Serial Changes in Coagulant Activities After Thrombolytic Therapy for Acute Myocardial Infarction

Abstract

Early reocclusion and bleeding complications are still unresolved problems in thrombolytic therapy for acute myocardial infarction (AMI). In the present study, 16 patients treated with either fibrin-specific tissue-type plasminogen activator (t-PA) or nonspecific urokinase (UK) were studied to determine the effects of thrombolytic therapy on serial hemostatic states. Hemostatic states of each patient were estimated by measuring various plasma markers at one- to two-hour intervals during the first six hours of therapy, daily during the next three days, and subsequently on day 7. Two markers of plasma thrombin generation, thrombin antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F 1 + 2), showed an activated coagulant state immediately after thrombolytic therapy. The amount of thrombin generation indicated by these markers showed significant positive correlation with direct markers of fibrinolysis such as fibrin degradation products (FDP), while it did not show any correlation with the markers for plasmin generation. The potential for coagulation as indicated by prothrombin time (%) decreased with thrombolysis using fibrin nonselective agents, owing perhaps to destruction of coagulant factors by free plasmin. Fibrinolytic activity induced by thrombolytic therapy for AMI caused transient activation of the coagulant system, which could contribute to early reocclusion. Fibrin nonselective agents decreased the potential for coagulation by destroying clotting factor through the generation of free plasmin. These data provide theoretical support for simultaneous administration of anticoagulant therapy with fibrin-specific thrombolytic agents.

Thrombolytic Therapy in Acute Myocardial Infarction

“…31 In a limited number of patients with AMI, an association between TAT and markers of fibrinolytic activity independent of the thrombolytic regimen was described. 6 Our data indicate that both streptokinase and alteplase activate the kallikrein-kinin system in accordance with the difference in procoagulant action (thrombin activation) of both regimens. It supports the in vitro findings with respect to kallikrein stimulation with plasmin.…”

“…The use of alteplase reveals similar findings: Levels of TAT complexes, prothrombin fragment 1ϩ2, and fibrinopeptide A 3,6,8,10,11,18 are higher, along with a reduction in fibrinogen and an increase in D-dimers. High thrombin activation markers are reported to be associated with failure of lysis 18 but not with worse clinical outcome.…”

Prolonged Activation of Fibrinolytic System Induced by Fibrin Nonselective Thrombolytic Agent Can Contribute to Preventing Early Reocclusion after Coronary Thrombolytic Therapy

“…10], which might be one of the causes of early reocclu sion. However, we found no difference in thrombin production whether those patients received fibrin-specific or -nonspecific throm bolytic agents [10], We also reported that not only fibrin-specific t-PA but also fibrin-non specific urokinase enhanced platelet aggrega tion [11], In the present study, we focused on the duration of fibrinolytic activity induced by either fibrin-specific or non-specific thrombolytic agents. Theoretically, fibrinspecific thrombolytic agents first bind to fi brin, then cause fibrinolysis limited to the thrombus itself, without generating circulat ing free plasmin [12].…”

“…Early reperfusion by coronary thrombo lytic therapy not only preserved left ventricu lar systolic function [ 13] but also reduced the mortality of acute myocardial infarction [14,15]. We could improve the efficacy if we could control early reocclusion by some opti mal strategy.…”

“…Theoretically, fibrinspecific thrombolytic agents first bind to fi brin, then cause fibrinolysis limited to the thrombus itself, without generating circulat ing free plasmin [12]. However, fibrin nonselective agents such as urokinase cannot bind to fibrin selectively, so they caused fibrinoly sis only after the generation of free circulating plasmin [13]. The duration of fibrinolytic ac tivity is hard to estimate because the exact inactivation pathway of this circulating free plasmin is still unclear.…”