PLASMA TAFI LEVELS INFLUENCE THE CLOT LYSIS TIME IN HEALTHY-INDIVIDUALS IN THE PRESENCE OF AN INTACT INTRINSIC PATHWAY OF COAGULATION

Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a recently ident ified fibrinolysis inhibitor in plasma, that when converted to an enzy me potently attenuates fibrinolysis. It is activated by relatively hig h concentrations of thrombin that exceed the thrombin concentration re quired for fibrin formation. These high concentrations of thrombin are generated by the intrinsic pathway via activation of factor XI by thr ombin. The down regulation of fibrinolysis by TAFI can be measured in a clot lysis assay. When the clot lysis times of healthy individuals w ere determined, large inter-individual differences were observed. To d etermine if differences in concentration of TAFI explain the variation in clot lysis between individuals, specific assays were developed for the measurement of TAFI antigen and activity in plasma. In normal pla sma, there was a dose-dependent relationship between TAFI antigen and TAFI activity. There was also a correlation between clot lysis time an d plasma TAFI antigen, indicating that the amount of TAFI that is acti vated during the clot lysis assay, is dependent on the concentration o f TAFI. In the plasmas of 20 healthy individuals, clot lysis times, TA FI antigen and TAFI activity were determined. Both TAFI antigen and TA FI activity showed a significant correlation with the clot lysis time. No correlation between TAFI antigen and clot lysis time was found whe n the clot lysis time was determined in the presence of an antibody bl ocking the factor XI feedback loop. These results indicate that plasma TAFI levels influence the clot lysis time in healthy individuals in t he presence of an intact intrinsic pathway of coagulation.