T H E Coagulation of Blood by Snake Venoms and Its Physiologic Significance by Harry

It has recently been demonstrated (5 a) that certain proteolyfic enzymes can cause the coagulation of blood or plasma by either of two mechanisms. Trypsin acts on prothrombin to form thrombin, and is thus the counterpart of the physiologic calcium-platelet system. Papain, however, acts directly on fibrinogen to form a fibrillar gel resembling fibrin, and is thus the counterpart of thrombin. In view of these findings, it was suggested that a calcium-platelet mixture (or a calcium-tissue extract mixture) contains a proteolytie enzyme which, like trypsin, reacts with prothrombin to form thrombin. It was further suggested that thrombin itself is a proteolytic enzyme analogous to papain which hydrolyzes fibrinogen to form an insoluble split product, fibrin. The kinetics of thrombin formation and of the resultant coagulation were found to be in accord with the thesis that physiological coagulation involves these two consecutive enzyme reactions (3, 4). Moreover, an analogy for this hypothesis was seen in the activation of chymotrypsinogen by trypsin to form a new enzyme, chymotrypsin (11). Snake venoms are known to affect the phenomenon of blood coag-ulation profoundly. Some inhibit the clotting process when added to blood in vivo or in vitro, a few have no significant effect, and a large number have a marked coagulative action on whole blood, plasma, or fibrinogen. Most of those who have concerned themselves with the mechanism of this coagulation (1, 6, 9, 10, 13, 14, 21) have found the venoms to act directly on fibrinogen. Only in an early paper by Mel-lanby (15) does one find the suggestion that some other process may be involved. On adding the venom of either Echis carinata (Indian 613