A recurrent Gly43Asp substitution of coagulation Factor X rigidifies its catalytic pocket and impairs catalytic activity and intracellular trafficking

Background: Trauma is a global disease, with over 2.5 million deaths annually from hemorrhage and coagulopathy. Overt hyperfibrinolysis is rare in trauma, and is associated with massive fatal injuries. Paradoxically, clinical trials suggest a much broader indication for antifibrinolytics. Objective: To determine the incidence and magnitude of fibrinolytic activation in trauma patients and its relationship to clot lysis as measured by thromboelastometry. Methods: A prospective cohort study of 303 consecutive trauma patients admitted between January 2007 and June 2009 was performed. Blood was drawn on arrival for thromboelastometry (TEM) and coagulation assays. Follow-up was until hospital discharge or death. TEM hyperfibrinolysis was defined as maximum clot lysis of >15%. Fibrinolytic activation (FA) was deterined according to plasmin-antiplasmin (PAP) complex and D-dimer levels. Data were collected on demographics, mechanism, severity of injury, and baseline vital signs. The primary outcome measure was 28-day mortality. The secondary outcome measures were 28-day ventilator-free days and 24-h transfusion requirement. Results: Only 5% of patients had severe fibrinolysis on TEM, but 57% of patients had evidence of 'moderate' fibrinolysis, with PAP complex levels elevated to over twice normal (>1500μgL-1) without lysis on TEM. TEM detected clot lysis only when PAP complex levels were increased to 30 times normal (P<0.001) and antiplasmin levels were <75% of normal. Patients with FA had increased 28-day mortality as compared with those with no FA (12% vs. 1%, P<0.001), fewer ventilator-free days, and longer hospital stay. Conclusions: FA occurs in the majority of trauma patients, and the magnitude of FA correlates with poor clinical outcome. This was not detected by conventional TEM, which is an insensitive measure of endogenous fibrinolytic activity.