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 (>1500\u3bcgL-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