other clinically relevant red cell antigens other than ABO and Rhesus D is not routinely carried out. Also, donor units particularly those intended for transfusion to pregnant women and neonates are also not routinely screened for other blood borne transmissible diseases such as CMV, Hepatitis E virus and others like it is routinely done in more advanced countries of the world.

The clinically significant antibodies are those antibodies that are active at 37°C and/or detected by the indirect antiglobulin (IAT) test. Nine blood group systems (ABO, Rhesus, Kell, Kidd, Duffy, MNS, P, Lewis, and Lutheran) are clinically significant as these are known to cause HTR and HDFN. These antibodies are caused predominantly by maternal alloimmunization to blood group antigens expressed by foetal red blood cells. In severe cases, it may result in foetal anaemia with increased risks of foetal death, severe neonatal hyperbilirubinaemia, and kernicterus, jaundice, intellectual retardation, premature birth, abortion, and stillbirth. Most severe cases of HDFN were attributed to Rh(D) incompatibility between a Rh(D)-negative woman and her Rh(D)-positive foetus, with Rh(D) alloimmunization having occurred during a previous pregnancy [65]. HDFN is an important cause of neonatal morbidity and death [181]. Sensitization can happen at any time during pregnancy but is most common in the third trimester and during childbirth. Sensitizations are commonly associated with events during pregnancy that are associated with FMH, such as medical interventions (chorionic villus sampling, amniocentesis, or external cephalic version), terminations, late miscarriages, antepartum haemorrhage, and abdominal trauma [181]. The risk of sensitization is affected by the ABO blood type of the foetus, with a lower risk if it is compatible with the mother’s ABO type. Sensitization depends on the volume of foetal blood entering the mother’s circulation, the magnitude of mother’s immune response and the immune competence of the mum’s immune system. The risk of sensitization is greatest in the first pregnancy and decreases with each subsequent pregnancy. Once sensitization has occurred, it is irreversible. The process of sensitization has no adverse health effects for the mother and usually does not affect the pregnancy during which it occurs. However, if the mother is exposed to the same foreign antigen during a subsequent pregnancy, the immune response is quicker, greater and results in the antibody level being boosted. The anti-D antibodies produced by a Rhesus D negative mother in response to the D positive foetal cells are often low molecular weight IgG antibodies that can cross the placenta and bind to RhD antigen on the surface of foetal red blood cells. These antibody-coated foetal red blood cells are removed from the foetal circulation by the reticuloendothelial system, predominantly the spleen and liver. This is the cause of hepatosplenomegaly commonly seen in babies with HDFN. Foetal anaemia results if the red blood cells are removed faster than they are produced. Severe anaemia can lead to foetal heart failure, fluid retention and swelling (hydrops), and intrauterine death. Before birth, anaemia and hydrops can be managed with intrauterine transfusions, but this carries a 2% risk of foetal loss [182].

Women presenting for antenatal booking are screened for the ABO, Rh D group and for the presence of alloantibodies. The Rh D group categorizes pregnant women into Rh D positive if their red cell contains the Rhesus D antigen and Rh D negative if their red cell lacks the D antigens. The alloantibody screen also determines whether the antibody screen is positive or negative. Those with a positive alloantibody screen are tested for panels to identify the specificity of the alloantibody present. It is evidence-based best practice to recruit all Rhesus D negative non-previously sensitized women into the Routine Antenatal Anti-D Prophylaxis (RAADP) programme and universally offer them universally anti-D prophylaxis at 28-week gestation. The half-life of the anti-D is about 12 weeks, and the aim of the administration is to facilitate the mopping up of all the foetal D positive red cells that enter the maternal circulation as a result of fetomaternal haemorrhage and thus prevent the foreign D positive foetal red cells from sensitizing the mother. By this implementation the risk of anti-D related HDFN in subsequent pregnancy is avoided. This prophylaxis has been used to prevent postpartum disease in Rh D-negative women and has greatly reduced HDFN- related morbidity as well as foetal and neonatal mortality. In the 1960s, studies in the United States and in Great Britain determined that passive immunization of Rh(D)-negative mothers with IgG anti-Rh(D), soon after parturition, could protect women from sensitization against Rh(D) + positive red blood cells of her foetus [183, 184]. This then led to the licensing of IgG anti-Rh(D) for routine post-partum prophylaxis in 1968, however, in 1977 it was demonstrated that, despite adequate post-natal prophylaxis, about 10% of Rh(D)-negative women continued to develop anti-Rh(D) antibodies, presumably due to small, transplacental, foetal-maternal bleed during pregnancy. To manage this challenge, the issue of antenatal administration of IgG anti-Rh (D) preparations was instituted in combination with standard post-partum prophylaxis [185]. Current guidelines recommend that immunoprophylaxis with IgG anti-Rh(D) be given to every non-sensitized Rh(D)-negative woman, as follows; at 28-week gestation during each pregnancy; immediately after delivery of every Rh(D)-positive neonate and following any potentially sensitizing event in pregnancy that could expose the mother to the Rh(D) antigen of the foetus (abortion, miscarriage, abdominal trauma) [186]. The only settings in which antenatal anti-D IgG administration is not necessary is when conception is certain, and the father is also Rh(D)-negative or if the foetus is successfully typed for Rh(D) status by antenatal cell-free DNA testing using maternal plasma [65]. Feto-maternal haemorrhage (FMH) may occur during pregnancy or at delivery. The Kleihauer-Betke (KB) test is a blood test used to measure the amount of foetal red cells that is transferred from a foetus into the maternal circulation [178]. FMH occurs in up to 28% of pregnancies after trauma and the amount of Rh-positive foetal blood required to sensitize the Rh-negative mother is variable, but most patients are sensitized by as little as 0.01 ml of blood [187]. The test utilizes a stain that identifies foetal red blood cells with haemoglobin F in maternal blood. The ratio of foetal: maternal red blood cells can be assessed [188]. The use of flow cytometry for the quantification of haemoglobin F is also available. The aim of the test is to determine the volume of foetal red cells that entered the maternal circuiting following a FMH to facilitate the administration of optimum dose of RhIG required to remove them from the maternal circulation and thus prevent the mother from being sensitized to produce alloantibodies. The Kleihauer-Betke tests have numerous limitations, including low sensitivity, poor reproducibility, and a tendency to overestimate the volume of haemorrhage [188]. An important limitation of the Kleihauer-Betke test is the inability to differentiate between maternal and foetal F cells. This is particularly a challenge in the second trimester of pregnancy when maternal F cells may occasionally reach 5 to 10% as well as in women that hereditary persistence of foetal haemoglobin (HPFH) in whom the count will be falsely raised. Haemoglobin F quantitation by flow cytometry has been reported to be simple, reliable, and more precise than the Kleihauer-Betke test [189]. It is recommended that prophylaxis be within 72 hours of the potential sensitizing event occurring [190]. To prevent sensitization, all D-negative non sensitized women who deliver a D-positive foetus should receive at least a single 300-μg dose of Anti-D within 72 hours of delivery. In addition to the prophylaxis giving during pregnancy, it is recommended that a maternal sample should be obtained post-delivery of a Rhesus D positive baby (approximately1 hour after delivery) and tested for evidence of a FMH [191]. Approximately 17% of Rh D–negative women who deliver Rh D–positive foetus become alloimmunized if Anti- D prophylaxis is not administered appropriately and adequately. Anti- D prophylaxis has been reported to reduce the overall risk of Rh immunization from 13.2 to 0.2%, and testing for large FMH has also further decreased the risk to 0.14% [192]. It is part of modern antenatal care currently in developed countries to offer universally all Rh D-negative pregnant women anti-RhD immunoglobulin IgG injection at about 28- week gestation with a booster at 34-week gestation [193]. However, in countries across the West Africa sub region this evidence-based best practice is not universally implemented due majorly to unaffordability of anti-RhD immunoglobulin [65]. In many of these settings, facility for the effective management of foetuses and babies affected by HDFN such as Doppler ultrasound for diagnosis of foetal anaemia in utero, exchange blood transfusion and ultrasonography guided intrauterine transfusion (IUT) are often unavailable resulting in the preventable deaths of many of the sub region’s future generations [194]. Blood meant for exchange and intrauterine transfusion must meet certain requirements (< 5 days old, free from clinically significant irregular blood group antibodies including high-titre anti-A and anti-B, negative for antibodies to CMV, must be gamma irradiated and transfused within 24 hours of irradiation, the donor should be Haemoglobin S screen negative, and the unit must be leucocyte depleted). Many of which are often not available in many settings across the sub region [65]. These implementations will facilitate the effective management of severely anaemic foetuses earlier in gestation and increase the chances of survival of more severely affected foetuses with the potential for poor neurodevelopmental outcome such as cerebral palsy, deafness, and motor and speech delay [187]. This anti-D immunoglobulin which is administered routinely in the third trimester attaches to the Rhesus D positive foetal cells and are promptly removed from the maternal circulation by the reticuloendothelial system (RES) before they can sensitize the mum to produce alloantibodies. This is known as RAADP. RAADP can be given as two doses of anti-D immunoglobulin of 500 IU (one at 28-week and one at 34-week gestation), as two doses of anti-D immunoglobulin of 1000–1650 IU (one at 28-week and one at 34-week gestation), or as a single dose of 1500 IU either at 28 weeks or between 28- and 30-week gestation [195]. There are several technologies, formulations, and doses of anti- D in use in the United Kingdom [196, 197, 198, 199]. Anti-D immunoglobulin are produced by deliberating immunizing Rhesus D negative men or women donors without childbearing potential who are carefully screened for transfusion transmissible infections [200]. There is need for the universal access to anti D prophylaxis to be provided for all non-sensitized Rh D negative women across the subregion under the RAADP programme and to cover every potentially sensitizing event that takes place during pregnancy and following the delivery of a Rhesus D positive baby. Facilities for determining fetomaternal haemorrhage should be readily available. Cell free foetal DNA testing should be implemented to determine Rhesus D negative women who are carrying Rhesus D negative babies who could be spared prophylactic anti-D. Facility for non-invasive Doppler ultrasound determination of the peak systolic velocity (PSV) through the median cerebral artery (MCA) of foetuses should be available for the diagnosis of foetal anaemia. Blood that meets the minimum requirement for use for intrauterine (IUT) and exchange transfusion should be readily available. There is also the need to optimize the knowledge of Biomedical Scientists, Obstetricians and Neonatologist in the subregion on the effective management of Rhesus D negative pregnancies as well as the prevention and management of HDFN.

3.1 Haemovigilance implementation in the West African sub-region

Haemovigilance is used to describe a set of surveillance procedures that scrutinizes the entire blood transfusion process from the point of collection of blood and blood components from a blood donor to the point of transfusion in the recipient ensuring that all unexpected or undesirable adverse reactions, events reactions, accidents, errors and near misses are reported, investigated in a timely manner and preventive and corrective actions are implemented to prevent their future occurrence. Haemovigilance system facilitates the delivery of a continually improving blood transfusion service [201, 202]. Haemovigilance encompasses the entire blood transfusion process; blood donation, processing, transfusion, post transfusion monitoring as well as reporting and investigation of all adverse events, reactions and near misses related to the blood donation and transfusion. Haemovigilance is indispensable with relation to safety and quality of blood transfusions, and it cuts across any action in the blood transfusion process that directly harm the blood donor [203] or potentially compromises the quality of the blood taken from the donor that put the recipient potentially at risk [204]. An adverse reaction or event is used to describe any unintended response in a blood donor, or a recipient observed during the collection or transfusion of blood and blood components that is fatal, life-threatening, disabling, incapacitating or results in hospitalization or morbidity [205]. Apart from Japan, many Asian countries do not have a fit for purpose haemovigilance system. Many including India are in the process of establishing a haemovigilance system [206]. Haemovigilance is aimed at improving the quality and safety of blood transfusion. In most developed economies haemovigilance is governed by responsible legal authorities [207, 208]. Many countries including the United Kingdom (Serious Hazards of Transfusion [SHOT]), Canada (Transfusion Transmitted Injuries Surveillance System [TTISS]), Netherlands (Transfusion Reactions in Patients [TRIP]), Japan, Russia, Switzerland and the United States of America have dedicated organizations responsible for haemovigilance with the primary responsibility of improving blood safety. International Haemovigilance Network (IHN) is responsible for developing and maintaining haemovigilance and safety of blood and blood components globally [209]. Blood transfusion services in the West African sub region are not as organized and regulated as it is in the West. This has a negative implication on the adequacy and safety of blood and blood products. There are several challenges militating against an effective haemovigilance system across the sub region; lack of standardized tools for data capturing, poor integrity of data captured, poor governance issues, lack of functional hospital transfusion committee (HTC) in general, specialist and teaching hospitals, suboptimal coordination of the NBTS and lack of relevant policies for transfusion practices, lack of indication coding tool to guide the evidence-based clinical use of blood and blood products, lack of policy in place for clinical use of blood, high incidence and increased risk of TTIs, traceability challenges, training-related challenges, poor culture of documentation, incident reporting and investigation of adverse events, poor implementation of recall and quarantining of suboptimal blood and blood products, reaction and near misses associated with the blood transfusion process [210]. There is need for government across the West African sub region to develop a well-organized haemovigilance system in a bid to enhance transfusion safety. Member States of ECOWAS must take all necessary measures to ensure 100% traceability of all blood and blood components collected, tested, processed, stored, released and transfused across the sub region from vein to vein from the blood donor to the recipient. Effective haemovigilance implementation across the West African sub region will require collaboration, effective communication and cooperation between the National Blood Transfusion Centre and the Health establishment on one hand as well as among all the healthcare professionals involved in blood transfusion service delivery [211]. Haemovigilance practice was observed to be lacking in previous studies on transfusion practice in Africa [212]. There is need to put in place a haemovigilance system across the sub region that facilitate the prompt, accurate, efficient, and provable withdraw from distribution chain of blood or blood components that is suboptimal and has a potential to cause harm to the recipient. This is an urgent need to train health workers across the West African sub region on best practices in various aspects of transfusion medicine; blood donation, screening, transportation, storage and transfusion as well as monitoring and documentation of adverse event and reactions with the hope of reporting, investigating transfusion related incident and implementing corrective action and by so doing learning from mistakes and building a culture of continuous quality improvement in blood transfusion service delivery across sub region.

3.2 Suboptimal use of alternatives to allogenic blood across the West African subregion

Not all anaemic and bleeding patients require allogenic blood. Some can benefit from pharmacologic and non- pharmacologic alternatives. The implementation of these alternatives can potentially reduce the dependence and facilitate the optimum utilization of our scare allogenic blood stock. The need for allogenic blood has continued to increase significantly, particularly in developing countries. There are several factors that affect matching demand with supply in sub-Saharan Africa. Escalating elective surgery, increased fatalities from road traffic accidents, poor management of traumatic injuries, intraoperative, post-operative and obstetric haemorrhage, communal crisis, insurgency, banditry, high incidence of malaria related anaemia, sub-optimal management of bleeding predisposition in surgical patients, pregnancy-related complications, suboptimal national blood transfusion services, appropriate infrastructure, trained personnel, and financial resources to support the running of a voluntary non-remunerated donor transfusion service, high incidence of transfusion-transmitted infection, predominance of family replacement and commercially remunerated blood donors, rather than VNRDs [2]. Evidence has shown that not all anaemic or bleeding patients require blood and blood products. Many can benefit from alternatives. Concerns about adverse events associated with allogenic blood transfusion should prompt a review of transfusion practices and justify the need to search for transfusion alternatives to decrease or avoid the use of allogenic blood. There are pharmacologic alternatives that help to stimulate erythropoiesis (iron, folic acid, erythropoietin) and non-pharmacologic alternatives. Strategies to reduce allogenic blood use include the correction of anaemia using pharmacological agents (oral, IV iron and erythropoietin) and management of coagulopathy and bleeding (use of antifibrinolytics, vitamin K and fibrinogen concentrate). Non-pharmacologic measures including preoperative autologous blood transfusion, perioperative red blood cell salvage and normothermia can help to reduce blood loss in surgical patients. Similarly, the use of surgical and endoscopic technology can minimize blood loss and by extension limit the need for allogenic blood. All these strategies can help countries across the West African sub-region in optimizing the use of our limited allogenic blood stocks [213]. There are several challenges associated with allogenic blood transfusion [risk of TTIs (viral, bacterial, parasitic and prion), non-infectious risks including febrile, allergic/ anaphylactic and haemolytic transfusion reactions, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) that warrants the need for the identification and use of transfusion alternatives [214].

3.3 Use of oral and intravenous iron

Iron is an essential micronutrient required for erythropoiesis. Iron deficiency is the most common nutritional deficiency particularly in developing countries. Iron deficiency is the leading cause of anaemia in both men and women [215]. It is a major concern in low-income settings, particularly among children and women of childbearing age. Factors that are responsible for iron depletion are prevalent across the West African sub region [haemorrhage (trauma, surgery, gastrointestinal, ante and postpartum) poor nutrition, age, pregnancy, low socioeconomic status, critical illness, etc.). Treatment of iron deficiency anaemia with oral iron supplements is simple, readily available and affordable. The major limiting factor for oral iron use is the gastrointestinal side-effects and long treatment times needed to resolve anaemia and replenish body iron stores. Non-adherence to therapy is common due to gastrointestinal side effects that limit its efficacy. Intravenous (IV) iron formulations provide a faster replacement, is a safer and effective alternative to oral iron for the treatment of iron deficiency anaemia (IDA) [216, 217, 218]. Allogeneic red blood cell transfusion has lifesaving potential in anaemic and haemorrhaging patients. However, a major limiting factor associated with this therapy is the risk of serious adverse events (transfusion reaction, transfusion transmissible disease, alloimmunization and immunomodulatory effect), costs and inadequacy [219]. Its use as an alternative in the management of iron deficiency is for treating critical anaemia (Hb level < 70 g/l), patients with acute myocardial ischaemia and in haemorrhaging patients who are haemodynamically unstable, patients in whom oral and IV iron is contraindicated or in cases of treatment failure nine [220]. Oral iron is a cheap and readily available option in managing patients with iron deficiency anaemia. Its use is however limited by challenge associated with gastrointestinal absorption and compliance [221]. Intravenous iron therapy, though slightly more expensive than oral iron is effective in managing patients with iron deficiency anaemia particularly when oral iron is contraindicated or ineffective [222]. Intravenous iron has the potential to reduce requirement for allogenic red blood cell transfusion [223]. The only limitations associated with the use of IV iron are adverse effects that have been associated with its use: risk of anaphylaxis, increased risk of infections, arthralgia, oxidative stress, hypophosphatemia, hypotension, headache, vomiting, chest tightness, fever, and hot flushes [224, 225]. Free iron has the potential to potentiate bacterial growth in vitro [226]. Intravenous iron therapy is effective in correcting iron deficiency anaemia (IDA) before any major surgery, and it can potentially reduce the need for allogeneic red blood cell transfusion and could help countries across the West African sub region better manage their limited allogenic blood stock for patients in whom oral and IV is contraindicated [227, 228, 229]. Oral and IV iron can have broad applicability to many patients particularly in low-income settings. There is need for more advocacy for countries in the West African sub region to promote the use of safe and affordable oral and IV iron more to manage patient with iron deficiency anaemia with the aim of reducing the need for limited allogeneic red blood cell transfusion.

3.4 Erythropoietin use can limit the dependence on allogenic blood across West Africa

Erythropoietin is a glycoprotein cytokine hormone synthesized in the kidney in response to tissue hypoxia. Its primary function is the stimulation of erythropoiesis (stimulate the division and differentiation of erythroid progenitor cells) in the bone marrow [230]. In patients with chronic kidney disease (CKD), there is damage to the kidneys and associated limited EPO production. Erythropoietin stimulating agents (ESAs) are recombinant versions of EPO produced pharmacologically via recombinant DNA technology. Examples of ESAs include epoetin alfa, darbepoetin, and methoxy polyethylene glycol-epoetin beta [231]. In patients with chronic renal failure, cancer, patients who are receiving dialysis, chemotherapy-induced anaemia and those with bone marrow suppression, the use of erythroid stimulating agents is clinically indicated in patients with haemoglobin less than 10 g/dL to increase haemoglobin levels and avoid the need for allogenic blood transfusions [232, 233]. Red blood cell (RBC) transfusion is an independent risk factor for cardiac surgery-associated acute kidney injury (CSA- AKI). Pre-operative administration of EPO may reduce the incidence of CSA-AKI, improve post-operative outcomes, decreasing the length of hospital and reduce the need for allogenic RBC transfusion in patients undergoing cardiac surgery [234]. Previous reports indicate that the administration of erythropoietin before cardiac surgery is associated with a significant reduction in the risk of exposure to allogeneic blood transfusion [235, 236, 237, 238]. There are several factors that limit the use of Erythropoietin stimulating agents particularly in low income developing countries; cost [2], its use is contraindicated in patients with hypersensitivity to non-human mammal-derived products [226], it has been shown to increase blood viscosity and may predispose high risk patients to DVT, pulmonary embolism and hypercoagulable state and should be used with caution in patients with history of ischaemic stroke or cardiovascular disease [227]. It is also contraindicated in neonates, peripartum mothers and breastfeeding mothers due to the risk for gasping syndrome in neonates (severe metabolic acidosis and associated gasping respirations, renal failure and neurological deterioration [228].

3.5 Autologous blood transfusion can facilitate the optimum utilization of limited allogenic blood across West Africa

Not all surgical patients require allogenic blood. Some can potentially benefit from autologous blood transfusion (ABT). Forms of ABT include predeposit autologous donation (PAD), acute normovolaemic haemodilution (ANH), and perioperative cell salvage (PCS) [239]. In PAD there is repeated preoperative phlebotomy, 4–5 weeks before surgery, during which time 4 or 5 units of in-date blood can be collected with ease. This technique reduces exposure to allogeneic blood. ANH involves a process where whole blood (1.0–1.5 l) is removed, and simultaneously intravascular volume is replaced with crystalloid or colloid, or both, to maintain blood volume. The anticoagulated blood is then reinfused during or shortly after surgical blood loss has stopped in reverse order of collection. The blood-sparing benefit of haemodilution is the result of the reduced red cell mass lost during surgical bleeding. Intraoperative RBC salvage entails the collection and reinfusion of blood lost during or after surgery. Shed blood is aspirated from the operative field into a specially designed centrifuge. Citrate or heparin anticoagulant is added, and the contents are filtered to remove clots and debris. Centrifuging concentrates the salvaged red cells, and saline washing may be used. This concentrate is then reinfused [239]. ABT is extremely safe, not associated with complications related to allogenic blood transfusion (immunological challenge associated with increase in tumour recurrence after surgical resection, increased postoperative infection rates, increased progression of HIV infection, blood transfusion reaction and multiorgan failure), crossmatching is not required; alloimmunization to foreign red cell antigen can be excluded and the fear of TTIs can be ignored [239, 240, 241]. Implementation of pre-operative autologous blood transfusion (PAD and ANH) and perioperative red blood cell salvage are strategies that can help countries in West Africa optimize the use of the limited blood stocks. Intraoperative red blood cell salvage is well recognized as a blood conservation strategy [242, 243] but it has limited applicability in critically ill patients. Postoperative recovery and transfusion of blood from sterile surgical drains in cardiac surgery has shown only marginal reduction in transfusion requirements. The feasibility and effectiveness of blood recovery techniques for other critically ill patients with acute blood loss are more limited. An autologous blood transfusion programme can be implemented as complementary to the established allogenic blood transfusion programme across the West African sub region. It has the potential to help the sub region conserve her allogenic blood stock for patients in whom autologous transfusion is contraindicated and result in more effective use of the limited allogenic blood supplies.

3.6 Implementation of restrictive red cell transfusion triggers

Anaemia is highly prevalent in critically ill and trauma patients. Two-thirds of these patients present with a haemoglobin concentration < 12 g/dl on admission and 97% of them become anaemic by Day 8 on admission [244]. Evidence has shown that critically ill patients with cardiovascular disease risk factors can survive with low haemoglobin than originally thought. Several studies have compared the use of lower haemoglobin thresholds as restrictive transfusion triggers in critically ill patients compared to liberal transfusion triggers. Hébert and Colleagues demonstrated that a restrictive transfusion strategy would reduce transfusion requirements and would be as safe as, and possibly better than, a more liberal strategy for critically ill adults [245]. Similarly, experience from a randomized controlled trial among paediatric ICU patients has shown that a haemoglobin threshold of 70 g/L, compared with a more liberal threshold of 95 g/L, reduced transfusion requirements by 44% [246]. Haemoglobin threshold of 70 g/L seems appropriate for critically ill adult and paediatric and adult patients [247]. Strong evidence exists that shows that a restrictive transfusion strategy with a lowered haemoglobin threshold is safe compared to a liberal strategy with higher haemoglobin threshold particularly in the absence of cardiovascular disease risk factors [248]. Evidence has shown that transfusion at higher haemoglobin thresholds is only beneficial in patients with acute myocardial infarction [249]. A major challenge associated with blood transfusion service delivery across the West African sub region is the challenge of safety and adequacy. Countries across the sub region will need to implement policies on restrictive transfusion triggers to facilitate optimum use of limited allogenic blood stock. Other evidence-based best practices the sub region needs to implement includes; reducing blood loss and the need for blood transfusions, improving the appropriateness of blood transfusion and implementing blood conservation strategies including the use of laboratory test (PT, APTT and fibrinogen) to determine bleeding predisposition in patients scheduled for surgery, evidence-based use of haemostatic agents [antifibrinolytic agents (aprotinin, tranexamic acid and epsilon aminocaproic acid), desmopressin and recombinant activated factor VII), the implementation of diagnostic endoscopy to reduce blood loss as well as maintaining normal pH, temperature and calcium levels to manage coagulopathy [250], blood salvage techniques, use of erythropoietin and use of indication coding or restrictive blood transfusion triggers. These implementations will help to limit the need for transfusion and enable the sub region effectively to manage her limited allogenic blood stock.

3.7 Availability and use of specialized blood products in the West African sub-region

The last 30 years has been associated with a significant development in the field of transfusion medicine particularly with the implementation of blood component therapy and the need to provide specialized blood products to facilitate the effective management of particularly patients with haematological malignancies [251]. Commonly prescribed specialized blood components include antigen negative red cells, gamma irradiated blood products, HLA and HPA matched platelets, washed red cells and CMV negative unit.

3.8 Antigen negative red cells

Red blood cell (RBC) alloimmunization is a significant challenge in blood transfusion practice. Red blood cell alloimmunization often results from antigen disparity between donor and recipient or between a mum and her foetus. The prevalence of alloimmunization ranges from 1 to 3% in the general population and 10–70% among TD patients [252, 253]. Other factors that play a role in the alloimmunization process include the immune competence of the recipient, the dose of the antigen to which the recipient is exposed, the frequency of exposure, antigen frequency in the population and the immunogenicity of the RBC antigen involved. Evidence-based best practice requires the implementation of a policy to carry out pre-transfusion alloantibody screen for all patients that require a red cell transfusion with the hope of detecting those that have atypical alloantibodies [252, 253, 254]. This implementation will facilitate the identification of the atypical antibodies and facilitate the indirect antiglobulin-based crossmatch of antigen negative red cells for the patient. Patients whose alloantibody screening test is positive should have a panel done to facilitate the identification of the alloantibody/ies present. This is to facilitate the crossmatch of units that have been phenotyped for the group specific antigen and found negative. The policy also recommends the provision of antigen negative units for patients in whom a clinically significant red cell alloantibodies was identified in the past but sub detectable in the current sample (alloantibody titre drops below detectable levels). The implementation of this policy is to ensure that the aim of giving the red cells transfusion is to optimize the haemoglobin level of the patients and by extension improve the oxygen carrying capacity or tissue perfusion in the recipient. It also reduces the risk of acute/delayed haemolytic transfusion reaction that can result when patients with a clinically significant alloantibody is transfused with donor unit positive for the group specific antigen. The national blood transfusion service should be able to test a percentage of all donations for Rh phenotype, K and other clinically significant red cell phenotypes such as Duffy (Fya) and Kidd (Jka) negative are generally in stock. Evidence-based best practice recommend that extended phenotyping be carried out for all transfusion-dependent patients (thalassemia, sickle cell disease and myelodysplastic syndrome) who are chronically transfused for Rh (C, c, E, e) and Kell antigens before the initial RBC transfusion [255]. This is to ensure that they are transfused at least ABO, Rh (C, c, E, e) and Kell compatible units as a minimum [256, 257, 258]. The use of uncrossmatched O red cells can have a lifesaving potential in haemorrhaging patient when there is no time to carry out a full pre-transfusion testing. Blood group O negative units used in emergency for a woman of childbearing age should be rr (C-, D- and E-), K, CMV and High titre negative [259]. In many settings across the West African region red cell phenotyped for clinically significant red cell antigens are not readily available. Donors are tested for only the ABO and Rhesus D group. Many hospitals in the sub region do not routinely test patients requiring a red cell transfusion for the presence of alloantibodies and facilities for panel testing to identify the alloantibodies present are often not available. Countries across the sub region must implement best practices to prevent RBC alloimmunization and haemolytic transfusion reactions (HTRs) including routine testing of all patients that require a transfusion for the presence of alloantibodies, provision of extended phenotyping for all transfusion dependent patients, optimization of the method and scope of RBC antigen typing as well as the selection of antigen negative blood for crossmatch to facilitate the provision of timely, most compatible and safe blood for transfusion to patients.

3.9 Gamma irradiated blood products

Transfusion-associated graft-versus-host disease (TA-GvHD) is a rare, usually fatal, complication of transfusion that occur when the viable and potent lymphocytes in the donor engraft and destroy the host lymphocytes and by extension the host immune system. TA-GvHD can either occur when immunocompromised recipients are transfused with cellular blood components containing viable lymphocytes or when a recipient receives blood components from a human leucocyte antigen (HLA)-haploidentical unrelated donor or from their family member. Transfusion of potent donor (related and non-related) lymphocytes to HLA haploidentical recipient is documented as the most potent risk factor for the development of TA-GvHD [260]. The transfusion of pre- storage leuco depleted blood products can reduce the risk of TA-GvHD. In the developed world all transfused units are universally leucocyte depleted. The implementation of this best practice has brought about a significant reduction in the residual cases of TA-GvHD. A previous report reported a TA-GvHD prevalence of 18·9% (66 out of the 348) between 2000 and 2013 [261]. Irradiation by exposing donor blood products to irradiation using Gamma rays and X-rays (a minimum of 25 Gy) is the principal of inactivating lymphocytes in the transfused component. Transfusion of washed red cells is not as effective in preventing TA-GvHD as irradiation. Gamma irradiated blood product is clinically indicated in the following patients groups; foetus and neonate who are immunological immature and whose lymphocytes are naive, patients needing intrauterine blood transfusion (IUT) including those requiring routine ‘top-up’ neonatal transfusions following IUT [262], recipients of allogeneic HSCT, adults and children with Hodgkin’s Lymphoma (HL), patients treated with purine analogues (fludarabine, cladribine bendamustine and pentostatin) which are known to induce profound lymphopenia with associated low CD4 counts, CLL patients treated with alemtuzumab, aplastic anaemia patients undergoing treatment with ATG or alemtuzumab and patients receiving ATG or other T-lymphocyte-depleting serotherapy for rare types of immune dysfunction) [263, 264, 265, 266]. The median time from transfusion to presentation among TA- GvHD patients is 11 days and commonly associated symptoms include rash (80·2%), fever (67·5%), elevated liver enzymes (66·4%), pancytopenia (65·2%), diarrhoea (43·1%), bone marrow aplasia (22·7%) and hypocellularity (17·2%) and hepatomegaly (13·5%). Laboratory information management systems (LIMS) should be updated with relevant information for patients in whom gamma irradiated blood products are clinically indicated. Evidence-based best practice in the management of patients in whom irradiated blood products are indicated requires the following; effective communication among those involved in the care of these patients (clinical areas and transfusion laboratories) as well as between transfusion laboratories particularly during patient transfers from one hospital to another and carrying of treatment information cards to facilitate the provision of appropriate components [267]. In emergency situations, where non-irradiated components are unavailable and where delay in sourcing gamma irradiated red cells or platelets can be life- threatening, leuco depleted blood or platelets can be sourced promptly as a minimum requirement. The justification for this must be included in the patient case note and such a patient should be observed for possible evidence of TA-GvHD for few weeks. Many of the above best practices are not readily available in blood centres in the sub-region. There is urgent need for the implementation of gamma irradiated products for patients in whom gamma irradiated red cell, platelet and granulocyte components is clinically indicated across the West African sub region as a way of optimizing the transfusion service delivery in the sub region and reduce the risk of TA-GvHD.

4. HLA and HPA matched platelets

Platelets are anucleate cellular elements that play a role in haemostasis. Platelet concentrate is used to manage thrombocytopenic patients with haematological oncological disorders including the management of haemorrhaging patients. Platelet can be transfused either as apheresis platelet concentrate (APC) or pooled platelet concentrate (RPC) [268]. The absolute clinical indications for apheresis platelets include patients who require HLA compatible and/or HPA matched platelets (platelet refractoriness due to the presence of HLA and/or HPA antibodies), patients with neonatal alloimmune thrombocytopenia (NAIT) and patients who require IgA deficient platelets. Apheresis derived platelets concentrate are associated with a lower risk of alloimmunization and subsequent development of platelet refractoriness, the risk of TTIs is less because the recipient is exposed to a single donor. Also, the platelet yield from apheresis is about 6 times more in pooled platelets [269, 270, 271, 272]. The cost of producing platelet concentrate is higher with apheresis compared with pooled platelets. Also, the risk of allergic adverse reactions is about four times higher with apheresis derived platelet concentrate [273]. Other aspects may impact the decision: the fact that using APC in place of RPC reduces the total donor exposure of patients was considered critical in some countries to reduce the risk of transmission of blood transmissible disease. Finally, the cost of the components, much higher for APC, may be considered. Platelet refractoriness is a term used to describe the failure to achieve an adequate increase in platelet count of a recipient after two consecutive transfusions of random platelets. The common cause can either be immunologic (HLA - class I specific antibodies, HPA - antibodies or ABO - antibodies – mediated resulting from the transfusion of ABO incompatible platelets to a recipient who is positive for high titre anti-A or anti-B haemolysin) or non-immunologic (platelet sequestration and consumption) in nature resulting from non-immune destruction of transfused donor platelets [273]. Alloimmunization to human leukocyte antigens (HLA) class or human platelet antigens (HPA) can result in platelet refractoriness [274]. Patients with these anti-leucocyte or platelet antibodies will need to be provided HLA class I and HPA compatible/matched platelets [275, 276]. Refractoriness to platelet transfusion is usually caused by alloimmunization to either HLA/platelet antigens or as a result on non-immune destruction of platelets and is commonly seen in 14% of haematology patients receiving platelet transfusions with HLA alloimmunization as a major cause [277, 278]. Alloimmunization to HLA/platelet antigens and by extension platelet refractoriness can be reduced by transfusion of leucodepleted products, use of irradiation or transfusion of HLA/HPA matched platelet transfusions [279, 280]. Despite the importance of platelet concentrate in the management of thrombocytopenic haematology, oncology and haemorrhaging patients, the product is seldom available in most settings across the sub region. Government of West African states will need to show more commitment to the provision of a quality blood transfusion service by investing significantly in transfusion-related infrastructure with the hope of achieving improvement in transfusion service delivery.

4.1 Washed red cells

Washing of red cells is often carried out for three major clinically relevant reasons; to reduce the amount of cytokines [causes of febrile non-haemolytic transfusion reactions (FNHTRs), reduce the level of allergen proteins to reduce the risk of allergic reactions resulting from contaminating plasma proteins (including IgA) as well as to reduce the concentration of potassium that leaked from the intracellular during storage to reduce the detrimental effect of hyperkalaemia in the recipient [281]. Patients who are IgA deficient run the risk of developing allergic reaction if they are transfused with IgA- rich donor blood. Washing can potentially remove a significant 90–95% plasma resulting in a significant reduction of the IgA content to <0·05 mg/dl IgA –a level common seen in IgA deficient patients. Washed leucodepleted red cells reduce the risk of alloimmunization to HLA. Washing is often performed by normal saline (0.9% NaCl) in either an open or a closed system. RBCs washed in an open system should be used within 24 hours (prevent bacterial contamination) of washing while that washed in a closed system have a shelf life of 14 days post washing [282]. Red cell washing increases the RBC osmotic fragility and increased haemolysis post transfusion [283]. Washed red cells are associated with less systemic inflammation and lower levels of free plasma haemoglobin with its nitric oxide scavenging property which has been shown to be independent predictor of mortality in septic patients [284].

4.2 CMV negative unit

Cytomegalovirus (CMV) infection is endemic globally. In the USA the seroprevalence of the disease range from 30 to 97% [285]. Cytomegalovirus (CMV) is a significant contributor to increased morbidity, mortality and cost of management of immunocompromised patients [286]. CMV is a highly contagious viral infection that is transmitted through close contact with bodily fluids (blood, saliva, urine and breast milk). CMV can also be transmitted by organ transplantation and blood transfusion, when the donor is CMV positive, and the recipient is CMV negative [287]. Common signs and symptoms associated with the disease include; fever, malaise, leukopenia and neutropenia. Immune-deficient individuals can suffer severe or even fatal disseminated infections. Evidence-based best practice in the developed economies recommend that the following patient’s groups should be transfused with CMV negative cellular blood products, congenital immunodeficiency and HIV-infected patients, haematopoietic progenitor cell transplant recipients, low birth-weight infants, pregnant women till delivery and their foetuses (to prevent congenital CMV), severely immunosuppressed patients and recipients of solid-organ transplant recipients [288]. The risk of CMV transmission through blood transfusion can be prevented by two major ways; by transfusing vulnerable CMV naïve and profoundly immunocompromised with blood and blood products that are negative for CMV and by ensuring that cellular blood products are universally leucodepleted (fewer than 5 × 10⁶ leukocytes per unit) [289]. CMV negative blood and components is critical to reducing the risk of transfusion- transmitted symptomatic CMV infection in recipients who are themselves CMV naïve. Other potential measures that can reduce the risk of transfusing CMV infected blood products include washing red cell units and removing the buffy coat, freezing, thawing and subsequent deglycerolizing. The major drawback associated with these measures include the fact that they are not practicable large scale and are associated with a significant cost implication [288]. The implementation of TT- CMV reduction strategies in the late 1980s requiring that seronegative marrow recipients and other high-risk groups receive CMV seronegative blood products has brought about a significant reduction in the risk of CMV infection from 28% -57 to <5% [290, 291]. Government of West African countries have a duty of care to implement CMV prevention strategies by ensuring that evidence-based best practices requiring that all cellular blood products transfused across the sub region are universally leukocyte reduced and screened serologically for CMV.

4.3 Optimizing safe blood donation in the West African sub-region

The two major challenges associated with blood transfusion service delivery across the West African sub region are access to safe and adequate supply of blood and product products [2, 292]. World Health Assembly resolutions WHA28.72 [293] and WHA58.13 [294] urge member states to develop national blood transfusion services based on VNRDs. A VNRD-based NBTS is key to sustained supply of safe and adequate blood and blood products. It is the only realistic way to ensure long-term and consistent supply of blood and blood products to eliminate the chronic shortage of safe blood and blood products particularly in low- and medium-income countries. Not only is blood donation level low in the West African sub region, but it is also predominantly family replacement donor-based rather than benevolent, non-remunerated donors (VNRBDs) who give blood out of altruism. The blood donation rate in sub-Saharan Africa is significantly lower (4–5 per 1000 population) compared to the developed economies (30 donations per 1000 population). WHO recommends that blood transfusion from regular VNRBDs have the lowest risk of TTIs. There are several factors militating against the low VNRBD levels in most West African countries: lack of organization and financial resources, but also, to some extent, of socio-cultural barriers such as limited levels of education, religious and mystic beliefs and misconceptions about blood use [295]. Voluntary, non-remunerated blood donation is the cornerstone of a safe and adequate national blood supply that meets the transfusion requirements of all patients. VNRBDs represent less than 50% of whole blood donations in low-income countries compared with 76–100% in high-income countries [296]. The low VNRBD levels in the sub region can be attributable to several reasons: lack of organization and financial resources, socio-cultural barriers, low levels of education, religious and erroneous beliefs and misconceptions about blood donations [297]. Government across the West African sub region must implement innovative ways to recruit and retain voluntary donors; celebration of the gift of blood donation from voluntary blood donors; increasing public awareness of voluntary non-remunerated blood donation; educating the public on the importance of regular, voluntary, non-remunerated blood donation; educating the public on the benefits of voluntary non-remunerated blood donation to recipients; promoting healthy living (nutrition, exercise, lifestyle); and provision of noncash incentives to encourage people to donate blood.

4.4 Implementation of cell-free foetal DNA testing across the West African subregion

Haemolytic disease of the foetus and newborn (HDFN) is an alloimmune disease associated with alloantibody developed by the mum triggered by a previous incompatible blood transfusion or a transplacental haemorrhage during a previous pregnancy associated with foreign red cell antigen entering the maternal circulation and sensitizing her to produce alloantibody. These alloantibodies, being low molecular weight antibodies can pass through placenta in subsequent pregnancy involving a foetus with a red cell antigen to which the maternal alloantibody is specific. This maternal alloantibody usually will cross the placenta barrier into the foetal circulation and coat the foetal red cell containing the group specific antigen and induce haemolysis. The disease often results from maternal immunological incompatibility with foetal blood groups leading to the production of alloantibodies. The rate of antibody production depends on the red cell antigen dose that enters the maternal circulation, the immune competence of the mum and the immunogenicity of the foetal antigen [297]. Clinical presentation of the disease ranges from asymptomatic mild anaemia to hydrops foetalis or stillbirth resulting from severe anaemia and jaundice. Management options include; the use of amniocentesis (an invasive procedure to obtain amniotic fluid which is analysed for product of haemoglobin breakdown to identify the severity of the disease), serial Doppler ultrasonography measurements to diagnose foetal anaemia, in utero, intrauterine transfusion, titration and quantification of alloantibody level, controlled early delivery, top up transfusion and exchange transfusion in the management of severely alloimmunized foetuses [298, 299]. Anti-RhD is the most incriminated alloantibody responsible for the majority of HDFN. However, the availability and widespread implementation of antenatal and postpartum Rhesus immune globulin prophylaxis particularly in the West has resulted in a marked decrease in the prevalence of alloimmunization to the RhD antigen among pregnant women. Other commonly encountered antibodies include anti-c, anti-K, E, AB0, JK (Kidd), and FY (Duffy) [300]. The most important blood groups are D, c, E, and K with respect to antenatal foetal blood group determination using cell-free foetal DNA (cfDNA) [301]. cfDNA derived from the foetus circulates in maternal blood. cfDNA testing is a non-invasive prenatal screening carried out on maternal plasma of pregnant women to predict foetal blood groups with the aim of; assessing the risk of haemolytic disease of the foetus and newborn (HDFN) in previously alloimmunized women and also to determine the Rhesus D group of the baby in order to determine if a non-previously immunized mum will need to be recruited into the RAADP program and will require anti-D prophylaxis following a potentially sensitizing event during pregnancy [302]. The cfDNA test can help identify women who have red cell alloantibodies and may be affected by haemolytic disease of the foetus and newborn (HDFN). cfDNA testing is carried out on maternal blood and can predict the foetal RhD, RhC, Rhc, RhE and K status of the foetus and by extension the risk of HDFN [303]. Early in pregnancy, small amounts of foetally derived cfDNA exist, but the fraction of foetal cfDNA in the maternal circulation increases with advancing gestational age [304]. The clinical implementation of this technology should be encouraged across the West African sub region. There are many advantages associated with this implementation [305, 306]. The test is significantly sensitive and specific with diagnostic sensitivity ranging from 95 to 100% and specificities over 99% [307, 308, 309]. The prevalence of Rh D negative varies widely between Caucasians with a prevalence >14% [307, 308, 309, 310] compared to ethnic groups of sub-Saharan Africa with a prevalence ranging between 2.4 and 4.5% [311]. Evidence has shown that 40% of Rhesus D negative women carry D Negative foetuses. It is evidence-based best practice that all Rhesus D negative pregnant women who are not previously immunized are universally offered anti-D prophylaxis at the 3rd trimester under the RAADP program. NICE guidance released in 2008 recommend that a single dose of anti-D (1500iu) given to Rhesus D negative not previously sensitized pregnant women between weeks 28 and 30 would also be cost-effective in potentially preventing anti-D HDFN in subsequent pregnancy [312]. The use of cfDNA testing for the determination of the predicted Rh D group of the foetus has several advantages; allow for the rational implementation of antenatal immunoprophylaxis for women in whom it is not clinically indicated who are predicted to be carry Rh D negative foetus rather than providing the prophylaxis universally to all Rh D negative non-previous immunized women. cfDNA testing can potentially predict 40% of these women who are carrying D negative babies for which Rh D prophylaxis will be a waste of a scarce human resource [313, 314, 315, 316]. Also, the feto-maternal haemorrhage testing carried out during a potentially sensitizing event during pregnancy and post-delivery will not be required (reagent and time to carry out the testing) if the baby is predicted to be Rhesus D negative. The prophylactic anti-D offered to these Rh D negative women is a human blood product with reduce potential to transmit hepatitis C and prion type diseases [317]. The women whose babies are predicted to be Rhesus D negative with will be spared the pain and associated cost of travel to hospital to receive the anti-D prophylaxis [318]. Government across the West African sub region will need to live to their responsibility by implementing evidence-based best practices; cell-free DNA testing, provision of anti-D prophylaxis for non-previously sensitized Rh D negative women, feto maternal haemorrhage testing, non-invasive serial sonograms with Doppler of the Median Cerebral Artery (MCA) to determine the peak systolic velocity (PSV) and by extension foetal anaemia, amniocentesis and provision of blood that meet the minimum requirement for intrauterine transfusion for foetus severely affected with HDFN in utero and facility for sonographic guided intrauterine transfusion through the umbilical vein should be implemented across the sub region to optimize the obstetric and neonatal care offered.

4.5 Quality management issues in blood transfusion service delivery in West Africa

Blood transfusion process comprises a series of steps ranging from ordering of blood or blood products, administration, monitoring of the transfused patient, managing of adverse reactions and events as well as documentation of transfusion adverse events and outcomes [319]. Quality management in blood transfusion is the sum of all the processes put in place to ensure that blood products and services are produced consistent, safe, efficacious service that meet the need of the customers [320]. There is increasing advocacy to ensure the efficacy, quality and safety of blood and blood products. The sum total of all the processes in place to ensure safety of blood and blood product from the point of collection of blood and blood products from blood donors to the point of administration to the recipients [321]. Quality management in blood transfusion encompasses the organization and her quality management system, personnel and organization, quality policy, organograms with responsibilities of staff, job description for staff members, change control of documents, continuous training based on SOPs (should be approved before distribution and the correct versions should be provided at the points of use), collection of blood and blood components, non-conformance, deviations, complaints, recall, corrective and preventive actions, self-inspection, audits, and improvements [322, 323]. The blood transfusion organization must ensure that they understand and meet the current and future requirements of the customers. The Blood Service must ensure that adequate resources are provided to implement and operate the quality management system, to continually improve its effectiveness and to satisfy customer requirements. The physical resources (equipment, consumables, work areas and utilities) to undertake the work must be suitable to attain the required standards.

4.6 Personnel and organization

It is a general requirement that all personnel responsible for blood transfusion service delivery should have the right skills, experience, education/training, certification, competence and regularly trained and retrained [324]. It is expected that appropriate staffing levels involvement should ensure the safe and effective delivery of all transfusion service activities and be subjected to annual review [325]. All personnel shall have up-to-date job descriptions that clearly set out their tasks and responsibilities. Blood transfusion organizations shall have separate persons as training officer and quality manager. Provision of training to the personnel on safe blood transfusion, hazards, and appropriate implementation of corrective and preventative measures, as well as abiding with standard safety guidelines are vital and must be implemented throughout the entire blood transfusion process [326]. In every step in the blood transfusion process there are potential risks, such as errors in patient identification, blood typing, cross-matching, administration and other human errors. Many errors which result in serious morbidity or mortality that occur in the blood transfusion process and by extension in healthcare delivery are related to human error with training and competency issues a major contributory factor [327, 328]. All personnel should be appropriately trained, and their competency assessed before being allowed to work unsupervised. The contents of training being implemented should be periodically assessed and the competence of personnel evaluated regularly. Employers must develop personal development plan (PDP) for all staff involved in the blood transfusion process that ensures that staff develop in a continual format to enable the delivery of a continually improving quality service tailored towards meeting the present and strategic future needs of the organization and her customers. Personnel are required to participate in a lifelong continuing professional development (CPD). There is also the need to ensure that transfusion staff are adequately remunerated. Efforts should be made to employ, motivate and retain the best staff, adequate number of staff and mix as well as ensuring that there are opportunities for professional growth and development and that staff are not working excess unsocial hours with inadequate recovery time. Previous report indicates that these issues can affect staff turnaround, result in burn out, low morale, high sickness absences, increased error rate, poor team spirit, diminished productivity, and suboptimal blood transfusion service delivery [329]. The healthcare delivery system in the West African sub region faces many challenges including human resource inadequacy. Migration of health workers (brain drain) defined as the movement of health personnel in search of a better standard of living and life quality, higher remuneration, better working condition, wellbeing, access to advanced technology and more stable political conditions has made the human resource challenge in the sub region even worse [330]. The best of West African human resources in healthcare who should be offering excellent care to citizens in their home nations have emigrated to developed countries. The physician-to-population ratio is estimated to be 13/100,000 in Africa, compared with 280/100,000 in the United States [331]. Although there is a hypothesis that brain drain could be beneficial and impart positively on medical education fostering international collaboration in healthcare research and development [332]. This argument will only be substantive if these health professionals return periodically or permanently after practicing abroad for a while. The economic effect of brain drain on the economy of developing countries is huge [333]. There are several reasons for the poor retention of healthcare workers in the West African sub region: poor remuneration, lack of opportunity, high unemployment in health labour markets and the deplorable state of healthcare infrastructure in the sub region. Leaders of West African countries must take realistic steps to ensure that all staff involved in blood transfusion service delivery across the sub region are adequately trained, remunerated, motivated, and retained to ensure high morale, increased productivity and to prevent the risk of brain drain. These have the potential to reduce the reduce the error rate, brain drain and suboptimal blood transfusion service delivery.

4.7 Premises and environment

The premises and environment where all processes involved in blood transfusion delivery is implemented must be enabling and must be conducive for activities being carried out. The work environment (processes, systems, structures and tools or conditions) in the blood transfusion workplace that can potentially impact the staff favourably and by extension their performance and productivity should be provided [334]. The work done must be process oriented, associated with effective cleaning and maintenance protocols, and arranged in such a way as to minimize the risk of errors, injury and to minimize the risk of contamination. There should be a separate area (Donation, testing and processing, storage and waste management) that is optimally endowed (human and materials). Donation area should be endowed with facilities to allow for confidential interviews and assessment of individuals to determine their eligibility to donate blood. Collection area should be appropriately equipped to facilitate the safe collection of blood and blood products as well as manage adverse reactions or injuries from events associated with donation. The safety of the transfusion staff and donors must be maintained. The environment where the blood transfusion process is implemented must be enabling in terms of space, safety and infrastructural endowment (equipment, availability of piped borne water, soap, appropriate sanitation facilities, handwashing facilities, availability of adequate infection control measures including personal protective equipment (PPE) and waste management as well as availability of uninterrupted power supplies) [335, 336, 337]. The blood transfusion organization should have a dedicated laboratory for donor testing and should be separated from the processing areas to prevent the risk of contamination. There should be restricted access (limited to authorized staff) to the testing and processing areas. There should also be a dedicated storage area for the blood components (red cells, plasma, and platelets). There should be an area set aside for the secure and segregated storage of different blood components including a separate area for quarantine (not fit to use) and released (fit to use) as well as blood products collected for dedicated use (autologous donation) [338]. The storage area must have access to uninterrupted power supply and back up fridges, freezers and alternative sources of power in the event of equipment or power failure. Provision of adequate and safe blood transfusion service delivery is associated with the generation of waste which is potentially hazardous and may carry a potential for infection and injury [339]. Suboptimal and inappropriate handling of healthcare-related waste can have serious public health consequences and a significant impact on the environment [340]. The blood transfusion organization should have a system for the effective management of waste. The waste generated during production of blood and blood component carries a higher potential for infection and injury. Waste generated should be segregated [domestic non-hazardous, hazardous healthcare waste including sharps (needles, hypodermic needles, scalpels, blades, lancet, infusion sets, broken glass and pipettes) and chemical and radioactive waste] and disposed appropriately. In most West African countries, unsustainable management of waste is common. Open dumping and open burning are commonly implemented as waste treatment and final disposal systems. Illegal dumping of waste onto sidewalks, open fields, storm water drains and rivers is commonplace with negative economic, social and environmental impacts. Also, waste management involves the activity of the informal sector including waste pickers and scavengers with a significant associated health risks from potentially hazardous waste [341]. There is need for the implementation of effective waste management across the West African sub region by taking realistic steps at waste reduction, reuse if safe, recycling, recovery and treatment to achieve sustainable and environmentally sound management of all wastes [342, 343].

4.8 Equipment and materials

All equipment for use in the blood transfusion organization must have Equipment Operating Procedure (EOPs), be validated prior to implementation, regularly calibrated, and maintained [343]. The acquisition of any equipment must be justified and constitute value for money and should be carefully chosen to minimize any hazard to the blood donors, the personnel, or the blood components itself [344]. The transfusion organization must carry out validation of equipment, certification and pre-acceptance testing of all reagents to establish that the performance characteristics of the method meet the requirements for the intended analytical application. Validation is a pre-defined exercise to confirm that equipment or a procedure (either current or proposed) is fit for its intended purpose and meets its pre-defined specification. The benefits of validation include assurance that critical aspects of a process are in control, increased probability of uniform product quality, reduced product waste and reduced customer complaints. Reagent certification of reagents ensures that reagents are performing to the quality standards of the manufacturers and fit for diagnostic work. Only reagents and materials from approved suppliers that meet the documented requirements, certification and specifications shall be used. The blood organization should have a robust computerized LIMS with back-up procedures. The LIMS should be validated before use [345]. All the associated hardware and software shall be protected against unauthorized use and changes. The back-up system must prevent loss of or damage to data [346]. The blood transfusion organization should implement a documented change control process that facilitate the suggestion of changes to the process by staff involved in the process that is beneficial, potentially save cost, remove bureaucratic aspects, and will optimize the safety of donors and personnel. The change control is planned and implemented in a controlled way, the possible re- training for staff involved in the process following the standard operating procedures (SOPs), shall ensure there is a record of the processes operated before and after the change, that the date of the change is known, and that material processed through the changed system can be identified. There should also be a system to ensure that the effectiveness of the newly implemented process is monitored and opportunities for further improvement are investigated and, where relevant, implemented. It shall support the organization in trying to learn from incidents, accidents, near misses, complaints, and other event information. The objective analysis of these and implementation of corrective and preventive measures in an action-planned format will facilitate the delivery of a continually improving quality blood transfusion service across the West African sub region [347, 348].

4.9 Recall and traceability

Effective blood transfusion service delivery requires that a system be in place to allow 100% accountability of donated blood and blood products [349]. The implementation of traceability facilitates the easy and prompt recall of products that is identified to be suboptimal or have potential to cause the recipient after release from the national blood transfusion service to hospital blood bank or from the hospital blood bank to the ward or satellite fridges can be recalled [350]. The recall system should be such that it is prompt and can be triggered at any time. All recalled products should be separated and kept away from other units that are fit for use to prevent its accidental release until a decision is made on the final fate (release to the pool or discarded). The recall process should be reviewed regularly to ensure its continued effectiveness. Most countries, particularly those in developing countries were poorly implementing sub-indicators of haemovigilance particularly in the area of legal provisions, arrangement for effective organization and human resources indicators [351]. There must be a system to ensure that materials can be traced through the entire process from procurement, testing, production, issue from the NBTS to the hospital blood bank and subsequently to the recipient. There must be 100% traceability for all donated units (who donated the unit, when the blood was released to hospital blood bank and when unit was transfused to the recipient or discarded). For all donated units, traceability must be maintained from vein to vein from donor to the patient. In Morocco for example, the traceability rates were around 51% in Casablanca [352] and 15.5% in Rabat [353].

5. Ensuing a continuous quality improvement-oriented blood transfusion service across the West African sub-region

The blood transfusion organization must strive for Continuous Quality Improvement (CQI) by the regular and objective evaluation of overall performance using indices such as incidents, errors, near misses, complaints, audit and accreditation (internal and external), litigation and customer satisfaction surveys to determine the quality of service delivered on a continual basis [354]. At the root of CQI is culture of root cause analysis as a problem-solving tool to identify nonconformities with the hope of identifying corrected and preventive actions (CAPA) that needs to be implemented in an action planned format (what is to be done, why, how, by whom and time frame to achieve the task) to nip the non-conformance in the bud. All complaints from the customer and other relevant information, including any serious adverse reactions and serious adverse events lined to a defective blood component should be reported, documented, and promptly investigated to identify the causative factor/s of the defect and promptly recall the affected unit if necessary [355]. All serious adverse reactions or serious adverse events should be reported to appropriate regulatory authorities.

5.1 Quality audit and accreditation

A Quality audit is a planned systematic, independent and documented process of evaluating elements of a quality management system. It assesses whether quality activities and related results comply with planned arrangements [356]. Audits can either be internal or external and ensure that process are being operated as stated in the SOP and that procedures and associated quality assurance comply with Good Manufacturing Practice (GMP) principles. Audits should be carried out by a competent and trained individual who is knowledgeable about the process. The results of all audits and all non-conformances identified should be documented to allow for the implementation of root causes and action-planned implementation of corrective and preventive actions in a timely manner [357]. Unlike their Western counterparts, many countries in the West African sub region do not have a fit for purpose, centralized and coordinated blood transfusion services and the safety, quality, efficacy and regulatory framework remain significantly poor. The implementation of quality management system in blood transfusion across the West African region is relatively naïve. The issues surrounding the safety of production, supply, distribution, administration, and clinical use is poorly developed. Blood transfusion service delivery across the West African sub region can be optimized. Audits of practice and incident reporting to national haemovigilance schemes have shown that poor hospital transfusion practice is frequent and occasionally results in catastrophic consequences for patients [358]. There is the need for governments of countries in the sub region to take steps to ensure the implementation of a quality management system-oriented blood transfusion process across the sub-region. Quality efforts should be made to ensure that blood transfusion is efficacious by the objective implementation of a high level of quality and safety throughout the transfusion chain (blood collection, testing, processing, storage, distribution, matching, delivery and clinical use of the blood products.

5.2 Providing safe blood transfusion across the West African sub-region

Blood transfusion is an indispensable component of modern healthcare delivery and saves millions of lives annually. Blood transfusion is often required to manage anaemia, bleeding following trauma, intra and post- operative, obstetric haemorrhage (ante and post-partum) and to manage several medical diseases including haematological conditions [349]. For blood transfusion to have life- saving potential, it must be safe. Safe blood transfusion is the right blood collected from the right voluntary non remunerated donor and transfused to the right patient at the right quantity, at the right time, in the right place and based on the right clinical indication [359]. Safe blood transfusion is not wishful thinking. It is achieved by implementing evidence-based best practices in key areas including patient identification, documentation, communication, patient consent, request for transfusion, pre transfusion sampling, collection of blood and delivery in the clinical area, safe administration of blood and monitoring during a blood transfusion. A significant number of patients worldwide are administered with wrong blood annually with sometimes fatal consequences. Many of these incidents are preventable and predominantly due to human errors [360]. The common root causes of these errors are poor patient identification, misidentification of patient during pre-transfusion sampling, errors during laboratory testing, error during collection of blood from the blood bank and errors during blood administration. Previous report indicates that as many as 40% of mis transfusions are due to errors in the post-analytic phase: often failures in the final check of the right blood and the right patient at the bedside [361]. There is need for healthcare professionals involved in the blood transfusion process including biomedical scientist, medical doctors and nursing staff practice in environments that recognize the importance of reducing error and improving safety using non-punitive system approaches that encourages the reporting and objective investigation of incidents, accidents, near misses and errors [362, 363].

5.3 Patient identification

Positive patient identification is fundamental to safe blood transfusion. It is essential to ensure that the right blood is given to the right patient. Patient misidentification can have a potentially fatal consequence for patients [364]. Errors in the whole-blood transfusion chain - from initial recipient identification to final blood administration - occur with a frequency of approximately 1 in 1000 events [365]. Among pre-analytical errors, misidentification and mis transfusion are still regarded as a considerable problem, posing serious risks for patient health and carrying huge expenses for the healthcare system [366]. Patient identification errors in pre- transfusion blood sampling (‘wrong blood in tube’) are a persistent area of risk in blood transfusion errors [367]. Evidenced best practice in the West requires that all patient for which blood transfusion is intended wear an identification band containing the minimum patient identifiers (surname, forename, date of birth and hospital number) to facilitate an unmistakable patient identification during pre-transfusion sample collection and during blood administration. In accident and emergency units, patients presenting in coma who cannot be immediately identified must be given at least one unique identifier (A&E or trauma number and patient gender). Prior to collecting or administering blood to a patient, the patient, carer or parent in case of children should be requested to state their full name and date of birth and this information must be compared to what is on the patient wrist band. It is only when there is a match that a patient is said to have been positively identified for sample collection and administration purposes. All identification discrepancies at any stage of the transfusion process must be investigated and resolved before moving to the next stage to prevent transfusion errors.

5.4 Documentation

In blood transfusion the golden rule is that anything not written down was done. Blood transfusion documentation is critical to ensuring 100% traceability of all donated donor units. Documentation (hard copy or electronic) to capture events at every stage of the transfusion process (pre-transfusion, during transfusion and post transfusion) should be kept in a clear, legible, readable, auditable, and user-friendly format. Vital information including transfusion prescription sheet, crossmatch worksheet, temperature, monitoring records, reagent storage, equipment validation, reagent certification and monitoring charts must be kept providing a clear audit trail [350]. Previous report indicates that use of barcode reader and related electronic technology can be adapted to improve transfusion safety and reduce the risk of human errors at all steps of the blood transfusion process [368]. All transfusion documentation should include the minimum patient identifiers (name, date of birth and hospital number). Pre-transfusion related information including laboratory data and clinical indication for transfusion, information that the potential risks, benefits and alternatives have been discussed with the patient and that written informed consent was obtained, the dose/volume and rate of transfusion and information of any special transfusion requirement for the patient such as CMV negative, antigen negative blood, gamma irradiated components, etc.). Previous report indicates that bedside ABO-typing and checklist prior to blood transfusion can control the ABO-mismatched transfusion if done timely and correctly [369]. Intra transfusion documentation must contain vital information; medical staff who started the transfusion, date and time transfusion commenced and completed, details of blood component (component type, bag numbers and any special requirement) as well as information on observation prior, during and post transfusion (temperature, blood pressure, respiratory rate and pulse). Post-transfusion documentation must include information on clinical outcome of any transfusion, adverse reaction or events and evidence that transfusion was beneficial and accomplished the desired outcome (HB optimization and improvement in anaemia and related symptoms) [370]. Previous report indicates that training and education of health-care staff on transfusion-related documentation at the bedside is vital to reducing blood transfusion related errors, morbidities, and mortalities [371].

5.5 Communication

Communication (verbal and written) between clinical, laboratory staff and porters should be clear and unambiguous as it is critical to patient safety. Misunderstanding and transcription error are common communication- related issues associated with transfusion errors. Effective commination among the healthcare care workers involved in the blood transfusion process is critical to limiting transfusion-related errors [372]. Written or electronic communication should be used wherever possible with request for urgent transfusion supplemented by telephone request with laboratory staff. Good communication is especially important at times of staff handover between shifts, both on the wards and in the laboratory, and can be enhanced by a standardized and documented process. Handovers should be built into transfusion laboratory routine practices, ensuring effective transfer of information and appropriate follow up actions are taken [373]. Hospital transfer of patients is common- place in healthcare delivery. Effective transfer of relevant transfusion information relating to patient care is vital in blood transfusion service delivery [374].

5.6 Patient consent

Under the principle of medical ethics, a competent patient’s autonomy and right to determine his or her treatment is widely recognized in medical practice. Evidence-based best practice recommends that patients are informed about and understand the purpose, benefits and potential risks of transfusion as well as available alternatives. The Advisory Committee on the Safety of Blood, Tissues, and Organs (SaBTO) recommends that ‘valid consent’ for blood transfusion should be obtained and documented in the clinical record (signed consent) [375]. Blood transfusion is not an entirely safe form of treatment. It is sometimes associated with adverse effects and events. Blood transfusion must not be given lightly but rather it must be given only when there are no safer alternatives. Its use must not only be based on laboratory results alone but also on the clinical presentation and presence of symptoms. The potential risk, benefits and alternatives must be discussed with patients to enable them to make an informed decision. A survey of the use of blood in the UK indicates that 20% or more of transfusions are inappropriate and that many patients could benefit from safer alternatives [376]. However, in emergency situations the inability to obtain a consent must not prevent or delay the need for essential urgent lifesaving transfusion. The only exception is patients that have a valid Advance Decision Document declining transfusion. Most Jehovah’s witnesses carry a written advance directive declaring their religious convictions not to take a blood transfusion [377]. The blood refusal card directs that no blood is to be given to the owner under any circumstance, even if physicians believe transfusion will be lifesaving [378]. The right of such patients not to be transfused should be respected [379]. However, in the emergency, in the absence of blood refusal card or if there is a reasonable doubt about the validity of a treatment refusal, the physician has a duty of care to take decision that they believe is in the best interest of the patients and render life-saving treatment [380]. The issue of informed consent to have a transfusion is critical because transfused patients potentially lose their ability to be blood donors. In many developed countries, transfusion dependent patients are offered a modified form of consent that requires them to go through an annual review and re-consent [381].

5.7 Prescribing and request for transfusion

The process of prescribing blood components is not necessarily legally restricted to registered medical practitioners. From a safety and efficiency and saving lives point of view, there are clear advantages in allowing non-medical practitioners to authorize transfusion in certain situations. Evidence-based best practice recommends that appropriately trained and competent practitioners including registered nurses and midwives can make clinical decisions and provide written instruction for blood component transfusion. This practice has the potential to deliver a more patient-centred quality service [382, 383]. It is vital that all transfusion prescriptions or written authorization to transfuse a patient blood must be permanent part of a patient clinical records and should contain vital information including patient’s minimum identifiers, information on the blood component to be transfused, the dose, volume rate and any special requirements [384].

5.8 Pre transfusion sampling

Wrong blood in tube’ (WBIT) errors and misidentification at blood sampling, where the blood in the tube is not that of the patient identified on the label is a major cause of ABO incompatible transfusion and fatal haemolytic transfusion reactions. The consequence of these errors can be catastrophic [385]. This type of error is difficult to identify particularly when there is no historic blood group documented in the patients records on the LIMS [386]. Sub optimally labelled samples carry a significantly increased risk of containing blood from the wrong patient. There are several steps that can potentially reduce the risk of this kind of errors; use of electronic systems, ensuring that phlebotomist responsible for sample collection are adequately trained and competent tested; patients must be positively identified and their details (name, date of birth and hospital number) on the sample, dated, timed, and must match those on the request form and patient wrist band [386]. It is generally expected that all inpatients must wear an identity band and the collection and labelling of the sample tubes must be performed at the patient bedside as one uninterrupted process involving one trained and competent staff and one patient. Other requirements include; sample tubes must not be pre-labelled prior to sample collection; sample tubes must be hand labelled legibly; addressograph or printed labels must not be used on the transfusion sample and the transfusion laboratory must maintain a zero-tolerance policy for rejecting samples that do not meet the above minimum requirements [387, 388, 389]. It is also evidence-based best practice to implement a two- specimen rule to allow for the verification of ABO/Rh for blood transfusion [390, 391]. This implementation of two concordant ABO typing results has the potential to detect wrong blood in the tube and prevent the risk of haemolytic transfusion reaction resulting from the transfusion of ABO incompatible blood particularly when there is a discrepancy in the blood group obtained from both sample [392]. Many countries in the West African sub region do not seem to have a LIMS nor a bar-code-based identification. The 2-sample rule is also not being implemented and documentation tends to be hardcopy and paper-based [393]. Countries in the sub region will need to start implementing these best practices to the latter to enhance the safety of blood transfusion service delivery and to reduce the risk of incompatible blood transfusion.

5.9 Collection of blood and delivery in the clinical area

Errors during blood collection of blood from the blood bank have been reported as predominant root cause of wrong blood transfusion and associated haemolytic transfusion reaction [393]. All staff responsible for collecting blood from the blood bank or satellite refrigerators must be trained and competency tested. There is increasing advocacy for the replacement of the predominant manual documentation of blood collection using a transfusion register which is predominant in many settings in the West Africa sub region to the less error- prone electronic blood-tracking systems [394]. This manual documentation system in operation in most settings in the sub region is risky particularly because people bear similar names thus increasing the risk of potentially taking blood meant for a different patient [395]. Electronic blood-tracking systems has a number of advantages over the traditional hardcopy register system; improved quality of transfusion service delivery by reducing transfusion errors; it allows for timely collection and delivery to clinical area, enhances the productivity of nursing staff as well as reduced blood wastage, prevent the risk of taking blood for a wrong patient and unallocated or de-reserved units, provides audit trail as only staff who have been trained and competency tested are given barcode and password to identify themselves on the system. Staff collecting blood is expected to scan the patient barcode containing the minimum patient identifiers which must be checked against the details on the transfusion laboratory-generated crossmatch label attached to the blood pack. Normally if there is no blood allocated for the patient in the fridge the staff will be denied access to the fridge. The system only ensures that only blood that is within its expiry time and date and meant for the desired patient is released for collection. Other advantages of the computer-controlled, electronically- linked information management system is that; minimize the risk of transfusing units that have been out of temperature-controlled storage for too long (>30 minutes); provides a full audit trail of all activity and frees up nursing resources allowing them concentrate on other core nursing duties, prevents the transfusion of incorrectly stored units and out of date product or quarantined; facilitate inventory control management, delivery, tracking and documentation as well as audit trails. Access to electronic databases have greatly facilitated product traceability and biovigilance efforts and it can be linked to LIMS and other IT systems, providing robust documentation and data relevant to transfusion at all stages of the transfusion process (blood sample collection, laboratory testing, blood unit collection from the blood bank and transfusion of blood to the patient, ensuring full documentation and audit trail at every stage [396]. Electronic blood-tracking systems ensure that the right patient receives the right blood component at the right time [397].

6. Receiving blood in the clinical area and safe administration of blood

Transfusion of wrong blood or blood component is the most important error associated with serious morbidity or mortality. Provision of training and competency for healthcare workers involved in blood transfusion, developing standard safety guidelines, raising of hazards and implementation of appropriate preventative measures are critical during all steps of blood and blood component transfusion [397]. There are evidence-based practices that clinical staff involved in blood transfusion will have to implement to prevent transfusion errors. Before attempting to collect blood from the blood bank they must ensure that patient is wearing an identity band, has given consent for transfusion, the transfusion ‘prescription’ has been completed, there is venous access and staff are available to start the transfusion promptly and monitor it correctly. Also except in case of major haemorrhage requiring rapid transfusion of large quantities, only one unit should be collected at a time. Also, transfusion of not urgent blood at night should be avoided. Effective identity checks between patient and the blood unit including the component special requirements are key requirements as it constitutes the final opportunity to avoid potentially fatal mis transfusion (last chance/bus stop to prevent mis transfusion). The check must be performed by two clinical staff for every unit transfused. The unit must be inspected thoroughly for signs of leakage, discoloration or clumps. The prescription and other relevant paperwork should be signed by the person administering the component including the component donation number, date, time of starting and stopping the transfusion, dose/volume of component transfused, and name of the administering practitioner should be recorded in the clinical record. Correct patient identification is crucial in transfusion safety. Failure in patient identification can result in wrong blood typing or transfusion of the wrong blood component. Many of these kinds of incidents are preventable by carefully checking patient data at the bedside prior to commencing the transfusion [398]. Changes in vital signs are regularly seen during transfusion. There is need for clinical staff to be aware of common transfusion reaction signs and symptoms to enable them to differentiate between a normal patient response from a life-threatening reaction [399, 400].

6.1 Monitoring during a blood transfusion

Blood transfusion is associated with adverse reactions or events. Patients having a blood transfusion should be regularly monitored before, during and post transfusion. Patients must be encouraged to report new symptoms. By monitoring and recording vital signs such as temperature, pulse, respiratory rate, and blood pressure regularly we can tell if a patient is having a transfusion reaction. These parameters are determined at baseline (at least 60 minutes) before commencement of the transfusion, 15 minutes after the start and regularly during and after the transfusion. Patient monitoring during transfusion is of paramount importance for prompt detection of transfusion reactions [401]. Transfusion reaction associated with transfusion of ABO incompatibility or bacterial transmission present early after commencing the transfusion [402]. Sometimes patients can have delayed transfusion reaction that will become evident 24 hours post transfusion. It is vital that the transfusion recipient is monitored over the next 24 hours. Any reaction observed during and after the transfusion of a blood component must be reported promptly and investigated. The guidelines of the British Committee for Standards in Haematology recommends that when any of the associated signs and symptoms of transfusion reactions occur, the initial treatment should be based on signs and symptoms rather than on classification [403].

6.2 Enhancing blood transfusion safety across the West African sub-region

Safe blood is a crucial component in improving health care and in preventing the transmission of infections. The two major challenges associated with blood transfusion service delivery across the West African sub region is that adequacy and safety [2, 404]. Developing countries have continued to lag behind in contributing her own quota to the allogenic blood pool globally. Out of the 92 million blood units were donated worldwide in 2008, only an insignificant 4 million (4.3%) were donated in sub-Saharan Africa- a continent that is home to approximately 12% of the global population [405]. The rate of blood donation across the region has remained consistently lower than rates in developed economies (4–5 per 1000 compared to 30 donations per 1000) respectively [406]. The World Health Organization recommends blood transfusion from low risk and altruistic regular voluntary non-remunerated blood donors (VNRBDs). However, VNRBDs represent <50% of whole blood donations in low-income countries compared with 76–100% in developed economies. The sub-region will need to abolish the unsafe commercial remunerated blood donation. Efforts should be made to enlighten the sub-region that family replacement donors are unsafe, there is difficulty in replacing blood in quantity and type through family replacement donation and blood donated can put transfusion recipient who are females of childbearing age at risk of developing alloantibodies that can cause HTR and HDFN if they receive blood from their husbands and his relatives. The region will need to look for innovative ways to encourage community members to change their mentality from being family replacement donors to becoming voluntary non-remunerated donors. VNRBDs are key to the maintenance of a safe and adequate blood supply. Education and public enlightenment, innovation, and pragmatic approach in the aspect of recruitment, retention, non-cash motivation and renewal of an active volunteer and non-remunerated donor pool from the massive young population in the sub region is key to safe and sustainable blood transfusion service delivery [407]. Transfusion-transmissible infections, such as HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, and malaria are prevalent across the sub region and have remained a source of safety concern for transfusion recipients. Transfusion of sub- optimally screened blood is the cause of 5–10% of HIV infections in sub-Saharan Africa and about 12.5% of transfusion recipients in the region are at risk of post-transfusion hepatitis [408]. Unsafe blood transfusion has a significant effect (socio, economic and health) on the sub region, families, communities, and the wider society [409]. The various markers of infection for these infective agents appear at different times after infection. The window periods (period between infection and availability of screening marker in the blood of the donor) vary depending on the infective agent (range from few days to months), the infectious agent and the screening marker and the technology used. In the window period a screening marker may not be detectable in a recently infected donor even though the donor may be infectious. Nucleic acid (RNA/DNA of the infectious agent) is the first detectable target to appear in blood, followed by the antigen (produced by the infectious agent), and finally the antibody following an immune response in the donor. The sub region will need to implement a policy of universal/mandatory screening of blood donors for HIV-1 and HIV-2, Hepatitis B, Hepatitis C and Syphilis as a minimum requirement [410]. The infectious agent, the screening marker, and the minimum technology to be employed should be defined by way of policy. For HIV-1 and HIV-2 screening using a combination of HIV antigen-antibody or HIV antibodies as a minimum and where possible nucleic acid testing is advocated. Screening for hepatitis B using hepatitis B surface antigen (HBsAg). Hepatitis C screening for either a combination of HCV antigen-antibody or HCV antibodies and where possible nucleic acid testing while for syphilis (Treponema pallidum) screening for specific treponemal antibodies should be implemented across the sub region. The use of only antibody-based test for screening donors for HIV and HCV should be discouraged to prevent the risk of introducing donor blood in the window phase of infection into the blood donor pool [411]. All efforts and energy need to be invested by member countries of ECOWAS to minimize the risks of transfusion-transmitted infection particularly during the window phase of infectious agent to make blood safer [2]. Implementation of stringent donor selection criteria and deferral system is the first step in determining the suitability of a potential blood donor to donate blood [412]. It can determine eligibility and identify donors whose behaviours put them potentially at risk for blood donation warranting either temporal or permanent deferral. The implementation of a robust donor deferral strategy can have a positive impact on transfusion safety in the West African sub-region [413]. A better understanding of the reasons for deferral of potential blood donors across the sub region could assist in donor recruitment planning and gives insight into the general health of the population in terms of prevalence of TTIs and anaemia. The presence of anaemia and risk of TTIs are the predominant contributors to donor deferral among donors [414, 415]. Member countries in the sub region will need to improve on the donor screening and deferral procedures as well as serologic testing. The aim of deferral is to facilitate the exclusion of donors from potentially higher risk populations to enhance patient safety [416]. The sub region will need to develop an efficient donor screening and deferral system to ensure the safety of both prospective donors and recipients [417]. The need for allogenic blood in the West African sub region has continued to be on the increase for several reasons; increase in the number of elective surgeries, failure to match demand and supply, suboptimal functioning of the national blood transfusion services, lack of relevant policies, trained personnel, funding and appropriate infrastructure in member states, dominance of unsafe family replacement and commercial remunerated blood transfusion rather than safe and altruistic voluntary non-remunerated blood donors, old and emerging threats of transfusion-transmitted infection, poor management of coagulopathy, major haemorrhage and bleeding disposition in surgical patients and pregnant women, prevalent insurgencies and communal clashes, increase in road traffic accidents due to poor road infrastructure in some member states, armed conflicts, insurgency and banditry, high prevalence of sickle cell disease, nutritional and malaria associated anaemia and pregnancy-related complications. All these factors have made allogenic blood a vital but limited commodity across the sub region. The region will need to think strategically out of the box to identify innovative ways to recruit and retain voluntary low-risk blood donors. Education, public enlightenment, and collaboration with stakeholders are key to changing the erroneous belief of the people towards donation of blood [418]. Countries in the West African sub region need to be smart, flexible and do things differently to ensure the adequacy and safety of blood transfusion service delivery in the sub region. Efforts should be made to make transfusion safer by implementing best practices in donor selection and screening. The use of other alternatives to allogenic blood (autologous transfusion, use of pharmacologic agents like oral, IV iron and erythropoietin to optimize haemoglobin of patients particularly those going for elective surgery, optimal management of trauma and associated major haemorrhage (trauma, surgical, ante and post-partum) by using haemorrhage limiting medication like antifibrinolytic, prothrombin complex concentrate, Novo7 and vitamin K [419]. The implementation of component therapy and universal leucodepletion of blood products will go a long way in ensuring the optimal management and safety of our limited allogenic blood stock. The need for the National blood transfusion services across the sub region to work synergistically under the umbrella of ECOWAS cannot be over emphasized to drive the organization and management, blood donor recruitment, collection, testing of donor blood and appropriate clinical use of blood. The sub region will need to invest significantly on human and infrastructural capital development by increasing the budget for training aimed at an increasing the number of transfusions service-related skilled workforce, providing an enabling working environment and proper renumeration of health workers. These implementations have the potential to improve the access to adequate and safe blood transfusion across the sub region.

7. Conclusion and recommendations

Blood transfusion service delivery across the west African sub region faces daunting but surmountable challenges bordering around adequacy and safety. The challenge of providing adequate and safe blood and blood product across the sub region is multi-dimensional and include; lack of transfusion policies and a fit for purpose National blood transfusion service in some ECOWAS countries, reliance on unsafe family replacement and commercial remunerated donors rather than safe benevolent voluntary non-remunerated donors who donate blood for altruistic purpose, suboptimal funding required to fund a quality blood transfusion service, inadequate number of skilled manpower, lack of political will to implement the haemovigilance system, reliance on suboptimal antibody-based screening method for donor screening for HIV, transfusion of leucocyte rich whole blood rather than leuco-depleted component therapy, suboptimal pre-transfusion screening of patients that require a red cell transfusion, poor cold chain management of blood and blood products, absence of specialized blood products like gamma irradiated blood CMV negative and antigen negative blood etc. required by certain patients group, poor management of Rh negative pregnancy and absence of universal access to anti-D prophylaxis, absence of a quality management system-based blood transfusion service, absence of indication coding tool to facilitate the effective clinical use of blood, lack of alloantibody prevention measures, poor management of haemolytic disease of the foetus and newborn, suboptimal use of laboratory testing to determine the coagulopathic status of patients billed for surgery to facilitate the effective management of the coagulopathy prior to surgery to reduce the risk of haemorrhage, poor management of major haemorrhage, suboptimal use of pharmacologic and non-pharmacologic alternatives to allogenic blood in anaemic and bleeding patients. These factors affect the adequacy and safety of blood transfusion across the sub-region.

8. Recommendations

We recommend the implementation of the following evidence-based best practices to ensure the safety, adequacy and timely provision of blood and blood products across the West African sub-region.

1. Countries in the sub region should implement a blood component to facilitate the optimum utilization of donated blood.

2. Implementation of a policy on universal leucodepletion of blood products transfused across the sub region to prevent the challenges associated with the transfusion of leucocyte- rich blood products.

3. There is need for government across the sub region to invest significantly in funding the national blood transfusion services to facilitate the safety and adequacy of blood transfusion.

4. Governments across the ECOWAS region need to invest in critical infrastructure including the utilization of the readily available green solar energy resource to manage the cold chain management of blood and blood products.

5. There should be the implementation of evidence-based best practices in alloimmunization prevention to prevent the incidence of haemolytic disease of the foetus and newborn across the sub-region.

6. Implementation of best practices in pre-transfusion testing including alloantibody screening and panel testing for patients whose alloantibody screening is positive to facilitate the provision of antigen negative donor blood for transfusion to the recipient.

7. There is need for a paradigm shift from the use of the less sensitive conventional tube method to the more sensitive column agglutination technique for blood transfusion testing including blood group, alloantibody testing and crossmatching.

8. There is need to develop a major haemorrhage protocol for use across the region to facilitate the effective management of patients with major haemorrhage.

9. Implementation of a donor screening algorithm for use across the sub region that reduces the risk of introducing donor blood in the window phase of transfusion -transmissible viral infection into the subregional blood pool.

10. There is need to develop a sub-regional protocol for the management of transfusion dependent patients to implement best practices like the implementation of extended phenotyping and universal access to use of chelating agents in these patients.

11. Implementation of a sub-regional indication coding tool to facilitate the effective clinical use of blood and blood products.

12. Provision of specialized products that is clinically indicated in several patients’ groups like gamma irradiated blood, CMV negative blood, antigen negative blood, etc.

13. Implementation of a quality management-oriented blood transfusion service across the sub region that facilitates the delivery of a continually improving quality transfusion service.

14. There is need for the optimum remuneration, motivation and retention of healthcare workers involved in the entire blood transfusion process to prevent the brain drain of the sub-region human resource assets.

15. There is need for countries across the sub region to provide adequate budgetary allocation for the running of National Blood Transfusion services to facilitate the adequacy and safety of blood transfusion service delivery.

16. The is need for implementation of best practices, in patient identification, informed consent, prescription, pre- transfusion sampling, collection of blood from storage area, receipt of blood in clinical area, administration and monitoring during blood of transfusion.

17. There is need for the implementation of a sub-regional policy that promote the use of pharmacologic and non-pharmacologic alternatives in anaemic and bleeding patients to facilitate the optimum utilization of our limited allogenic blood stock on patients in whom these alternatives are contraindicated.

18. The implementation of a policy on universal access to anti-D prophylaxis in non-previously sensitized pregnant Rhesus D negative women as well as the introduction of cell-free foetal DNA testing for all Rh D negative pregnant women across the sub region to identify those carrying Rh D negative foetuses for which the use of the prophylaxis can be spared.

19. Facilities for non-invasive foetal maternal haemorrhage testing (Kleihauer or flow cytometry) should be provided to facilitate the optimum management of Rhesus D negative non-previously sensitized pregnant women following a potential sensitizing event to facilitate the administration of optimum dose of anti-D prophylaxis to prevent the women from being sensitized.

20. There is urgent need for the implementation of a unified haemovigilance system across the sub region that facilitates the reporting of all near misses, adverse events and reaction associated with donation and transfusion of blood allowing for the provision of a continually improving transfusion service delivery across the sub region.

21. There is need for the implementation of a policy that promotes safe and altruistic voluntary non- remunerated donor run national blood transfusion service rather than the unsafe family replacement donor system.

22. There should be a sub-regional policy to outlaw unsafe commercial remunerated donation of blood.