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  • Title: Human thrombin and calcium bound factor Xa significantly shorten tPA-induced fibrin clot lysis time via neutralization of plasminogen activator inhibitor type 1 activity.
    Author: Urano T, Nagai N, Matsuura M, Ihara H, Takada Y, Takada A.
    Journal: Thromb Haemost; 1998 Jul; 80(1):161-6. PubMed ID: 9684803.
    Abstract:
    Employing a fibrin clot lysis assay, we reassessed the significance of the neutralization of plasminogen activator inhibitor type 1 (PAI-1) activity by thrombin and factor-Xa in fibrinolysis. When PAI-1 enriched 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 further by either heparin (43.9 +/- 11.0, 12.1 +/- 2.6, 3.6 +/- 0.2 h respectively) or vitronectin (17.0 +/- 1.6, 1.9 +/- 0.7, 0.9 +/- 0.0 h respectively). Factor-Xa together with Ca++ shortened the clot lysis time further. Fibrin autography revealed that both enzymes dose dependently interfered with complex formation between tPA and PAI-1, making large amounts of tPA remaining to be free form. The mechanism seems to play a role in the coagulation associated enhancement of fibrinolysis.
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