Inhibitory Effects of Lysine Analogues on t-PA Induced Whole Blood Clot Lysis
WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
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The lysine analogues epsilon-aminocaproic acid EACA and trans-4- aminomethyl cyclohexane, carboxylic acid AMCA are used to prevent excessive bleeding in patients with coagulopathies, such as hemophilia and thrombocytopenia, or in those who have received tissue plasminogen activator t- PA. However, their relative efficacy in inhibiting lysis of clots that have been formed in the presence of exogenous t-PA or that have been formed and then exposed to exogenous t-PA has not been well characterized. The present study utilized blood from normal volunteers and 125 1-fibrinogen in a dilute whole blood clot assay to determine the relative concentrations of lysine analogues required for inhibition of clot lysis induced by exogenous t-PA. AMCA 0.06 mM and EACA 0.6 mM were effective in prolonging clot lysis if 1 whole blood clots were formed and then exposed to a lysine analogue and exogenous t-PA or if 2 whole blood clots were formed in the presence of exogenous t-PA and a lysine analogue. However, their inhibitory effect was markedly reduced if clots were formed in the presence of t-PA and then exposed to either of the lysine analogues. The analogues did not inhibit the initial binding of t-PA to fibrin. They did inhibit binding of plasminogen to fibrin as well as the activation of plasminogen by t-PA in the absence of fibrin. The data suggest that lysine analogues, even at low concentrations, reduce the rate of t-PA induced whole blood clot lysis by several mechanisms. Lysine analogues, Whole blood clot lysis, Tissue plasminogen activator, Fibrin.
- Anatomy and Physiology