Interactions of Venoms and Venom Components with Blood Platelets

Many venoms demonstrate their main toxicity on systems other than blood. Despite this, many venoms also have effects on blood and blood components such as platelets. Crude venoms of snakes, scorpions and spiders have been shown to have indirect (through stimulation of coagulation or epinephrine release, e.g., Echis carinatus and Gentruroides sculpturatus venoms, respectively) and/or direct effects on platelets. For coagulation-dependent effects on platelets, thrombin- or prothrombin-like action (Agkistrodon rhodostoma or contortrix, Bothrops atrox, Crotalus species) may not affect platelets, while those acting at earlier steps may yield normal thrombin and thus activate platelets (Vipera russelli, Echis carinatus). Crude venom effects can be stimulatory (promote or cause aggregation) or inhibitory, with either predominating as a function of dose. Such variability, if observed, often indicates the presence of opposing activities in crude venom, but may also indicate biphasic activity of a single component (e.g., phospholipase A2). Fractionation of crude venoms of several snakes, particularly pit vipers, has yielded compounds with direct platelet stimulation activity: e.g., aggregoserpentin (Trimeresurus mucrosquamatus), convulxin (Crotalus durissus), crotalocytin (Crotalus horridus horridus) and thrombocytin (Bothrops atrox). These stimulators are polypeptides or glycoproteins, with molecular weights between 35000-80000: one, crotalocytin, is a serine protease. A direct-acting inhibitor has been isolated from Agkistrodon halys venom. Direct aggregatory activity has also been found in a fraction of Loxoscleles reclusa spider venom, specifically in the fraction representing sphingomyelinase D. Centruroides sculpturatus scorpion venom and one fraction of it may induce a low level aggregation which can proceed rapidly to a maximal response on additional stimulation. Since platelets can facilitate coagulation, effects of venoms on platelets may explain in part the ability of the venoms to induce thrombosis and consumption coagulopathies such as disseminated intravascular coagulation. Venoms, and particularly their active fractions, provide unique additional tools for platelet and coagulation research.