Inhibitory Effects of Lysine Analogues on t-PA Induced Whole Blood Clot Lysis

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). Howe...

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Bibliographic Details
Main Authors: Krishnamurti, Chitra, Vukelja, Svetislava J, Alving, Barbara M
Format: Report
Language:English
Subjects:
ACIDS
ACTIVATION
AMINO ACIDS
Anatomy and Physiology
BLOOD
BLOOD COAGULATION
BLOOD DISEASES
BLOOD PLASMA
CARBOXYLIC ACIDS
CYCLOHEXANES
EACA(EPSILON AMINOCAPROIC ACID)
ENZYME PRECURSORS
FIBRIN
FIBRINOGEN
HEMORRHAGE
INHIBITION
LYSIS
PATIENTS
RATES
REPRINTS
THROMBOCYTOPENIA
TISSUES(BIOLOGY)
VOLUNTEERS
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Summary: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. Pub. in Thrombosis Research, v73 n6 p419-430, 1994.