Principles Underlying the Use of Conjunctive Agents with Plasminogen Activators

Pharmacological thrombolysis is a dynamic situation in which fibrin degradation occurs concomitant to procoagulant activity. The consequences of enhanced procoagulant and platelet activity may delay or prevent thrombolysis or lead to reocclusive events following successful recanalization. Although heparin and aspirin may attenuate ongoing thrombin and thromboxane generation, respectively, a relatively high percentage (10-20%) of patients treated with heparin and aspirin still have complications associated with thrombolysis. This suggests that heparin and aspirin are not universally effective as the heparin-antithrombin III complex may be inaccessible to fibrin-bound thrombin in the microenvironment of the thrombus and aspirin eliminates only thromboxane-dependent platelet aggregation. Therefore, careful consideration must be given to small molecule, active-site thrombin inhibitors which may prove to be more effective than heparin and to fibrinogen receptor antagonists which block aggregation to all known platelet agonists and have a much broader spectrum of activity than aspirin. Hopefully, well-designed clinical trials will be conducted with safe and effective thrombin inhibitors and/or fibrinogen receptor antagonists in thrombolysis and compared to heparin and aspirin such that potentially the overall efficiency of thrombolysis can be improved upon.