Open Access is an initiative that aims to make scientific research freely available to all. To date our community has made over 100 million downloads. It’s based on principles of collaboration, unobstructed discovery, and, most importantly, scientific progression. As PhD students, we found it difficult to access the research we needed, so we decided to create a new Open Access publisher that levels the playing field for scientists across the world. How? By making research easy to access, and puts the academic needs of the researchers before the business interests of publishers.
We are a community of more than 103,000 authors and editors from 3,291 institutions spanning 160 countries, including Nobel Prize winners and some of the world’s most-cited researchers. Publishing on IntechOpen allows authors to earn citations and find new collaborators, meaning more people see your work not only from your own field of study, but from other related fields too.
To purchase hard copies of this book, please contact the representative in India:
CBS Publishers & Distributors Pvt. Ltd.
www.cbspd.com
|
customercare@cbspd.com
Coagulopathy is of intense interest in the fields of emergency medicine, with many recent studies of coagulation biomarkers for clinical use. The occurrence of disseminated intravascular coagulation (DIC) also resulted in the activation of studies about the coagulopathy. At present DIC has been admitted in many clinical conditions and many coagulation biomarkers have been studied. Fibrin degradation product (FDP) and D-dimer are one type of coagulation biomarker. A characteristic of FDP and D-dimer is the rapid and dynamic elevation of their levels when fibrinolysis occurs in several acute diseases. In this chapter, we present the clinical application of FDP and D-dimer. In trauma, FDP and -dimer have been used for the evaluation of trauma severity, to predict the likelihood of hemorrhage and to evaluate the need for the transfusion of packed red blood cells. In cardiac pulmonary arrest (CPA), FDP and D-dimer have been useful for predicting the return of spontaneous circulation. Thus, the measurement of coagulation biomarkers is useful in the diagnosis and/or treatment of trauma and CPA.
Department of Emergency Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
Shuichi Hagiwara
Department of Emergency Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
Kiyohiro Oshima
Department of Emergency Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
*Address all correspondence to: aokimakoto@gunma-u.ac.jp
1. Introduction
Fine balance exists between coagulation and fibrinolysis within the coagulation system, with coagulopathy defined as the failure of this balance. Coagulopathy has long been known to occur in several acute diseases such as cardiovascular disease [1], infection [2] and trauma [3]. In response, coagulation biomarkers have been identified and used in clinical practice in recent years to diagnose and treat several diseases of the coagulation system.
There is a variety of coagulation biomarkers used in real clinical situation. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen has been used to test the coagulation function from long ago in hematologic disorder, liver disease, disseminated intravascular coagulation (DIC) and to monitor the use of anticoagulation drugs. Owing to the recent progress in measuring method, the more minute coagulation biomarkers can be measured and divided into coagulation systems and fibrinolytic systems. Each example is thrombin-antithrombin complex (TAT), soluble fibrin (SF) and soluble fibrin monomer complex (SFMC) in coagulation systems, and Fibrin degradation product (FDP) and D-dimer in fibrinolytic systems. They are relatively new coagulation biomarkers and the characteristics of them are to be rapidly elevated in acute phase. In clinical situation, they are practically used to detect the venous thromboembolism [4, 5, 6]. Besides, FDP and D-dimer are more studied, and the clinical applications of these coagulation biomarkers are ranging from diagnosing [7] to the treatment [8].
In this chapter, we present information on the successful use of FDP, D-dimer and fibrinogen in clinical practice. Finally, we demonstrate the prospects of the clinical application of coagulation biomarkers.
2. Disseminated intravascular coagulation (DIC) and clinical use of coagulation biomarkers
The occurrence of DIC has been the definitive trigger for the use of coagulation biomarkers in the diagnosis of this disease. DIC is characterized by the widespread activation of coagulation, which results in the intravascular formation of fibrin and, ultimately, the thrombotic occlusion of small- and mid-sized vessels [9, 10, 11]. Intravascular coagulation can also compromise the blood supply to organs and peripheral cells, and, in conjunction with hemodynamic and metabolic derangements, may contribute to the failure of multiple organs [12].
DIC is present in many clinical conditions (Table 1) [12].
Sepsis Trauma Serious tissue injury Head injury Fat embolism Cancer Myeloproliferative diseases Solid tumors (e.g., pancreatic carcinoma, prostatic carcinoma) Obstetrical complications Amniotic-fluid embolism Abruption placentae Vascular disorders Giant hemangioma (Kasabach-Merritt syndrome) Aortic aneurysm Severe hepatic failure Reactions to toxins (e.g., snake venom, drugs and amphetamines) Immunologic disorders Severe allergic reaction Hemolytic transfusion reaction Transplant rejection
Table 1.
Common clinical conditions associated with disseminated intravascular coagulation.
Of these clinical conditions, coagulation biomarkers have been especially used in the treatment of sepsis. The clinical criteria for the early diagnosis of DIC have incorporated the use of several coagulation biomarkers such as FDP, D-dimer, PT, and fibrinogen [13, 14, 15, 16]. In addition, the two endogenous anticoagulants, antithrombin and protein C, are found decreased in patients with DIC, and are useful in predicting the outcome of such patients, as well as those with sepsis [17, 18]. Furthermore, thrombomodulin, tissue factor pathway inhibitor, Von Willebrand factor and Adamts 13 are also useful in clinical situations [19, 20].
Of these coagulation biomarkers, we focused on the use of FDP and D-dimer in several clinical conditions. D-dimer is a specific protein fiber degradation product of cross-linked fibrin in response to hydrolysis by fibrinolytic enzymes [21, 22]. When the thrombus degrades, D-dimer may be released into the circulatory system [23]. In normal blood, the level of D-dimer is low, but once thrombosis occurs, the D-dimer level rises [24]. FDP is the degradation product of fibrous protein. In normal blood, the level of FDP is also low; however, the FDP level also increases when fibrinolysis occurs. FDP is a mitogen for many cell types, promoting the proliferation of endothelial cells, smooth muscle cells, and fibroblasts, as well as cholesterol deposition [25]. FDP can also induce the adhesion and accumulation of white blood cells, which results in damage to the blood vessel endothelium [26].
In our facility, FDP and D-dimer are measured by an immunoturbidimetric method using Cs-2000i and Cs-5100 systems (Sysmex Corporation., Hyogo, Japan; Figure 1). It takes about 15–20 minutes to measure FDP and D-dimer with this instrument.
Figure 1.
Cs-5100 systems to measure FDP and D-dimer (Sysmex Corporation., Hyogo, Japan).
DIC has been well known to occur in trauma since the 1960s, especially in relation to head trauma (Table 1). Coagulopathy in trauma was believed to originate as a consequence of fluid administration and hypothermia [27]. However, in the 2000s, the concept of acute traumatic coagulopathy (ATC) first appeared [27] with the demonstration that an organ and/or cell injury itself caused the coagulopathy. Using coagulation biomarkers such as PT, APTT and thrombin time (TT), acute traumatic coagulopathy was shown to be associated with mortality and severe trauma.
Initially, the concept of ATC was reported mainly in severe trauma, because PT, APTT and TT were found to have normal values in lightly and mildly traumatized patients. However, using fibrinolytic coagulation biomarkers such as FDP and D-dimer, we also detected ATC in lightly and mildly traumatized patients. This has been described in our first report on the clinical usefulness of coagulation biomarkers [28].
3.1. The relationship between coagulation biomarkers and trauma severity
Our study reported that of all coagulation biomarkers, FDP and D-dimer were associated with the severity of trauma [28]. We have previously demonstrated an association between FDP and D-dimer, and a trauma score such as the Injury Severity Score (ISS) [29]. The ISS has been one of the most common and useful scoring systems to evaluate the severity of trauma and is used widely throughout the world. In clinical practice, the ISS is calculated for each anatomical injury according to the results of physical examinations, surgery and imaging studies; therefore, the ISS cannot be calculated in an initial emergency field. However, we can predict ISS using FDP and D-dimer.
In this study, the area under receiver operating characteristics curves (AUROCs) of FDP and D-dimer for predicting an ISS ≥ 9 were 0.757 and 0.756, and the sensitivity and specificity of FDP and D-dimer based on the Youden’s index were 75.9 and 68.4%, and 75.9 and 73.7%, respectively. This demonstrated that we could predict mild to severe injury (ISS ≥ 9) with about 70% sensitivity and specificity; this finding signaled to trauma physicians and surgeons that minor injury was not to be overlooked. Because several minor injuries, such as minute spinal column and rib fractures, are sometimes hard to detect, FDP and D-dimer can be used as supplementary diagnostic tools.
In addition, we have adopted this finding to more severe trauma. In the previous study, we investigated the association between FDP and D-dimer, and an ISS ≥ 9. In a similar setting, we calculated the AUROCs of FDP and D-dimer for predicting ISS ≥ 9, ISS ≥ 16 and ISS ≥ 25 (Figure 2).
Figure 2.
(a) Receiver operating characteristic (ROC) curve of coagulation biomarkers to predict the injury severity score (ISS) of a patient with trauma ≥9 points. FDP, fibrin degradation products. (b) Receiver operating characteristic (ROC) curve of coagulation biomarkers to predict the injury severity score (ISS) of a patient with trauma ≥16 points. FDP, fibrin degradation products. (c) Receiver operating characteristic (ROC) curve of coagulation biomarkers to predict the injury severity score (ISS) of a patient with trauma ≥25 points. FDP, fibrin degradation products.
These figures demonstrated that the predictivity of FDP and D-dimer for ISS was more accurate, especially in severe trauma. In Table 2, the AUROC and cut-off points of FDP and D-dimer to predict whether the ISS was over the 25 were the highest at 0.818 and 0.813, respectively. The sensitivities and specificities, based on the Youden’s index, of FDP and D-dimer to predict an ISS over 25 were 73.3 and 82.7%, and 76.7 and 78.4%, respectively. These findings are novel because they are based on a patient’s trauma severity, allowing the development of definitive treatment more rapidly.
FDP D-dimer
ISS ≥ 9
ISS ≥ 16
ISS ≥ 25
AUROC (95% CI)
0.743 (0.681–0.806) 0.751 (0.689–0.814)
0.691 (0.624–0.759) 0.694 (0.628–0.761)
0.818 (0.735–0.901) 0.813 (0.732–0.894)
Cut-off point
32.1 μg/mL 6.5 μg/mL
32.1 μg/mL 12.8 μg/mL
101.4 μg/mL 28.2 μg/mL
Sensitivity, %
59.4 73.1
67.8 65.6
73.3 76.7
Specificity, %
79.8 66.7
64.9 66.1
82.7 78.4
Table 2.
Area under the receiver operating characteristic curve and cut-off points of FDP and D-dimer to predict whether the ISS is over 9, 16 or 25.
CI, confidence interval; FDP, fibrin degradation product; AUROC, area under the receiver operating characteristic curve; ISS, injury severity score.
3.2. The prediction of extravasation in pelvic fracture using coagulation biomarkers
In the section of the relationship between coagulation biomarkers and trauma severity the ability of FDP and D-dimer to predict trauma severity was demonstrated. Therefore, we also applied this to pelvic fracture [30]. Pelvic fracture is an independent risk factor for death after blunt trauma. It is associated with increased mortality in blunt trauma, with rates up to 30% [31, 32, 33]. In pelvic fracture, retroperitoneal hemorrhage may induce hemodynamic instability, with 5–20% originating from arterial bleeding [34].
In a clinical situation, the standard tool to detect arterial bleeding in a pelvic fracture has been computed tomography (CT) using contrast material; however, several problems exist with CT scanning. One problem is the specificity of CT scanning to detect arterial bleeding in pelvic fracture [35] is decreased. Another problem is that the quality of the CT scanning may be related to the scanning protocol and can be affected by interference caused by vasospasm, consequently affecting the diagnostic ability of physicians [36, 37]. Thus, we evaluated the predictive ability of coagulation biomarkers to detect arterial bleeding and whether these could be used as alternative tools for CT scanning.
Our report highlighted the highly accurate ability of FDP and D-dimer to detect arterial bleeding in a pelvic fracture; the AUROCs of FDP and D-dimer were 0.900 and 0.882, respectively (Table 3) [30]. In addition, in this study we calculated the ratios of FDP to fibrinogen, and of D-dimer to fibrinogen. Fibrinogen is said to be an independent risk factor of mortality and severity in blunt trauma patients [38, 39, 40], and a predictor of transfusion [41, 42]. We combined the high FDP and D-dimer, and the low fibrinogen, to the ratio of FDP to fibrinogen and the ratio of D-dimer to fibrinogen, this was a novel finding. This ratio was subsequently developed to the next stage [43, 44].
FDP
D-dimer
Ratio of FDP to fibrinogen
Ratio of D-dimer to fibrinogen
Hemoglobin level
Lactate level
AUROC (95% CI)
0.900 (0.765–1.000)
0.882 (0.728–1.000)
0.918 (0.797–1.000)
0.900 (0.773–1.000)
0.815 (0.656–0.974)
0.765 (0.563–0.967)
Cut-off point
126.8 μg/mL
46.0 μg/mL
0.656
0.215
11.0 g/dL
2.75 mmol/L
Sensitivity, %
94.1
94.1
94.1
94.1
61.1
58.8
Specificity, %
90.0
90.0
90.0
80.0
0.0
85.7
Table 3.
Area under the receiver operating characteristic curves and cut-off points of parameters to predict arterial extravasation in pelvic fracture patients.
CI, confidence interval; FDP, fibrin degradation product; AUROC, area under the receiver operating characteristic curve.
3.3. Prediction of the need for packed red blood cell transfusions using coagulation biomarkers
We applied coagulation biomarkers to the prediction of the need for packed red blood cell transfusions [43]. For a long time, many investigators have discussed how to predict massive transfusion requirements in blunt trauma patients [45, 46, 47, 48, 49, 50, 51]. The characteristics of FDP and D-dimer were correlated with the trauma severity: from relatively light to severe trauma [28]. This feature has been utilized to predict not only patients requiring massive transfusions, but also whether patients needed packed red blood cells or not. Coagulation biomarkers, especially, the ratio of FDP to fibrinogen, were found to be the most accurate markers for predicting the need for packed red blood cell transfusions (Table 4) [43].
AUROC (95% CI)
Cut-off point
Sensitivity (%)
Specificity (%)
ABC
0.591 (0.420–0.763)
0.5
21.4
96.7
GCS
0.716 (0.547–0.885)
12.5
96.4
42.9
Ht
0.667 (0.503–0.830)
31.3%
97.3
35.7
PT–INR
0.859 (0.760–0.958)
1.065
71.4
90.1
APTT
0.684 (0.501–0.866)
36.45 s
42.9
96.4
Fib
0.877 (0.808–0.947)
245.5 mg/dL
64.3
100
FDP
0.874 (0.784–0.963)
45.65 μg/dL
78.6
80.4
FDP/Fib ratio
0.899 (0.819–0.979)
0.202 × 10−3
85.7
82.3
Table 4.
Results of receiver operating characteristic curves analysis.
AUROC, area under the receiver operating characteristic curve; CI, confidence interval; ABC, assessment of blood consumption score; GCS, Glasgow Coma Scale; Ht, hematocrit; PT-INR, international normalized ratio of prothrombin time; APTT, activated partial thromboplastin time; Fib, fibrinogen; FDP, fibrin degradation product.
In recent decades, the science of cardiac pulmonary arrest (CPA) has been improving due to the widespread adoption of guidelines by the International Liaison Committee on Resuscitation (ILCOR). The 2015 guidelines by the Japan Resuscitation Council, which is one of the subsidiary organizations of ILCOR, enumerates predictive candidates for outcomes of patients with an out-of-hospital cardiac arrest (OHCA), such as S-100B, neuron specific enolase, imaging findings, brain waves, among others. However, it is presently difficult to predict favorable neurological outcomes or the survival of patients with OHCA [52]. Recently, several reports have suggested that blood coagulation makers reflected the prognosis of patients with CPA. The occurrence of fibrinolysis in patients with CPA has been noticed for a long time [53]; however, coagulation biomarkers has not been clinically applied to CPA until recently, with clinical applications with regard to CPA having appeared since the 2010s. For example, FDP and D-dimer are associated with the return of spontaneous circulation (ROSC) and have been useful for predicting ROSC [54] (Table 5) [54]. Other reports have demonstrated that a high D-dimer concentration on admission predicts a poorer outcome [55], and that the FDP level predicts neurological outcomes [56].
AG
ACAG
FDP
D-dimer
AUROC (95% CI)
0.664 (0.514–0.815)
0.667 (0.516–0.818)
0.714 (0.571–0.858)
0.707 (0.561–0.853)
Cut-off point
27.8 mmol/L
31.7 mmol/L
29.4 μg/mL
10.2 μg/mL
Sensitivity, %
84.4
78.1
87.5
87.5
Specificity, %
45.0
55.0
50.0
55.0
Table 5.
Areas under receiver operating characteristic curves and cut-off points of parameters that predict whether a patient with cardiopulmonary arrest can achieve a return of spontaneous circulation after effective cardiopulmonary resuscitation.
Coagulation disorders are associated with several diseases and symptoms in emergency medical fields. The occurrence of DIC is a modern topic and has been accelerating the studies about the coagulation biomarkers. We demonstrated that testing for and measuring FDP and/or DD may be advantageous in diagnosing and/or treatment of trauma and CPA.
I would like to thank the Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine for measuring the coagulation biomarkers.
The authors declare that they have no competing interests.
References
1.Scott J, Humphreys DR. Dissecting aortic aneurysm and disseminated intravascular coagulation. British Medical Journal. 1977;1:24
2.Corrigan Jr JJ, Ray WL, May N. Changes in the blood coagulation system associated with septicemia. The New England Journal of Medicine. 1968;279:851-856. DOI: 10.1056/NEJM196810172791603
3.Salzman EW. Does intravascular coagulation occur in hemorrhagic shock in man? The Journal of Trauma. 1968;8:867-871
4.Lee SY, Niikura T, Iwakura T, Sakai Y, Kuroda T, Kurosaka M. Thrombin-antithrombin III complex tests. Journal of Orthopaedic Surgery (Hong Kong). 2017;25:170840616684501
5.Mitani G, Takagaki T, Hamahashi K, Serigano K, Nakamura Y, Sato M, Mochida J. Associations between venous thromboembolism onset, D-dimer, and soluble fibrin monomer complex after total knee arthroplasty. Journal of Orthopaedic Surgery and Research. 2015;10:172
6.Wells PS, Ihaddadene R, Reilly A, Forgie MA. Diagnosis of venous Thromboembolism: 20 years of progress. Annals of Internal Medicine. 2018;168:131-140
7.Kotani Y, Toyofuku M, Tamura T, Shimada K, Matsuura Y, Tawa H, Uchikawa M, Higashi S, Fujimoto J, Yagita K, Sato F, Atagi Y, Hamasaki T, Tsujimoto T, Chishiro T. Validation of the diagnostic utility of D-dimer measurement in patients with acute aortic syndrome. European Heart Journal. Acute Cardiovascular Care. 2017;6:223-231
8.Suehiro E, Koizumi H, Fujiyama Y, Yoneda H, Suzuki M. Predictors of deterioration indicating a requirement for surgery in mild to moderate traumatic brain injury. Clinical Neurology and Neurosurgery. 2014;127:97-100
9.Marder VJ, Feinstein DI, Francis CW, Colman RW. Consumptive thrombohemorrhagic disorders. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, editors. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd ed. Philadelphia: J.B. Lippincott; 1994. pp. 1023-1063
10.Bone RC. Modulators of coagulation. A critical appraisal of their role in sepsis. Archives of Internal Medicine. 1992;152:1381-1389. DOI: 10.1001/archinte.1992.00400190023007
11.Müller-Berghaus G, Ten Cate H, Levi M. Disseminated intravascular coagulation. In: Verstraete M, Fuster V, Topol EJ, editors. Cardiovascular Thrombosis: Thrombocardiology and Thromboneurology. 2nd ed. Philadelphia: Lippincott-Raven; 1998. pp. 781-801
12.Levi M, Ten Cate H. Disseminated intravascular coagulation. The New England Journal of Medicine. 1999;341:586-592. DOI: 10.1056/NEJM19908193410807
13.Yasunaga K. Diagnostic criteria of disseminated intravascular coagulation (DIC). Nihon Rinsho. 1975;33:3380-3388 (article in Japanese)
14.Kobayashi N, Maekawa T, Takada M, Takada M, Gonmori H. Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the research committee on DIC in Japan. Bibliotheca Haematologica. 1983;49:265-275
15.Taylor Jr FB, Toh CH, Hoots WK, Wada H, Levi M, Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Throm-bosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thrombosis and Haemostasis. 2001;86:1327-1330
16.Gando S, Iba T, Eguchi Y, Ohtomo Y, Okamoto K, Koseki K, Mayumai T, Murata A, Ikeda T, Ishikura H, Ueyama M, Ogura H, Kushimoto S, Saitoh D, Endo S, Shimazaki S, Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) Study Group. A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: Comparing current criteria. Critical Care Medicine. 2006;34:625-631
17.Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, Marey A, Lestavel P. Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest. 1992;101:816-823. DOI: 10.1378/chest.101.3.816
18.Macias WL, Nelson DR. Severe protein C deficiency predicts early death in severe sepsis. Critical Care Medicine. 2004;32:S223-S228
19.Iba T, Ito T, Maruyama l JB, Brenner T, Muller MC, Juffermans NP, Thacil J. Potential diagnostic markers for disseminated intravascular coagulation of sepsis. Blood Reviews. 2016;30:149-155. DOI: 10.1016/j.blre.2015.10.002
20.Wada H, Thachil J, Di Nisio M, Mathew P, Kurosawa S, Gando S, Kim HK, Nielsen JD, Demfle CE, Levi M, Toh CH. The Scientific Standardization Committee on DIC of the International Society on Thrombosis Haemostasis. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. Journal of Thrombosis and Haemostasis. 2013;11:761-767. DOI: 10.1111/jth.12155
21.Ay C, Vormittag R, Dunkler D, Simanek R, Chiriac AL, Drach J, Quehenberger P, Wagner O, Zielinski C, Pabinger L. D-dimer and prothrombin fragment 1 + 2 predict venous thromboembolism in patients with cancer: Results from the Vienna Cancer and thrombosis study. Journal of Clinical Oncology. 2009;27:4124-4129. DOI: 10.1200/JCO/2008.21.7752
22.Kline JA, Hogg MM, Courtney DM, Miller CD, Jones AE, Smithline HA. D-dimer threshold increase with pretest probability unlikely for pulmonary embolism to decrease unnecessary computerized tomographic pulmonary angiography. Journal of Thrombosis and Haemostasis. 2012;10:572-581. DOI: 10.1111/j.1538-7836.2012.04647.x
23.Suzuki T, Distante A, Zizza A, Trimarchi S, Villani M, Salerno Uriate JA, De Luca Tupputi Schinosa L, Renzulli A, Sabino F, Nowak R, Birkhahn R, Hollander JE, Counselman F, Vijayendran R, Bossone E, Eagle K. IRAD-bio investigators. Diagnosis of acute aortic dissection by D-dimer: The international registry of acute aortic dissection substudy on biomarkers (IRAD-bio) experience. Circulation. 2009;119:2702-2707. DOI: 10.1161/CIRCULATIONAHA.108.833004
24.Raghini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A, Rutschmann OT, Sanchez O, Jaffrelot M, Trinh-Duc A, Le Gall C, Moustafa F, Principe A, Vanhouten AA, Ten Wolde M, Douma RA, Hazelaar G, Erkens PM, Van Kralingen KW, Grootenboers MJ, Durian MF, Cheung YW, Meyer G, Bounameaux H, Huisman MV, Kamphuisen PW, Le Gal G. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: The ADJUST-PE study. Journal of the American Medical Association. 2014;311:1117-1124. DOI: 10.1001/jama.2014.2135
25.Naito M. Effects of fibrinogen, fibrin and their degradation products on the behaviour of vascular smooth muscle cells. Nihon Ronen Igakkai Zasshi. 2000;37:458-463 (in Japanese). DOI: 10.3143/geriatrics.37.458
26.Yakovlev S, Zhang L, Ugarova T, Medved L. Interaction of fibrin(ogen) with leukocyte receptor alpha M beta 2 (Mac-1): Further characterization and identification of a novel binding region within the central domain of the fibrinogen gamma-module. Biochemistry. 2005;44:617-626. DOI: 10.1021/bi048266w
27.Brohi K, Singh J, Heron M, Coats T. Acute traumatic Coagulopathy. The Journal of Trauma. 2003;54:1127-1130. DOI: 10.1097/01.TA.0000069184.82147.06
28.Hagiwara S, Oshima K, Aoki M, Murata M, Ishihara K, Kaneko M, Furukawa K, Ohyama Y, Tamura J. Usefulness of fibrin degradation products and d-dimer levels as biomarkers that reflect the severity of trauma. Journal of Trauma and Acute Care Surgery. 2013;74:1275-1278. DOI: 10.1097/TA.0b013e31828cc967
29.Baker SP, O’Neill B, Haddon Jr W, Long WB. The injury severity score: A method for describing patients with multiple injuries and evaluating emergency care. Journal of Trauma. 1974;14:187-196
30.Aoki M, Hagiwara S, Tokue H, Shibuya K, Kaneko M, Murata M, Nakajima J, Sawada Y, Isshiki Y, Ichikawa Y, Oshima K. Prediction of extravasation in pelvic fracture using coagulation biomarkers. Injury. 2016;47:1702-1706. DOI: 10.1016/j.injury.2016.05.012
31.Schulman JE, O’Toole RV, Castillo RC, Manson T, Sciadini MF, Whitney A, Pollak AN, Nascone JW. Pelvic ring fractures are an independent risk factor for death after blunt trauma. The Journal of Trauma. 2010;68(4):930. DOI: 10.1097/TA.0b013e3181cb49d1
32.Burgess AR, Eastridge BJ, Young JW, Ellison TS, Ellison Jr PS, Poka A, Bathon GH, Brumback RJ. Pelvic ring disruptions: Effective classification system and treatment protocols. The Journal of Trauma. 1990;30:848-856
33.Dalal SA, Burgess AR, Siegel JH, Young JW, Brumback RJ, Poka A, Dunham CM, Gens D, Bathon H. Pelvic fracture in multiple trauma: Classification by mechanism is key to pattern of organ injury, resuscitative requirements, and outcome. The Journal of Trauma. 1989;29:981-1000
34.Dyer GS, Vrahas MS. Review of the pathophysiology and acute management of haemorrhage in pelvic fracture. Injury. 2006;37:602-613. DOI: 10.1016/j.injury.2005.09.007
35.Kuo LW, Yang SJ, Fu CY, Liao CH, Wang SY, Wu SC. Relative hypotension increases the probability of the need for angioembolisation in pelvic fracture patients without contrast extravasation on computed tomography scan. Injury. 2016;47:37-42. DOI: 10.1016/j.injury.2015.07.043
36.Fu CY, Wang SY, Liao CH, Kang SC, Hsu YP, Lin BC, Yuan KC, Ouyang CH. Computed tomography angiography provides limited benefit in the evaluation of patients with pelvic fractures. The American Journal of Emergency Medicine. 2014;32:1220-1224. DOI: 10.1016/j.ajem.2014.07.021
37.Mongan J, Rathnayake S, Fu Y, Gao DW, Yeh BM. Extravasated contrast material in penetrating abdominopelvic trauma: Dual-contrast dual-energy CT for improved diagnosis – preliminary results in an animal model. Radiology. 2013;268:738-742. DOI: 10.1148/radiol.13121267
38.McQuilten ZK, Wood EM, Bailey M, Cameron PA, Cooper DJ. Fibrinogen is an independent predictor of mortality in major trauma patients: A five-year statewide cohort study. Injury. 2017;48:1074-1081. DOI: 10.1016/j.injury.2016.11.021
39.Hayakawa M, Maekawa K, Kushimoto S, Kato H, Sasaki J, Ogura H, Matauoka T, Uejima T, Morimura N, Ishikura H, Hagiwara A, Takeda M, Kaneko N, Saitoh D, Kudo D, Kanemura T, Shibusawa T, Furugori S, Nakamura Y, Shiraishi A, Murata K, Mayama G, Yaguchi A, Kim S, Takasu O, Nishiyama K. High d-dimer levels predict a poor outcome in patients with severe trauma, even with high fibrinogen levels on arrival: A multicenter retrospective study. Shock. 2016;45:308-314. DOI: 10.1097/SHK.0000000000000542
40.Deras P, Villiet M, Manzanera J, Latry P, Schved JF, Capodevila X, Charbit J. Early coagulopathy at hospital admission predicts initial or delayed fibrinogen deficit in severe trauma patients. Journal of Trauma and Acute Care Surgery. 2014;77:433-440. DOI: 10.1097/TA.0000000000000314
41.Umemura T, Nakamura Y, Nishida T, Hoshino K, Ishikura H. Fibrinogen and base excess levels as predictive markers of the need for massive blood transfusion after blunt trauma. Surgery Today. 2016;46:774-779. DOI: 10.1007/s00595-015-1263-7
42.Yanagawa Y, Ishikawa K, Jitsuiki K, Yoshizawa T, Oode Y, Omori K, Ohsaka H. Fibrinogen degradation product levels on arrival for trauma patients requiring a transfusion even without head injury. World Journal of Emergency Surgery. 2017;8:106-109. DOI: 10.5847/wjem.j.1920-8642.2017.02.004
43.Hagiwara S, Aoki M, Murata M, Kaneko M, Ichikawa Y, Nakajima J, Isshiki Y, Sawada Y, Tamura J, Oshima K. FDP/fibrinogen ratio reflects the requirement of packed red blood cell transfusion in patients with blunt trauma. The American Journal of Emergency Medicine. 2017;35:1106-1110. DOI: 10.1016/j.ajem.2017.03.009
44.Lee DH, Lee BK, Noh SM, Cho YS. High fibrin/fibrinogen degradation product to fibrinogen ratio is associated with 28-day mortality and massive transfusion in severe trauma. European Journal of Trauma and Emergency Surgery. 2018;44:291-298. DOI: 10.1007/s00068-017-0844-0. Epub 2017 Sep 18
45.Nunez TC, Voskresensky IV, Dossett LA, Shinall R, Dutton WD, Cotton BA. Early prediction of massive transfusion in trauma: Simple as ABC (assessment of blood consumption)? The Journal of Trauma. 2009;66:346-352. DOI: 10.1097/TA.0b013e3181961c35
46.Yucel N, Lefering R, Maegele M, Vorweg M, Tjardes T, Ruchholtz S, Neugebauer EA, Wappler F, bouillon B, Rixen D, Polytrauma Study Group of the German Trauma Society. Trauma associated severe hemorrhage (TASH)-score: Probability of mass transfusion as surrogate for life threatening hemorrhage after multiple trauma. The Journal of Trauma. 2006;60:1228-1236. DOI: 10.1097/01.ta.0000220386.84102.bf
47.Schreiber MA, Perkins J, Kiraly L, Underwood S, Wade C, Holcomb JB. Early predictors of massive transfusion in combat casualties. Journal of the American College of Surgeons. 2007;205:541-545. DOI: 10.1016/j.jamcollsurg.2007.05.007
48.Rainer TH, Ho AM, Yeung JH, Cheung NK, Wong RS, Tang N, Ng SK, Wong GK, Lai PB, Graham CA. Early risk stratification of patients with major trauma requiring massive blood transfusion. Resuscitation. 2011;82:724-729. DOI: 10.1016/j.resuscitation.2011.02.016
49.Vandromme MJ, Griffin RL, McGwin Jr G, Weinberg JA, Rue 3rd LW, Kerby JD. Prospective identification of patients at risk for massive transfusion: An imprecise endeavor. The American Surgeon. 2011;77:155-161
50.Ogura T, Nakamura Y, Nakano M, Izawa Y, Nakamura M, Fujizuka K, Suzukawa M, Lefor AT. Predicting the need for massive transfusion in trauma patients: The traumatic bleeding severity score. Journal of Trauma and Acute Care Surgery. 2014;76:1243-1250. DOI: 10.1097/TA.0000000000000200
51.Ohmori T, Kitamura T, Ishihara J, Onishi H, Nojima T, Yamamoto K, Tamura R, Muranishi K, Matsumoto T, Tokioka T. Early predictors for massive transfusion in older adult severe trauma patients. Injury. 2017;48:1006-1012. DOI: 10.1016/j.injury.2016.12.028
52.Japan Resuscitation Council [Internet]. Part 2: Adult basic Life Support and Cardiopulmonary Resuscitation Quality. Japan Resuscitation Council Guideline. Available from: http://www.japanresuscitationcouncil.org/wpcontent/uploads/2016/04/0e5445d84c8c2a31aaa17db0a9c67b76.pdf (in Japanese) [Accessed: November 6, 2017]
53.Gando S, Kameue T, Nanzaki S, Nakanishi Y. Massive fibrin formation with consecutive impairment of fibrinolysis in patients with out-of-hospital cardiac arrest. Thrombosis and Haemostasis. 1997;77:278-282
54.Hagiwara S, Murata M, Kaneko M, Aoki M, Kanbe M, Ohyama Y, Tamura J, Oshima K. Usefulness of serum fibrin degradation products and d-dimer levels as biomarkers to predict return of spontaneous circulation in patients with cardiopulmonary arrest on arrival: Comparison with acid-base balance. Acute Medicine & Surgery. 2014;1:222-227. DOI: 10.1097/TA.0b013e31828cc967
55.Szymanski FM, Karpinski G, Filipiak KJ, Platek AE, Hrynkiewicz-Szymanska A, Kotkowski M, Opolski G. Usefulness of the D-dimer concentration as a predictor of mortality in patients with out-of-hospital cardiac arrest. The American Journal of Cardiology. 2013;112:467-471. DOI: 10.1016/j.amjcard.2013.03.057
56.Ono Y, Hayakawa M, Maekawa K, Kodate A, Sadamoto Y, Tominaga N, Murakami H, Yoshida T, Katabami K, Wada T, Sageshima H, Sawamura A, Gando S. Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients. Resuscitation. 2017;111:62-67. DOI: 10.1016/j.resuscitation.2016.08
Written By
Makoto Aoki, Shuichi Hagiwara and Kiyohiro Oshima
Submitted: 26 October 2017Reviewed: 19 March 2018Published: 05 November 2018
Open access peer-reviewed chapter
