Mechanism of Clot Lysis

Abstract

THE availability of a large number of inhibitors of proteolytic enzymes, as well as the availability of highly purified streptokinase, plasminogen and plasmin, suggested to me the investigation of the nature of the enzyme or enzymes capable of dissolving fibrin clots. Proteolytic enzymes in general, but more particularly trypsin and chymotrypsin, are known for their ability to digest fibrin clots; certain snake venoms can also do this. The proteolysis of fibrinogen and fibrin by venoms, trypsin or plasmin appears to vary, depending upon which of the enzyme is used. The clotting of fibrinogen is the result of the splitting of an arginine peptide bond in the fibrinogen molecule¹; this tends to produce a product (fibrin) which is much less susceptible to hydrolysis by trypsin and venoms than the parent substance, fibrinogen^2,3. Fibrin, on the other hand, is as sensitive to plasmin as is fibrinogen³.