A PROACTIVE APPROACH TO THE COAGULOPATHY OF TRAUMA: THE RATIONALE AND GUIDELINES FOR TREATMENT E Kirkman, S Watts, T Hodgetts, P Mahoney, S Rawlinson, M Midwinter © Crown copyright 2008. Published with the permission of the Defence Science and Technology Laboratory on behalf of the Controller of HMSO Corresponding Author: Dr Emrys Kirkman PhD Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK E: EKIRKMAN@dstl.gov.uk Introduction An emerging concept in combat casualty care is that of haemostatic resuscitation: the rapid and proactive treatment of the coagulopathy associated with major injury. This article reviews the evidence behind this approach and demonstrates how this is used pragmatically in contemporary combat casualty care practice. Prevalence of coagulopathy in trauma According to the British Committee for Standards in Haematology and the American College of Pathologists, prolongation of the activated partial thromboplastin time (APTT) and prothrombin time (PT) to 1.5 times the mean normal value indicates a coagulopathy requiring blood product replacement [1-3]. A number of studies have indicated that coagulopathy is common after severe trauma and that it results from a number of causes including metabolic acidosis, hypothermia, dilution of coagulation factors by resuscitation fluids and consumption of coagulation factors [4-10]. Coagulopathy is especially associated with some forms of injury, e.g. brain injury, because of the release of tissue thromboplastins from damaged brain matter [11; 12]. A UK civilian study by Brohi et al [13], using the definitions given above, clearly demonstrated that major trauma patients (Injury Severity Score, ISS >15) can present at hospital with a coagulopathy: 24% of 1088 trauma patients (median ISS 20) analyzed on arrival at the Emergency Department (ED) were coagulopathic. The majority (75%) of patients had suffered blunt trauma and the median time from injury to hospital was 73 minutes; this is compared to 7.6% blunt force (motor vehicle crash, fall, assault, crush) in 876 patients on the UK military Joint Theatre Trauma Registry (01 April 2006 to 30 September 2007, OP HERRICK and OP TELIC only), and a median injury to ED handover time of 97 minutes for UK military priority 1 casualties [14]. The incidence of coagulopathy increased with severity of injury (assessed by ISS), independent of the volume of pre-hospital resuscitation fluid (reliably recorded by a physician). The authors comment that the patients had received minimal pre-hospital fluid resuscitation (median values of 500 ml crystalloid or 1000 ml colloid) and that the development of coagulopathy in these patients was unrelated to the volume or type of intravenous fluid given. A second survey [15] based on 8724 severely injured patients (96% blunt injuries) from the German Trauma Registry Database confirms the presence of coagulopathy in 34% of all severely injured patients arriving in the Emergency Department. This study used a similar definition of coagulopathy to that employed by Brohi et al [13] and identified a similar time to hospital. The presence of coagulopathy was positively associated with the volume of pre-hospital fluid, injury severity and delay between injury and arrival at hospital [15]. Even in patients with minimal pre-hospital resuscitation, coagulopathy was present in 10% of cases [15]. Despite the limited statistical analysis in this study it supports the conclusion that coagulopathy is present in a significant proportion of severely-injured patients by the time they arrive at hospital. Early coagulopathy was also reported by MacLeod et al [16] in a retrospective analysis of 7638 trauma patients admitted to a Level 1 Trauma Centre between Jan 1995 and Dec 2000, although as a group these patients were less severely injured (median ISS 9) than those described by Brohi et al [13]. Additionally, MacLeod et al [16] were unable to account for medication that might have contributed to the coagulopathy, for example warfarin treatment or pre-hospital fluid administration. A number of other smaller studies [17; 18] and anecdotal comments [19]] have also documented coagulopathy in trauma patients on arrival at hospital. Furthermore, early coagulopathy is associated with increased morbidity and mortality [13; 15; 16; 18]. Although it is always a concern that studies with negative conclusions are less likely to be published than those with a positive conclusion, the collective evidence strongly suggests that a proportion of severely injured patients are already coagulopathic by the time they arrive in the Emergency Department and the remainder are at high risk of rapidly developing a coagulopathy. Clearly the true incidence of coagulopathy will depend on the definition adopted. There is evidence that bleeding time and thromboelastographic measurements are better indicators of dilutional and hypothermia induced coagulopathy [20]. Using this methodology the true incidence of coagulopathy associated with major trauma may well be significantly higher than reported. Proactive treatment of coagulopathy in severely injured casualties The coagulopathy seen early in trauma patients is multi- factorial and includes hypothermia, acidosis, severity of injury and prolonged hypotension [21; 22]. However, it has been shown that coagulopathy can occur very early after injury where these mechanisms are not necessarily present. Novel mechanisms associated with tissue hypoperfusion [23] and mediated through activation of protein C causing CLINICAL DEVELOPMENTS 302 JR Army Med Corps 153(4): 302-306