Effect of heparin administration on fibrinogenolysis during thrombolytic therapy with tissue plasminogen activator for acute myocardial infarction

Heparin accelerates plasminogen activation by tissue type plasminogen activator (t-PA). Previous investigators have postulated that heparin administration during t-PA therapy might lead to enhanced fibrinogenolysis. In this paper, important coagulation parameters from a randomised trial of early versus delayed heparin administration, during t-PA therapy for acute myocardial infarction, were analysed. In contrast to the prediction, the late heparin group had significantly greater fibrinogen depletion (nadir fibrinogen 1.06±0.65 g/1 vs 1.46±0.61 g/l, p=0.0001) and higher fibrinogen degradation products (peak FBDP 675.9±785.3 μg/ml vs 299.7±543.5 μg/ml, p=0.0001). A possible mechanism for these findings is discussed. It has previously been demonstrated that heparin and FBDP are competitive activators of plasminogen activation by t-PA. It has also been shown that the stimulation of plasminogen activation by FBDP contributes substantially to fibrinogenolysis by t-PA. Thus, heparin may reduce fibrinogenolysis by interfering with the stimulation of plasminogen activation by FBDP. © 1993.

Duke Scholars

Author Robert M. Califf Medicine, Cardiology