Acute traumatic coagulopathy

Massive haemorrhage remains a leading cause of mortality post injury worldwide. Traditional methods of resuscitation that used large volumes of crystalloids followed by packed red blood cells with delayed consideration of impaired coagulation may be harmful. In response, trauma centres have initiated massive transfusion guidelines or protocols to guide resuscitation of haemorrhagic shock. This thesis starts with an evaluation of the effectiveness of massive transfusion guidelines to guide initial trauma resuscitation. A weak association of massive transfusion guidelines with improved patient outcomes is demonstrated, with reasons behind any improvement remaining elusive. To define this problem further, a standardised definition of massive transfusion has been developed, one most applicable to the acute care setting. Using this clinically useful definition, the subgroup of patients requiring massive transfusion remained difficult to predict and the level of evidence for current guidelines was shown to be low, incorporating multiple biases and confounders. Upon attempting to correct for these limitations, conclusions different to those guiding the composition of current massive transfusion guidelines were evident. A small proportion of major trauma patients have impaired coagulation- most likely commencing at the scene of trauma and well established upon presentation to hospital. The implications of this acute traumatic coagulopathy (ATC) during trauma resuscitation in being associated with early death are highlighted and despite overall improvements in patient outcomes post trauma in the last decade, outcome in the critically ill subgroup of patients with ATC remain relatively unchanged. Trauma patients most likely to benefit from massive transfusion guidelines are those with ATC and in the absence of ATC, proactive administration of high volumes of plasma, as guided by current massive transfusion guidelines, were not associated with any survival benefit, while exposing patients to the adverse effects of plasma. One of the reasons for this lack of progress in improving outcome in patients with ATC has been the inability to select a sufficient sample of patients with ATC into a study population. As ATC is relatively uncommon (about 8% of all major trauma patients), inclusion criteria of previous studies had selected only a small proportion of those with ATC resulting in studies being underpowered for the effect size being measured. To bridge this gap, a pre-hospital physiological scoring system to enrol patients into prospective trials with a high specificity is presented and subsequently prospectively validated. The usefulness of the score to recruit a high proportion of patients with ATC is further demonstrated in a prospective comparative study. In planning for future studies, this thesis discusses the limitations of current randomised controlled trials in directing management of ATC and highlighted reasons as to why, despite level I evidence, the uptake of these agents into massive transfusion guidelines have been poor. Acute traumatic coagulopathy is a complex entity, increasing in complexity through new discoveries, and is unlikely to be reversed by a single treatment. Rather, development of effective trauma systems and management guidelines that incorporate multiple agents evaluated through robust clinical trials should be the target of further research. The research design of a multi-centre prospective randomised controlled study, developed using the findings of this thesis, is presented.