Prehospital blood transfusion after combat injury and platelet function in an animal model of complex military trauma

Abstract

The management of trauma has been transformed by recent conflict and by improvements in understanding of the response to injury, particularly coagulopathy. Clotting abnormalities can appear early after trauma and have multiple causes, including tissue injury, shock and the effects of treatment. There is increasing understanding of the contribution of coagulation molecules to these abnormalities. Platelets are recognised as being central to the clotting cascade in the current cell-based model of coagulation but have been incompletely studied after traumatic injury. There has been widespread adoption of the practice of “haemostatic resuscitation” using blood products rather than crystalloid fluids with a high ratio of plasma to red blood cells to correct the coagulopathy of trauma while restoring the patient’s physiology. The British Armed Forces have pushed this forward of the hospital using physician-led medical teams. However, this practice has unquantified benefit and potential for harm, and is a logistical challenge. The first study in this thesis assesses whether available clinical data support the use of prehospital transfusion. It compared recipients of the treatment with similarly injured controls. Although mortality was halved, confounding changes in hospital transfusion practice made it impossible to rely on these data to establish the efficacy of prehospital transfusion. To allow further study, an animal model of complex military trauma was developed. The author focused on developing a flow cytometry assay for the assessment of platelet activation and response to in vitro stimulation. This was successful. The performance of the assay was assessed in the context of the animal model. Surgical preparation of the model appeared to affect the expression of the relevant activation marker. While the assay proved incompatible with unavoidable constraints of the model, its development acted as the basis for the establishment of a human platelet study of combat casualties in Afghanistan.