Snake venom and hemostasis

Abstract

Venomous snakebites are a common cause of death globally. Snake venom main targets are neuromuscular and/or hemostatic systems resulting in paralysis and/or bleeding disorders. This review focuses only on the latter effect. Hemostasis is a complex process keeping the balance between bleeding and thrombosis. Venom genes evolved from a few nontoxic genes, duplicated and recruited to express in venom glands. Subsequently, they undergo accelerated evolution to greatly diversify their toxicity affecting all aspects of hemostasis, including vessel walls, platelets, blood coagulation, natural anticoagulants, and fibrinolysis. The effects can be activating and/or inhibitory. The major classes of venom proteins affecting hemostasis are reviewed. They include viper venom proteins: snake venom serine proteases, snake venom metalloproteinases, disintegrins, snaclecs, and type II phospholipases A 2, as well as elapid proteins: three-finger toxins, prothrombin activators, Kunitztype serine protease inhibitor, and type I phospholipases A 2. Moreover, L-amino acid oxidases and nucleotidases are present in both snake families. Although some of these toxins have no clinical significance, they are currently used or potentially useful as diagnostic or therapeutic agents. From the clinical standpoint, the most common hemostatic defect caused by snakebites is consumptive coagulopathy from venom components that activate the common pathway of blood coagulation: factors X and V, prothrombin, or fibrinogen. This combined with fibrino(geno)lysis, platelet activation, and vessel wall damages results in hypofibrinogenemia, thrombocytopenia, and bleeding. Whole blood clotting time is recommended for diagnosis and follow-up for consumptive coagulopathy after snakebites. Additionally, snakebite-induced anticoagulation syndrome without consumption, thrombotic microangiopathy, and thromboembolism has been occasionally reported.