HUMAN THROMBIN AND CALCIUM BOUND FACTOR XA SIGNIFICANTLY SHORTEN TPA-INDUCED FIBRIN CLOT LYSIS TIME VIA NEUTRALIZATION OF PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 ACTIVITY

Employing a fibrin clot lysis assay, we reassessed the significance of the neutralization of plasminogen activator inhibitor type 1 (PAI-I) activity by thrombin and factor-Xa in fibrinolysis. When PAI-I enriche d fibrin clots were formed using increasing concentrations of thrombin (0.1, 0.5, 1.0 IU/ml), their lysis times became shorter (43.8 +/- 4.9 , 25.7 +/- 3.7, 13.9 +/- 0.8 h respectively). Times were shortened fur ther by either heparin (43.9 +/- 11.0, 12.1 +/- 2.6, 3.6 +/- 0.2 h res pectively) or vitronectin (17.0 +/- 1.6, 1.9 +/- 0.7, 0.9 +/- 0.0 h re spectively). Factor-Xa together with Ca++ shortened the clot lysis tim e further. Fibrin autography revealed that both enzymes dose dependent ly interfered with complex formation between tPA and PAI-1, making lar ge amounts of tPA remaining to be free form. The mechanism seems to pl ay a role in the coagulation associated enhancement of fibrinolysis.