Rattlesnake Venom Enzymes that Interact with Components of the Hemostatic System

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Abstract
Venom from snakes of the genus Crotalus (rattlesnakes) contain several enzymes that interact with platelets or proteins of the blood coagulation system. Although recognized experimentally by their effect on components of the hemostatic system, it should be noted that these venom enzymes are proteinases and their specificities may not be uniquely directed to the clotting proteins or platelets. There are primarily three different activities in rattlesnake venoms that account for interactions of the venoms with blood-borne components of the hemostatic system; thrombin-like, platelet aggregating, and fibrin(ogen)olytic. Although these activities are present in many rattlesnake venoms, they are not always present simultaneously in venom from every species. Thrombin-like enzymes are serine esterases that have been described in a variety of rattlesnake venoms and have been purified from several of them. These enzymes produce a benign state of defibrinogenation following intravenous infusion. They have little or no direct fibrinolytic action. The enzyme from eastern diamondback rattlesnake venom has recently been shown to possess certain structural and enzymatic activities similar to kallikrein. Fibrin(ogen)olytic enzymes have been reported in many different rattlesnake venoms. Recent interest has been focused on these enzymes in view of their clinical potential as thrombolytic agents. Platelet active enzymes have been described by several investigators in different rattlesnake venoms and a proteolytic enzyme has been purified from timber rattlesnake venom that causes platelet aggregation and nucleotide release. Separate studies have revealed that specific rattlesnake venom metallopro-teinases inactivate plasma antiproteinases such as antithrombin III and α1 antiproteinase. The action of these metalloproteinases could reinforce the hemostatic interactions of other venom enzymes by inactivating inhibitors of activated clotting factors generated by these venom enzymes. There is an isolated report of a factor X activating activity in a rattlesnake venom.