Clinical Trial of Epsilon-aminocaproic Acid in Severe Haemophilia.

a naturally occurring plasma globulin, is converted by activators to plasmin, an enzyme which can digest many proteins, including fibrinogen and fibrin, prothrombin, factor V, and antihaemophilic globulin. Under physiological circumstances it is thought that natural inhibitors in the plasma restrict plasmin to digestion of fibrin, but in pathological fibrinolytic (hyperplasminaemic) states plasma proteins, including fibrinogen and antihaemophilic globulin, are digested. Activators of plasminogen include a plasma activator, trace quantities of which are probably responsible for physiological fibrinolytic activity, a urinary activator named urokinase, and activators of bacterial origin-for example, streptokinase. E.A.C.A., a potent competitive inhibitor of plasminogen activation (Alkiaersig et al., 1959), was first used in man by Sherry et al. (1959), who found it effective in inhibiting plasma fibrinolytic activity induced by a variety of plasminogen activators. The value of E.A.C.A. in the treatment of pathological fibrinolytic states has recently been reviewed by McNicol and Douglas (1964), who also discuss the pharmacology and toxicity of E.A.C.A. E.A.C.A., a synthetic amino-acid which closely resembles lysine in structure, is rapidly absorbed when taken by mouth. Peak plasma levels are found about two hours after a single oral dose. Urinary excretion is also rapid, the greater part of a single dose being recovered unchanged in the urine in 12 hours. The action of E.A.C.A. as an inhibitor of plasminogen activation is seen with plasma concentrations above