The thrombolytic paradox

Thrombolytic drugs do not only stimulate the plasmin system but also induce thrombin activation additionally to the preexisting hypercoagulative state in patients with acute myocardial infarction. Testing the in vitro-derived hypothesis of a plasmin-mediated activation of the contact phase of the co agulation leading to the procoagulant effect, several thrombolytic regimen have been evaluated. Paradoxical thrombin activation (referred to as "throm bolytic paradox") was related to absence of fibrin specificity. Highly fibr in-specific drugs like tenecteplase did not cause additional thrombin activ ation, while non-fibrin-specific drugs like streptokinase caused a marked a dditional activation of the contact phase and of thrombin. It could be show n that the thrombolytic paradox was related to the extent of systemic plasm in activation confirming the hypothesis of a plasmin-mediated factor XII/ka llikrein system activation as cause of the thrombolytic paradox. (C) 2001 E lsevier Science Ltd. All rights reserved.