Practical applications of snake venom toxins in haemostasis

Snake venom toxins have an established role in the coagulation laboratory for the assay of haemostatic parameters and a potential role for therapeutic treatment of thrombotic disorders. In the laboratory, snake venom thrombin-like enzymes (SVTLEs) are used for the assay of fibrinogen and detection of fibrinogen breakdown products and dysfibrinogenaemias. Importantly, because SVTLEs are not inhibited by heparin, they can be used for assaying antithrombin III and other parameters in samples which contain heparin. Prothrombin activators occur in many snake venoms and these have become established in the assay of prothrombin, in the study of dysprothrombinaemias and in the preparation of meizothrombin and non enzymic forms of prothrombin. Russell's viper (Daboia russelli) venom contains a number of useful compounds including toxins which can be used to assay blood clotting factors V, VII, X, platelet factor 3 and lupus anticoagulants (LA). More recently, activators from the taipan, Australian brown snake and saw-scaled viper have been used to assay LA. Proteins C and S can be measured by means of protac, a fast acting inhibitor from Southern copperhead snake venom and von Willebrand factor can be studied with botrocetin from Bothrops jararaca venom. The disintegrins, a large family of Arg-Gly-Asp (RGD)-containing proteins found in snake venoms, show great potential for the study of platelet glycoprotein receptors, notably, GPIIb/IIIa and Ib, and in the treatment of arterial thrombotic disease. Established SVTLEs used in clinical practice include ancrod and defibrase although success with these agents has been limited. A further group of enzymes under consideration as thrombolytic agents are the fibrinogenases.