Studies of snake venoms on blood coagulation I. The thromboserpentin (thrombin-like) enzyme in the venoms

Abstract

Abstract An experimental survey was made on the thrombin-like activity of the venoms from forty-three species of all four groups of snakes. The term “thromboserpentin” is introduced for this activity to differentiate it from other endopeptidases contained in snake venoms. Thromboserpentin activity was estimated by the “fibrin time”, denoting the first macroscopic appearance of fibrin strands, and by the gelation time, denoting the appearance of a gel. Thromboserpentin activity was found in most of the Crotalidae group of venoms. Vipera ammodytes venom was the only one in the Viperidae group with thromboserpentin activity, and none was found in the venoms of the Elapidae and Hydrophidae groups of snakes. Heparin and peanut inhibitor were used to characterize the mode of action of the thromboserpentin enzyme. Heat treatment was employed to eliminate other venom containing proteases which might interfere with the gelation time of the fibrinogen-thromboserpentin systems. Rigid fibrin gels were observed in these systems in the presence of high concentrations of heparin. The heparin action on thromboserpentin-fibrinogen systems is discussed in relation to a heparin-thrombin complex and a heparin-fibrin complex. The possibility of the role of heparin on the gelation phase, in addition to its role as an anticoagulant, is discussed in connection with the findings that the fibrin gels induced by the venoms of Agkistrodon mokeson and Lachesis mutus do not dissolve, but remain firm. A close relationship is proposed to exist between heparin and fibrin gel structure, induced either by thrombin or by thromboserpentin. The presented findings of the action of peanut inhibitor suggest that it inhibits specifically thromboserpentin. The application of thromboserpentin is considered useful for studies on the polymerization, gelation and cross-linking of fibrin.