Thrombin-like snake venom proteinases.

Proteinases affecting one or several physiological thrombin substrates are current components of Crotalidae and Viperidae venoms. Enzymes causing in vitro coagulation of fibrinogen without affecting other thrombin-susceptible blood constituents as well as enzymes affecting platelets, F. V. VIII and XIII with only minor action on fibrinogen have been isolated. Fibrinogen affecting proteinases may catalyze the release of either fibrinopeptide (Fp) A (e.g. ancrod, batroxobin) or Fp B (Agk, contortrix proteinase) or of both Fp A and B (B. gabonica proteinase). Some of these enzymes are inhibited by AT III-heparin complex (e.g. Agk. contortrix proteinase) some are not inhibited by either AT III-heparin or hirudin (e. g. batroxobin). The application of Fp A releasing venom proteinases into animals causes transformation of fibrinogen into fibrin I monomer which is rapidly degraded by fibrinolysis and thereby leads to a state of afibrinogenaemia. The administered enzyme is gradually bound to serum proteinase-inhibitors and inactivated. A species dependent interaction between venom enzyme, fibrinogen and serum proteinase inhibitors creates specific differences in dose response relationship. Thus, batroxobin isolated from B. moojeni (HOGE) proved to be a superior defibrinogenating agent in man, as compared to the closely related enzyme isolated from B. atrox (L.). LD50 of B. atrox venom in previously batroxobin defibrinogenated mice is not significantly different as compared to normal animals, indicating an only minor role of batroxobin in Bothrops venom poisoning.