The activation of plasminogen by tissue plasminogen activator is not enhanced by different heparin species as assessed in vitro with a solid-phase fibrin method

The aim of this study was to evaluate the effect of several heparin species (standard heparin, heparin of low molecular weight: IC 831422, heparin of high affinity for antithrombin III: IC 831435, and heparin of low affinity for antithrombin III: IC 831436) on the different steps of the fibrinolytic mechanism i.e., interaction of tissue-type plasminogen activator (t-PA) with plasminogen activator inhibitor-1 (PAI-1), binding of t-PA and plasmin(ogen) to fibrin and activation of plasminogen on the fibrin surface, in the presence of plasma proteins and factors that modulate fibrinolysis. Fibrinolytic and plasmin amidolytic activities were measured in the presence and absence of heparin. The spectrophotometric assays were performed in the presence and absence of solid-phase fibrin using selective chromogenic substrates for plasmin and saturating concentrations of plasminogen.The overall fibrinolytic activity, the amidolytic activity of mixtures of t-PA or urokinase with plasminogen in the absence of fibrin, the binding of t-PA and plasmin(ogen) to fibrin and the t-PA/PAI-1 interaction were not modified by heparin. In contrast, the activation of plasminogen by fibrin-bound t-PA decreased as a function of the concentration of heparin. Although this effect was not significant at concentrations usually used in routine heparin therapy (0.1 to 1 iu/ml) it might have some relevance when heparin is injected in bolus doses.In conclusion, by using a solid-phase fibrin method which allows the analysis of t-PA/PAI-1 balance, data were obtained indicating that the heparin species tested here neither competed with fibrin for the binding of t-PA, nor potentiated the activation of plasminogen at the fibrin surface.