Evaluation of the inhibition by heparin and hirudin of coagulation activation during r-tPA-induced thrombolysis.
Thrombin bound to a fibrin clot remains active and poorly accessible to heparin-AT III complex. During fibrinolysis, thrombin is released as thrombin-FDP complex and is inactivated by heparin-AT III. However, as successive fibrin layers are removed, inaccessible molecules of thrombin are exposed at the surface of the residual clot, possibly contributing to the occurrence during thrombolytic therapy of coagulation that is poorly controlled by heparin. We have investigated the accessibility of fibrin-bound thrombin to hirudin. The results clearly show that two recombinant hirudin variants neutralize thrombin both in solution and fibrin bound. Furthermore, we have found that in in vitro models, hirudin present in the surrounding medium of a clot under lysis is more efficient than heparin in preventing the activation of coagulation. This observation suggests that hirudin may be effective in the prevention of the rethrombotic process frequently encountered during thrombolytic therapy.
Mirshahi
M
M
Institut des vaisseaux et du sang (IVS), Hopital Lariboisiere, Paris, FRG.
Soria
J
J
Soria
C
C
Faivre
R
R
Lu
H
H
Courtney
M
M
Roitsch
C
C
Tripier
D
D
Caen
J P
JP
D000327:Adsorption; D000990:Antithrombin III / Q000494:pharmacology; D001780:Blood Coagulation Tests; D005337:Fibrin / Q000502:physiology; D005342:Fibrinolysis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D011994:Recombinant Proteins; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D010959:Tissue Plasminogen Activator
D006629:Hirudins; D011994:Recombinant Proteins; D000990:Antithrombin III; D005337:Fibrin; D006493:Heparin; D013917:Thrombin; D010959:Tissue Plasminogen Activator