Intracranial Hemorrhage After Coronary Thrombolysis with Tissue Plasminogen Activator

Abstract

The thrombolytic agent recombinant tissue-type plasminogen activator (rt- PA) produces clot lysis by catalyzing the conversion of plasminogen into plasmin [15]. In the coronary circulation, this effect is followed in 70%– 89% of cases by reperfusion of occluded arteries, which in turn results in improved ventricular function and survival as compared with untreated controls [2, 31]. The relative clot-specificity of rt-PA as compared with other thrombolytic agents (such as streptokinase and urokinase) determines a lesser degree of activation of circulating plasminogen, as well as decreased degradation of factors V, VIII, and fibrinogen by this agent [32]. This property is responsible for a lower hemorrhagic potential for rt-PA. Despite this advantage over streptokinase and urokinase, rt-PA use results in hemorrhagic complications, both systemic and intracranial, that partially limit its clinical usefulness. Intracranial hemorrhage (ICH) has been reported in 0.4%–1.3% of cases in clinical trials of the predominantly single-chain agent “alteplase” (Genentech Laboratories, South San Francisco, CA) [8]. An overall rate of 0.68% was derived from the analysis of a combined experience of 5258 patients treated in the United States and European clinical trials of coronary thrombolysis [4].