Human Thrombin and Calcium Bound Factor Xa Significantly Shorten tPA-Induced Fibrin Clot Lysis Time via Neutralization of Plasminogen Activator Inhibitor Type 1 Activity

Tetsumei Urano; Nobuo Nagai; Megumi Matsuura; Hayato Ihara; Yumiko Takada; Akikazu Takada

doi:10.1055/s-0037-1615156

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 80(01): 161-166
DOI: 10.1055/s-0037-1615156

Rapid Communication

Schattauer GmbH

Human Thrombin and Calcium Bound Factor Xa Significantly Shorten tPA-Induced Fibrin Clot Lysis Time via Neutralization of Plasminogen Activator Inhibitor Type 1 Activity

Tetsumei Urano

¹Departments of Physiology and Pathophysiology

,

Nobuo Nagai

¹Departments of Physiology and Pathophysiology

,

Megumi Matsuura

¹Departments of Physiology and Pathophysiology

,

Hayato Ihara

¹Departments of Physiology and Pathophysiology

,

Yumiko Takada

²Hamamatsu University, School of Medicine, Hamamatsu, Shizuoka, Japan

,

Akikazu Takada

¹Departments of Physiology and Pathophysiology

› Author Affiliations

Abstract

Summary

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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References

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