Emergency. 2017; 5 (1), e58 OR I G I N A L RE S E A RC H Prevalence and Associated Factors of Acute Traumatic Co- agulopathy; a Cross Sectional Study Hojjat Derakhshanfar1, Ali Vafaei2, Ali Tabatabaey3∗, Shamila Noori4 1. Emergency Department, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Emergency Department, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Emergency Department, Shahid Beheshti Hospital, Qom University of Medical Sciences, Qom, Iran. 4. Pathology Department, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Received: December 2016; Accepted: February 2017; Published online: 24 February 2017 Abstract: Introduction: Acute traumatic coagulopathy (ATC) is defined as having evidence of coagulopathy in patients with severe trauma. The aim of this preliminary study was to assess the prevalence and associated factors of ATC in severely traumatic patients presenting to emergency department (ED). Methods: In this retrospective cross sectional study, all patients with severe traumatic injury and available coagulation profile, presenting to the EDs of two major trauma centers in Tehran, Iran, during one year, were studied. Rate of ATC was determined and the associations with various variables as well as outcome were analyzed using SPSS 21. Results: 246 patients with the mean age of 36.57±17.11 years were included (88.2% male). The mean injury severity score (ISS) was 21.83 ± 7.37 (16 – 54). Patients were resuscitated with 676.83 ± 452.02 (0 – 1500) ml intravenous fluid before arriving at the ED. The maximum and minimum frequencies of ATC were 31.3% based on PTT > 36s and 2.4% based on PT > 18s, respectively. There was a significant association between the occurrence of ATC (PT ratio > 1.2) and ISS > 23 (p = 0.001), abdominal abbreviated injury score (AIS) > 3 (p = 0.003), base deficit > 4 (p = 0.019), pulse rate > 90/minute (p = 0.041), and pH < 7.30 (p = 0.043). Conclusion: The frequency of ATC in the present series varied from 2.4% to 31.3% based on different ATC definitions. Abdominal AIS > 3 and base deficit > 4 were among the significant independent factors related to ATC occurrence based on stepwise logistic regression analysis. Keywords: Blood coagulation disorders; multiple trauma; risk factors; emergency service, hospital; outcome assessment © Copyright (2017) Shahid Beheshti University of Medical Sciences Cite this article as: Derakhshanfar H, Vafaei A, Tabatabaey A, Noori Sh. Prevalence and Associated Factors of Acute Traumatic Coagulopathy; a Cross Sectional Study. Emergency. 2017; 5(1): e58. 1. Introduction O ne third of trauma related deaths are due to hem- orrhage, which are generally preventable (1). Acute traumatic coagulopathy (ATC) is defined as having evidence of coagulopathy in patients with severe trauma on admission to emergency department (ED). The term ATC was first introduced in 2003 (2) and recent studies indi- cated that this abnormality is an endogenous phenomenon, which starts before any intervention (3). This characteristic separates this entity from the better known dilution coagu- lopathy or consumption coagulopathy in trauma patients. ∗Corresponding Author: Ali Tabatabaey; Emergency Department, Shahid Be- heshti hospital, Shahid Beheshti blv, Qom, Iran. Postal code: 3719964797 Tel: +98-25-36122000; Email: atabatabaey@muq.ac.ir It is estimated that up to 25% of severely injured patients have ATC. These patients have four-fold increased risk of mortality and significantly greater transfusion requirement (4). More importantly, it has been suggested that man- agement strategies targeting ATC may result in significant improvement of outcomes (1). Many attempts have been made for diagnosing ATC in the early minutes of admission to ED (1, 5, 6). Unfortunately, currently available laboratory methods do not have the capability of early ATC diagnosis. Therefore, researchers have sought to find clinical factors for early prediction of ATC occurrence, which is vital for initiation of lifesaving treatments (7, 8). Risk stratification of patients based on clinical findings and quick-available laboratory studies could help in early recognition of patients at risk for developing ATC. The aim of this preliminary study was to assess the prevalence and associated factors of ATC in This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com H. Derakhshanfar et al. 2 severely traumatic patients admitted to ED. 2. Methods 2.1. Study design and setting In this retrospective cross sectional study, the patients with severe traumatic injury presenting to the EDs of two major trauma centers in Tehran, Iran (Shohadye Tajrish and Imam Hossein Hospitals), during March 2013 to March 2014 were studied. This study was approved by the ethical commit- tee of Shahid Beheshti University of Medical Sciences, and the authors have done the study based on the declaration of Helsinki. 2.2. Participants The medical profiles of all patients with available coagulation panel samples, which were admitted to the trauma units of the mentioned hospitals during the study period, were ret- rospectively evaluated. All patients with severe injury were included. Severe injury was defined as Injury Severity Score (ISS) more than 15 (9). Patients less than 18 years old and subjects with history of bleeding disorder, severe liver dys- function, and using anticoagulation medications within the last two weeks were excluded. Moreover, in order to exclude patients at risk of dilution coagulopathy, those who had re- ceived more than 2 liters of fluids during transport and those who had been referred from other treatment centers were also excluded from the study. 2.3. Data gathering Demographic variables (age and gender), trauma mecha- nism, presenting vital signs (blood pressure, respiratory rate, pulse rate, temperature, O2 saturation), injured body parts, trauma severity based on ISS, laboratory findings (coagula- tion profile, cell blood count, and blood gas analysis), as well as in hospital outcomes of the patients (mortality, need for ICU admission, need for surgery, and need for blood transfu- sion) were extracted and collected from the patients’ profile using a predesigned checklist. Coagulation profile consisted of Prothrombin Time (PT), Partial Thromboplastin Time (PTT), PT ratio (patient PT/control PT), and International Normalization Ration (INR). A senior emergency medicine resident, under supervision of an emergency medicine spe- cialist, was responsible for review of patients’ medical profile and data gathering. 2.4. ATC Definition Previous studies have used different definitions for ATC. The current available definitions are: PT more than 18s, PTT more than 36s (5), PT ratio greater than 1.2 (1, 10), or International Normalization Ration (INR) greater than 1.5 (7, 8). All four Table 1: Baseline characteristics and outcome of the study popula- tion Variables Value Gender Male 216 (88.2) Female 29 (11.8) Mechanism of injury Pedestrian 33 (13.4) Motorcycle 83 (33.7) Car 48 (19.5) Rollover 20 (8.1) Falling 47 (19.1) Assault 10 (4.1) Others 5 (2.0) Transport to hospital Ambulance 173 (70.3) Unknown 10 (4.1) Self-admission 63 (25.6) Glasgow coma scale 15 146 (60.6) 8 - 15 74 (30.7) < 8 21 (8.7) Presenting Vital signs Systolic blood pressure (mmHg) 116.45 ± 17.74 Respiratory rate (/minutes) 17.63 ± 2.78 Pulse rate (/minutes) 89.46 ± 15.06 Saturation O2 9%) 94.38 ± 5.33 Temperature (c) 37.3 ± 0.40 Outcome Need for blood products 39 (15.9) Need for ICU admission 103 (42) Need for surgical intervention 192 (78) Mortality 20 (8.1) Data were presented as mean ± standard deviation or fre- quency and percentage. available definitions were used in the present study and the frequency of ATC was individually determined based on each of the mentioned definitions. A combination of the defini- tions was also considered, i.e. any patient who met any of the criteria was considered to have trauma related coagulopathy. 2.5. Statistical Analysis The data were analyzed using SPSS version 21 and presented as mean ± standard deviation (SD) or frequency and percent- age. The association between different ATC definitions and measured outcomes were evaluated. Then, the association between ATC occurrence (based on PT ratio > 1.2) and base- line variables was assessed. Continuous variables were com- pared using Mann-Whitney U test, and categorical data were analyzed using Chi-Square test. After recognition of statically significant variables, clinically relevant cut-points were as- signed to these variables to make their use more feasible in the clinical setting. Finally, logistic regression analysis was employed to determine the independent related factors of This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 3 Emergency. 2017; 5 (1), e58 ATC occurrence. 3. Results 3.1. Baseline characteristics 246 patients with the mean age of 36.57±17.11 (18 – 88) years were included (88.2% male). Table 1 shows the baseline char- acteristics and outcome of the study population. Motorcy- cle accidents were the most frequent mechanism of injury (33.7%) and 70.4% of patients had GCS 15 at the time of pre- senting to ED. The mean severity of injury based on ISS was 21.83 ± 7.37 (16 – 54). Patients were resuscitated with 676.83 ± 452.02 (0 – 1500) ml intravenous fluid before arriving at the ED. The mean duration of ED stay was 9.38 ± 9.83 (0.5 – 67) hours. 3.2. ATC (frequency and associations) Frequency of ATC based on different predefined definitions and its association with measured outcomes is presented in table 2. The maximum and minimum frequencies of ATC were 31.3% based on PTT > 36s and 2.4% based on PT > 18s, respectively. None of the definitions was able to predict in-hospital mortality. Table 3 summarizes the results of univariate analysis between ATC and different baseline variables. There was a significant correlation between the occurrence of ATC (PT ratio > 1.2) and ISS > 23 (p = 0.001), abdominal AIS > 3 (p = 0.003), base deficit > 4 (p = 0.019), pulse rate > 90 (p = 0.041), and pH < 7.30 (p = 0.043). Based on the results of a stepwise logistic regression analysis ab- dominal AIS > 3 (p = 0.001) and base deficit > 4 (p = 0.011) were independent related factors of ATC occurrence. 4. Discussion The frequency of ATC in the present series varied from 2.4% (PT > 18s) to 31.3% (PTT > 36s) based on different ATC definitions. Abdominal AIS > 3 and base deficit > 4 were among the significant independent related factors of ATC occurrence. A high prevalence of ATC has been reported in Uganda with 54% (5), while an Australian study found that only 9.0% of their traumatic patients met the definition of traumatic coagulopathy (8). Two studies from Europe have reported the prevalence of ATC in the range of 24% to 34% (2, 11). Most studies have shown a significant association be- tween the presence of ATC and mortality (2, 3, 5, 8, 12). This was not the case in this study. Neither the four definitions used for ATC, nor their combination, were able to predict mortality. We believe this was in part due to the low rate of mortalities in our study, which greatly limited its power to find an association between coagulation tests and mortality. Occurrence of ATC, successfully predicted the necessity for intensive care, and requirement of blood products trans- fusion. More transfusion and resuscitation requirements are other widely accepted predictable outcomes of ATC (7, 13, 14), yet they are not universal (5). In our study, having ATC would strongly predict higher transfusion requirements. Genetic factors are well-known contributors to the occur- rence of ATC (7, 11); so, the study of this phenomenon in different settings may further expand our understanding of the contributing factors. This has been a longtime interest of researchers since the coagulation profile is rarely made available in the early minutes of ED admission (1). In the absence of a rapid diagnostic tool, management of ATC is currently relying on suboptimal empirical transfusion strategies (14-17). In an attempt to predict the occurrence of ATC before availability of coagulation profile, Mitra et al. introduced the coagulopathy of severe trauma (COAST) score to help in early diagnosis of ATC. The researchers found that scores equal to or greater than 3 are predictive of ATC with appropriate sensitivity and specificity (8). In another study in Germany, Yucel et al. developed a more complicated scoring system aiming to predict ATC and the need for massive transfusion. In the Trauma Associated Severe Hemorrhage (TASH) score system, items such as hemoglobin, base excess, systolic blood pressure, heart rate, confirmed free intra-abdominal fluid, instable pelvic fracture, femur fracture, and male gender are contributing (18). A TASH score greater than 16 has been suggested as the cut-point for prediction of ATC. Other studies have also searched for clinical risk factors of ATC. Abdominal and thoracic trauma, pelvic fractures, mechanism of injury, and evidence of anemia and shock have been suggested as the risk factors for ATC (7, 19). The importance of male gender has also been emphasized (13, 20). In this study, although no association was found between ATC and gender, significant and independent associations were recognized with grade of abdominal trauma, and a base deficit greater than 4. This is in accordance with previous findings, which stated that coagulopathy is more prevalent when severe injury and hypo perfusion are co-existing (21-23). A prospective multi-center cohort study is suggested as the next step for evaluating ATC. 5. Limitation This was a preliminary attempt for estimating the prevalence and also recognizing the associated factors of ATC in Iran. The retrograde design of the study predisposes it to several limitations. The most important limitation was incomplete coverage of the target population and having missing data. We selected patients for whom a coagulation panel had been ordered by physicians in the primary order. We believe that since these tests are generally ordered for severely injured This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com H. Derakhshanfar et al. 4 Table 2: Association of acute traumatic coagulopathy occurrence and patients’ outcomes Variables Number (%) Outcomes Mortality ICU surgery Transfusion PT > 18s 6 (2.4) - - - + PTT > 36s 77 (31.3) - - + - PT ratio > 1.2 28 (11.4) - + - + INR > 1.5 27 (11) - + - + Combination 94 (38.2) - - + - PT: prothrombin time; PTT: partial thromboplastin time; INR: international normalized ratio; ICU: need to admission in intensive care unit; +: means statistically significant association. Table 3: Association of acute traumatic coagulopathy (ATC) occurrence and different baseline variables Variable ATC P With (n=28) Without (n=218) Male Gender 192 (88) 24 (86) 0.670 Age (year) 32.25 ± 13.74 37.12 ± 17.44 0.221 Transport time (minute) 42.30 ± 39.49 36.34 ± 28.70 0.824 Intravenous fluids (ml) 767.86 ± 419.04 665.14 ± 455.66 0.237 Injury severity score 25.75 ± 9.312 21.33 ± 6.95 0.017 Head and Neck AIS 1.71 ± 1.94 2.09 ± 1.90 0.365 Face AIS 0.57 ± 1.20 0.66 ± 1.13 0.519 Thorax AIS 1.07 ± 1.65 0.98 ± 1.44 0.996 Abdomen AIS 2.07 ± 1.96 1.03 ± 1.48 0.004 Extremities AIS 1.61±1.77 1.56 ± 1.80 0.884 External AIS 0.39 ± 0.86 0.14 ± 0.52 0.083 Presenting vital signs Glasgow coma scale 12.75±3.00 13.44±3.01 0.139 SBP (mmHg) 100.32±17.48 117.25±17.66 0.029 Respiratory rate (/minute) 95.07±12.58 88.73±15.23 0.004 Temperature (C) 37.00±0.32 37.04±0.42 0.905 Respiratory rate (/minute) 18.68±4.25 17.49±2.52 0.199 O2 Saturation in the ED 92.70±4.94 94.59±5.36 0.014 Laboratory findings Serum pH 7.31±0.13 7.38±0.12 0.044 PaCO2 (mmHg) 40.85±14.62 39.92±11.17 0.788 HCO3 19.91±5.62 23.88±8.67 0.047 Base deficit 5.47±5.61 1.41±6.99 0.026 White blood cell (103/µL) 14.03±5.17 12.15k±4.59 0.034 Platelet count (103/µL) 170.18±88.32 192.53±84.87 0.119 Hemoglobin (mg/dl) 11.51±2.69 12.12±2.79 0.230 Data were presented as mean ± standard deviation or number and percentage. AIS: Abbreviated Injury Score; SBP: systolic blood pressure. patients and those who require operative interventions, we most likely have not missed a large portion of our target pop- ulation. The low rate of mortality in our studied sample might be owing to selection bias; in which the test results of patients with early mortality might not have been included in their medical profile, leading to elimination from this study. Another more possible explanation for the low reported mor- tality might be a high incidence of pre-hospital mortality. It has been reported that, in developing countries, more than 70% of deaths due to injuries occur on the scene (21). In such settings most early mortalities never reach hospital-based studies. 6. Conclusion The frequency of ATC in the present series varied from 2.4% (PT > 18s) to 31.3% (PTT > 36s) based on different ATC defini- tions. Abdominal AIS > 3 and base deficit > 4 were among the significant independent factors related to ATC occurrence based on stepwise logistic regression analysis.This reinforces the concept that acute traumatic coagulopathy is triggered when severe injury and hypoperfusion coexist. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 5 Emergency. 2017; 5 (1), e58 7. Appendix 7.1. Acknowledgements This work has been excerpted from the residency thesis num- ber 216, by Ali Tabatabaey MD, supervised by Hojjat Der- akhshanfar MD at the school of medicine, Shahid Beheshti University of Medical Sceinces, Tehran, Iran. 7.2. Author’s contribution All authors passed four criteria for authorship contribution based on recommendations of the International Committee of Medical Journal Editors. 7.3. Funding/Support None. 7.4. Conflict of interest None. References 1. Davenport R, Manson J, De’Ath H, Platton S, Coates A, Allard S, et al. Functional definition and characteriza- tion of acute traumatic coagulopathy. Crit Care Med. 2011;39:2652-8. 2. Brohi K, Singh J, Heron M, Coats T. Acute traumatic coag- ulopathy. The Journal of trauma. 2003;54(6):1127-30. 3. Floccard B, Rugeri L, Faure A, Saint Denis M, Boyle EM, Peguet O, et al. Early coagulopathy in trauma pa- tients: an on-scene and hospital admission study. Injury. 2012;43:26-32. 4. Mitra B, Cameron Pa, Mori A, Fitzgerald M. Acute co- agulopathy and early deaths post major trauma. Injury. 2012;43:22-5. 5. Mujuni E, Wangoda R, Ongom P, Galukande M. Acute traumatic coagulopathy among major trauma patients in an urban tertiary hospital in sub Saharan Africa. BMC Emerg Med. 2012;12:16. 6. Rugeri L, Levrat A, David JS, Delecroix E, Floccard B, Gros A, et al. Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography. Journal of thrombosis and haemostasis : JTH. 2007;5(2):289-95. 7. Maegele M. Acute traumatic coagulopathy: Incidence, risk stratiïňĄcation and therapeutic options. World jour- nal of Emergency Medicine. 2010;1:12-21. 8. Mitra B, Cameron PA, Mori A, Maini A, Fitzgerald M, Paul E, et al. Early prediction of acute traumatic coagulopathy. Resuscitation. 2011;82(9):1208-13. 9. Copes WS, Champion HR, Sacco WJ, Lawnick MM, Keast SL, Bain LW. The Injury Severity Score revisited. The Jour- nal of trauma. 1988;28:69-77. 10. Frith D, Goslings JC, Gaarder C, Maegele M, Cohen MJ, Allard S, et al. Definition and drivers of acute traumatic coagulopathy: Clinical and experimental investigations. Journal of Thrombosis and Haemostasis. 2010;8:1919-25. 11. Maegele M, Paffrath T, Bouillon B. Acute traumatic co- agulopathy in severe injury: incidence, risk stratifica- tion, and treatment options. Deutsches Arzteblatt inter- national. 2011;108:827-35. 12. Frith D, Davenport R, Brohi K. Acute traumatic co- agulopathy. Current opinion in anaesthesiology. 2012;25:229-34. 13. Brown J, Cohen M, Minei J. Characterization of Acute Coagulopathy and the Gender Dimorphism Post-Injury: Females and Coagulopathy Just Don’t Mix. Journal of trauma and acute care surgery. 2012;73:1395-400. 14. Mitra B, Cameron Pa, Gruen RL. Aggressive fresh frozen plasma (FFP) with massive blood transfusion in the absence of acute traumatic coagulopathy. Injury. 2012;43:33-7. 15. Armand R, Hess JR. Treating coagulopathy in trauma pa- tients. Transfus Med Rev. 2003;17:223-31. 16. Hess JR, Hiippala S. Optimizing the use of blood products in trauma care. Critical care (London, England). 2005;9 Suppl 5:S10-4. 17. Schochl H, Maegele M, Solomon C, Gorlinger K, Voel- ckel W. Early and individualized goal-directed therapy for trauma-induced coagulopathy. Scandinavian Jour- nal of Trauma, Resuscitation and Emergency Medicine. 2012;20:15. 18. YÃijcel N, Lefering R, Maegele M, Vorweg M, Tjardes T, Ruchholtz S, et al. Trauma Associated Severe Hemor- rhage (TASH)-Score: probability of mass transfusion as surrogate for life threatening hemorrhage after multiple trauma. The Journal of trauma. 2006;60:1228-36; discus- sion 36-7. 19. Nunez TC, Voskresensky IV, Dossett LA, Shinall R, Dut- ton WD, Cotton BA. Early prediction of massive transfu- sion in trauma: simple as ABC (assessment of blood con- sumption)? The Journal of trauma. 2009;66(2):346-52. 20. Brown JB, Cohen MJ, Minei JP, Maier RV, West MA, Bil- liar TR, et al. Characterization of acute coagulopathy and sexual dimorphism after injury: females and coagulopa- thy just do not mix. The journal of trauma and acute care surgery. 2012;73:1395-400. 21. Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet JF. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C path- way? Annals of surgery. 2007;245(5):812-8. 22. Brohi K, Cohen MJ, Ganter MT, Schultz MJ, Levi M, Mack- ersie RC, et al. Acute coagulopathy of trauma: hypop- erfusion induces systemic anticoagulation and hyperfib- rinolysis. The Journal of trauma. 2008;64(5):1211-7; dis- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com H. Derakhshanfar et al. 6 cussion 7. 23. Ganter MT, Pittet J-F. New insights into acute coagulopa- thy in trauma patients. Best practice & research Clinical anaesthesiology. 2010;24:15-25. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com Introduction Methods Results Discussion Limitation Conclusion Appendix References