Snake venoms and the hemostatic system

• Published in: Toxicon 1998-12, Vol.36 (12), p.1749-1800
• Main Author: Markland, Francis S.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animal poisons toxicology. Antivenoms; Animals; Anticoagulants - pharmacology; Biological and medical sciences; Blood Coagulation - drug effects; Endopeptidases - pharmacology; Fibrinolysis - physiology; Hemostasis - physiology; Humans; Medical sciences; Molecular Sequence Data; Platelet Aggregation - drug effects; Protease Inhibitors - pharmacology; Serpentes; Snake Venoms - pharmacology; Toxicology
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/S0041-0101(98)00126-3

Snake venoms are complex mixtures containing many different biologically active proteins and peptides. A number of these proteins interact with components of the human hemostatic system. This review is focused on those venom constituents which affect the blood coagulation pathway, endothelial cells, and platelets. Only highly purified and well characterized snake venom proteins will be discussed in this review. Hemostatically active components are distributed widely in the venom of many different snake species, particularly from pit viper, viper and elapid venoms. The venom components can be grouped into a number of different categories depending on their hemostatic action. The following groups are discussed in this review: (i) enzymes that clot fibrinogen; (ii) enzymes that degrade fibrin(ogen); (iii) plasminogen activators; (iv) prothrombin activators; (v) factor V activators; (vi) factor X activators; (vii) anticoagulant activities including inhibitors of prothrombinase complex formation, inhibitors of thrombin, phospholipases, and protein C activators; (viii) enzymes with hemorrhagic activity; (ix) enzymes that degrade plasma serine proteinase inhibitors; (x) platelet aggregation inducers including direct acting enzymes, direct acting non-enzymatic components, and agents that require a cofactor; (xi) platelet aggregation inhibitors including: α-fibrinogenases, 5′-nucleotidases, phospholipases, and disintegrins. Although many snake venoms contain a number of hemostatically active components, it is safe to say that no single venom contains all the hemostatically active components described here. Several venom enzymes have been used clinically as anticoagulants and other venom components are being used in pre-clinical research to examine their possible therapeutic potential. The disintegrins are an interesting group of peptides that contain a cell adhesion recognition motif, Arg–Gly–Asp (RGD), in the carboxy-terminal half of their amino acid sequence. These agents act as fibrinogen receptor (integrin GPIIb/IIIa) antagonists. Since this integrin is believed to serve as the final common pathway leading to the formation of platelet–platelet bridges and platelet aggregation, blockage of this integrin leads to inhibition of platelet aggregation regardless of the stimulating agent. Clinical trials suggest that platelet GPIIb/IIIa blockade is an effective therapy for the thrombotic events and restenosis frequently accompanying cardiovascular and cerebrovascular