Abstract

Major haemorrhage is a leading cause of mortality and injury which accounts for approximately 4.4 million deaths each year globally. Acute traumatic coagulopathy is present in 1 in 4 trauma patients and is associated with an increase in major haemorrhage and a 5-fold increase in mortality. Finding effective therapies for major haemorrhage is critical to decrease mortality rates. In order to assess the likely clinical effectiveness of transfusion, the aim of this work was to develop an experimental model simulating the clot profile from a patient to explore potential products prior to clinical study. This model would be used to assess current and novel blood components developed to better treat trauma patients and potentially improve survival.
This in vitro model of acute traumatic coagulopathy (ATC model) was designed to simulate the hyperfibrinolytic phenotype often seen in trauma patients using thrombomodulin to activate the protein C pathway in healthy whole blood (WB) samples. The ATC model was used to evaluate the efficacy of thawed cryoprecipitate after 120 hours (an extension from 4 hours after which the unit is discarded) leading to a provisional specification for an extended post-thaw shelf-life cryoprecipitate component that was subsequently approved by the Joint United Kingdom Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee. A novel blood product aimed directly at trauma patients was also developed and evaluated. This blood product, termed platelet enhanced cryoprecipitate (PEC), contained a high concentration of fibrinogen and platelets. PEC was evaluated using the ATC model and numerous in vitro markers of quality. This component maintained positive haemostatic potential and markers of platelet quality and function throughout 14 days of storage at 22°C and 4°C and could be used to treat major haemorrhage resulting from trauma to improve patient outcome and survival.