Effects of recombinant activated Factor VII and supplementary oxygen on coagulopathy after trauma

Abstract

Approximately 30 – 40% of severely injured civilian and military casualties develop acute coagulopathy before arrival into hospital, with significant clinical implications such as increased mortality. The aetiology of trauma coagulopathy is multifactorial and thought to include consumption of clotting factors, acidosis and haemodilution. More recently attention has focussed on the role of tissue hypoperfusion and shock in the development of acute trauma coagulopathy. Coagulopathy is currently managed by the early use of blood products with or without adjuncts such as antifibrinolytics, and procoagulant agents. This can be guided by repeated assessment of clotting status to monitor the effects of therapy e.g. using TEG® or ROTEM®. Work presented in this thesis demonstrates the value of using interim values of coagulation, to accelerate the assessment of coagulation. ROTEM® A10 predicted coagulopathy with a sensitivity/specificity of 1.0/0.7, nineteen minutes earlier than running the test to completion. In a randomised controlled trial in terminally anaesthetised pigs the implications of clinical treatment of coagulopathy were assessed. The implications of administering early oxygen or rFVIIa on coagulation were compared in a model of complex battlefield trauma. The administration of intravenous rFVIIa conferred a “boost” in clotting, however it was followed by an exaggerated deterioration in coagulation. By contrast coagulation was better maintained in the group treated with oxygen. A second, or delayed dose of rFVIIa was simulated in an in vitro study where blood from these groups was spiked with rFVIIa. In the animals treated with intravenous rFVIIa, the effect of the second dose was attenuated, while a comparable dose had a greater effect in the oxygen group. ii These findings have implications for austere, resource constrained military settings since a boost in clotting might reduce immediate blood loss. However, this needs to be balanced against the loss of responsiveness over time. Limiting shock with oxygen may have a greater long term potential should evacuation be delayed.