Hypercoagulability Is Most Prevalent Early after Injury and in Female Patients Martin A. Schreiber, MD, Jerome Differding, BS, Per Thorborg, MD, John C. Mayberry, MD, and Richard J. Mullins, MD Background: Hypercoagulability af- ter injury is a major source of morbidity and mortality. Recent studies indicate that there is a gender-specific risk in trauma patients. This study was performed to de- termine the course of coagulation after injury and to determine whether there is a gender difference. We hypothesized that hypercoagulability would occur early af- ter injury and that there would be no dif- ference between men and women. Methods: This was a prospective co- hort study. Inclusion criteria were admis- sion to the intensive care unit, Injury Se- verity Score > 4, and the ability to obtain consent from the patient or a relative. A Thrombelastograph (TEG) analysis was performed and routine coagulation pa- rameters and thrombin-antithrombin complexes were measured within 24 hours of injury and then daily for 4 days. Results: Sixty-five patients met crite- ria for entry into the study. Their mean age was 42  17 years and their mean Injury Severity Score was 23  12. Forty patients (62%) were men. The prevalence of a hypercoagulable state by TEG was 62% on day 1 and 26% on day 4 (p < 0.01). Women were significantly more hy- percoagulable on day 1 than men as mea- sured by the time to onset of clotting (women, 2.9  0.7 minutes; men, 3.9  1.5 minutes; p < 0.01; normal, 3.7– 8.3 min- utes). Mean platelet counts, international normalized ratios, and partial thrombo- plastin times were within normal limits throughout the study. Thrombin activa- tion as measured by thrombin-antithrom- bin complexes decreased from 34  15 g/L on day 1 to 18  8 g/L (p < 0.01) on day 4, consistent with the prevalence of hypercoagulability by TEG. Conclusion: Hypercoagulability af- ter injury is most prevalent during the first 24 hours. Women are more hyperco- agulable than men early after injury. The TEG is more sensitive than routine coag- ulation assays for the detection of a hyper- coagulable state. Key Words: Hypercoagulable state, Thrombelastogram, Gender, Thrombin activation, Thrombosis. J Trauma. 2005;58:475–481. T he hypercoagulable state that follows traumatic injury is integral to limiting hemorrhage, but excessive thrombo- sis is associated with significant late morbidity and mor- tality. Untreated trauma patients undergoing routine venog- raphy have been found to have a 58% incidence of thromboembolic events. 1 The onset of adult respiratory dis- tress syndrome and multiple organ failure after trauma have also been associated with a hypercoagulable state character- ized by elevated tissue factor levels. 2,3 Fibrin deposition within the alveolar compartment occurs in adult respiratory distress syndrome. 4,5 Activated protein C, a potent anticoag- ulant and profibrinolytic agent, is currently the only agent that has been shown to improve outcome in septic patients who develop multiple organ failure. 6 Data from animal studies indicate that male gender is a risk factor for death after hemorrhage and sepsis. 7,8 Human studies of gender dimorphism after trauma have produced conflicting results. Although some studies have shown no gender differences in outcomes, other studies have shown survival advantages for women below the age of 50. 9 –12 Although the cause of improved outcome among women is not known, the presence of relatively high levels of estrogen results in a hypercoagulable state that might be beneficial early after injury in bleeding patients. 13–16 Despite the critical impact of a hypercoagulable state on trauma patients, routine coagulation assays are not useful in its detection. The Thrombelastograph (TEG) analyzer pro- vides a comprehensive functional evaluation of overall coag- ulation status and has the added advantage that it can be performed at the bedside. Kaufmann et al. reported that the majority of trauma patients undergoing TEG analysis during their initial evaluation are hypercoagulable. 17 Serial coagula- tion analyses using the TEG and comparisons between men and women have not been previously published. The purpose of this study was to determine the time course of coagulation changes over 4 days in critically injured trauma patients and to determine whether there is a difference between men and women. We also sought to compare routine coagulation pa- rameters to the TEG. We hypothesized that hypercoagulabil- ity would occur early after injury and there would be no gender differences. Submitted for publication November 8, 2004. Accepted for publication November 22, 2004. Copyright © 2005 by Lippincott Williams & Wilkins, Inc. From Oregon Health & Science University, Portland, Oregon. Supported by Public Health Service grant 5 M01 RR000334. Presented at the 63rd Annual Meeting of the American Association for the Surgery of Trauma, September 29 –October 2, 2004, Maui, Hawaii. Address for reprints: Martin A. Schreiber, MD, FACS, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Mail Code L223A, Portland, OR 97239; email: schreibm@ohsu.edu. DOI: 10.1097/01.TA.0000153938.77777.26 The Journal of TRAUMA  Injury, Infection, and Critical Care Volume 58 • Number 3 475