The Role of Venom Haemorrhagin in Spontaneous Bleeding in Bothrops jararaca Envenoming

Summary

Thirty-eight patients bitten by Bothrops jararaca were investigated. Twenty-six had signs of local or systemic haemorrhage. Twenty-two of these had incoagulable blood, and these patients were found to have low fibrinogen levels (mean 0.17 ± 0.03 g/1), thrombocytopenia, very high thrombin-antithrombin III complex (850 ± 184 pg/1) and D-dimer (170 ± 44 μg/ml) antigen levels. Serum venom haemorrhagin levels were significantly higher in patients with clinical signs of haemorrhage (36.4 ± 6.4 ng/ml) than those without (11.7 ± 3.7 ng/ml; p <0.002). Twelve out of 13 patients with thrombocytopenia were bleeding. High levels of thrombomodulin (22.3 ± 1.5 ng/ml) and haemorrhagin (35.7 ± 7.7 ng/ml) were detected in these 12 patients, suggesting vascular endothelial damage. Haemorrhagin levels also correlated inversely with platelet count in these patients. It was concluded that thrombocytopenia is one of the main causes of bleeding inB. jararaca victims, possibly as a result of venom haemorrhagin activity.

• 1 Kamiguti AS, Matsunaga S, Spir M, Sano-Martins IS, Nahas L. Alteration of the blood coagulation system after accidental human inoculation by Bothrops jararaca venom. Braz J Med Biol Res 1986; 19: 199-204
• 2 Kamiguti AS, Cardoso JLC, Theakston RDG, Sano-Martins IS, Hutton RA, Rugman FP, Warrell DA, Hay CRM. Coagulopathy and haemorrhage in human victims of Bothrops jararaca envenoming in Brazil. Toxicon 1991; 29: 961-972
• 3 Maruyama M, Kamiguti AS, Cardoso JLC, Sano-Martins IS, Chud-zinski AM, Santoro ML, Morena P, Tomy SC, Antonio LC, Mihara H, Kelen EMA. Studies on blood coagulation and fibrinolysis in patients bitten by Bothrops jararaca (jararaca) . Thromb Haemostas 1990; 63: 449-453
• 4 Read MS, Shermer RW, Brinkhous KM. Venom coagglutinin; an activator of platelet aggregation dependent on von Willebrand factor. Proc Natl Acad Sci USA 1978; 75: 4514-4518
• 5 Brinkhous KM, Barnes DS, Potter JY, Read MS. Von Willebrand syndrome induced by a Bothrops venom factor: bioassay for venom coagglutinin. Proc Natl Acad Sci USA 1981; 78: 3230-3234
• 6 Sanders WE, Read MS, Reddick RL, Garris JB, Brinkhous KM. Thrombotic thrombocytopenia with von Willebrand deficiency induced by botrocetin: an animal model. Lab Invest 1988; 59: 443-452
• 7 Mandelbaum FR, Reichl AP, Assakura MT. Some physical and biochemical characteristics of HF2, one of the haemorrhagic factors in the venom of Bothrops jararaca . In: Animal, Plant and Microbial Toxins, Vol. 1. Ohsaka A, Hayashi K, Sawai Y. (eds) Plenum Press; London: 1976. pp 111-121
• 8 Mandelbaum FR, Assakura MT, Reichl AP. Characterization of two hemorrhagic factors isolated from the venom of Bothrops neuwiedi (jararaca pintada) . Toxicon 1984; 22: 193-206
• 9 Rosenfeld G. Symptomatology, pathology and treatment of snake bites in South America. In: Venomous Animals and their Venoms, Vol. 2. Bucherl W, Buckley E, Deulofeu V. (eds) Academic Press; New York: 1971. pp 345-384
• 10 Warrell DA, Davidson NMcD, Greenwood BM, Ormerod LD, Pope HM, Watkins BJ, Prentice CRM. Poisoning by bites of the saw-scaled or carpet viper (Echis carinatus) in Nigeria. Quart J Med 1977; 46: 33-62
• 11 Theakston RDG, Lloyd-Jones MJ, Reid HA. Micro-ELISA for detecting and assaying snake venom and venom antibody. Lancet 1977; ii: 639-641
• 12 Ho M, Warrell MJ, Warrell DA, Bid well D, Voller A. A critical reappraisal of the use of enzyme-linked immunosorbent assays in the study of snake bite. Toxicon 1986; 24: 211-221
• 13 Kamiguti AS, Theakston RDG, Desmond H, Hutton RA. Systemic haemorrhage in rats induced by a haemorrhagic fraction from Bothrops jararaca venom. Toxicon 1991; 29: 1097-1105
• 14 Brecher G, Cronkite EP. Morphology and enumeration of human blood platelets. J Appl Physiol 1950; 3: 365-377
• 15 Ratnoff OD, Menzie C. A new method for the determination of fibrinogen in small samples of plasma. J Lab Clin Med 1951; 37: 316-320
• 16 Ishii H, Nakano M, Tsubouchi J, Ishikawa T, Uchiyama H, Hiraishi S, Tahara C, Miyajima Y, Kazama M. Establishment of enzyme immunoassay of human thrombomodulin in plasma and urine using monoclonal antibodies. Thromb Haemostas 1990; 63: 157-162
• 17 Reid HA. Defibrination by Agkistrodon rhodostoma venom. In: Animal Toxins. Russell FE, Saunders PR. (eds) Pergamon Press; Oxford: 1967. pp 323-325
• 18 Ohsaka A. Hemorrhagic, necrotizing and edema-forming effects of snake venoms. In: Snake Venoms. Lee CY. (ed) Springer; Berlin: 1979. pp 480-546
• 19 Chesterman CN. Vascular endothelium, haemostasis and thrombosis. Blood Rev 1988; 2: 88-94
• 20 Rodgers GM. Haemostatic properties of normal and perturbed vascular cells. FASEB J 1988; 2: 116-123
• 21 Ishii H, Uchiyama H, Kazama M. Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells. Thromb Haemostas 1991; 65: 618-623
• 22 Rugman FP, Kamiguti AS, Ishii H, Theakston RDG, Hay CRM. Plasma thrombomodulin as a marker of endothelial injury in Brazilian Bothrops jararaca envenomation. Br J Haematol 1991; 77: 41