Effects of Chinese Snake Venoms on Blood Coagulation, Purified Coagulation Factors and Synthetic Chromogenic Substrates

Abstract.-We examined the action of venoms from common Chinese Crotalidae and Elapidae snakes on blood coagulation mechanisms. Procoagulant effects were observed with venoms from Agkistrodon acutus, Trimeresurus stejnegeri, Ophiophagus luinnah and Bungarus fasciatus, the latter two only in the presence of Ca2+. After treatment with a serine protease inhibitor (phenylmethanesulfonyl fluoride, PMSF), Agkistrodon acutus venom lost its ability to clot purified fibrinogen but retained its capacity to clot human plasma in the absence of Ca2+. An anticoagulant action was obtained with venoms from Trimeresurus mucrosquamatus, Agkistrodon halys and Naja naja atra. This action was abolished after treatment with a specific inhibitor of PLA 2 activity (p-bromophenacyl bromide, BrPBr), revealing a procoagulant action with high concentrations of treated venoms in the cases of Trimeresurus mucrosquamatus and Agkistrodon halys. The effects of these venoms on hemostasis have been further characterized by measuring their phospholipase A 2 activity, their ability to hydrolyze synthetic chromogenic substrates and to activate purified blood coagulation factors (prodirombin, factor X, protein C and plasminogen). These venoms showed an amidolytic activity which was mainly due to serine proteases (90 to 95 % of inhibition with PMSF). Combining the observations obtained with human plasma and purified blood coagulation factors, we concluded Uiat: i) six of the eight tested Chinese venoms {i.e.: Ophiophagus hannah, Bungarus fasciatus