Clot life span model analysis of clot growth and fibrinolysis in normal subjects: Role of thrombin activatable fibrinolysis inhibitor

Hypofibrinolysis plays a role in thrombophilic states, and a thrombelastography-based method incorporating tissue-type plasminogen activator to determine vulnerability to fibrinolytic stress has recently been developed. This study proposed to kinetically define fibrinolytic vulnerability and the contribution of thrombin activatable fibrinolysis inhibitor to fibrinolytic defenses in normal subjects. Plasma from 30 normal subjects was exposed to tissue factor/kaolin and tissue-type plasminogen activator (100 IU/ml). Prior to activation of coagulation, samples were either not exposed or exposed to potato carboxypeptidase inhibitor (25 μg/ml, a thrombin activatable fibrinolysis inhibitor). Data were collected until clot lysis time was observed. In plasma, time to onset of maximum rate of fibrinolysis was 200-1125 s (95% confidence interval), maximum rate of lysis was -2.0 - 0.8 dynes/cm per s, and clot lysis time was 555-1595 s. Thrombin activatable fibrinolysis inhibitor's inhibition decreased the time to onset of maximum fibrinolysis by 45%, increased the rate of maximum lysis by 50%, and decreased clot lysis time by 45%. The study established a range of fibrinolytic kinetic values and the contribution of thrombin activatable fibrinolysis inhibitor in normal subjects. Study of disease states involving potential hypofibrinolysis (e.g., in-situ ventricular assist device, cancer) could be conducted using this system to link fibrinolytic vulnerability and thrombophilia.