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Snakebite-Induced Coagulopathy and Bleeding Disorders

  • Ponlapat Rojnuckarin
Chapter

Abstract

Snake venoms target mainly neuromuscular and/or hemostatic systems. Each of them is a combination of several toxins. Therefore, coagulopathy is only a part of multi-systemic involvement from envenomation including muscular weakness, rhabdomyolysis, renal failure and hypotension. Kinetics studies reveal that viper venoms comprise long half-life components resulting in a delay onset and prolonged duration of bleeding in a subset of patients. On the other hand, elapid venoms are more rapidly cleared from the circulation showing faster recovery. Remarkably, snake venoms affect almost every component of hemostasis including vascular wall, platelets, coagulation factors, natural anticoagulants and fibrinolysis. They can be stimulatory or inhibitory through enzymatic or binding mechanisms. These effects can contribute to hemorrhagic, as well as thrombotic, manifestations of snakebites. The most prominent clinical syndrome is consumptive coagulopathy from the thrombin-like enzymes and/or coagulation factor activators in the venoms. In addition, anticoagulation syndrome, thromboembolism and thrombotic microangiopathy have been reported in victims of particular snake species. The key treatment of snakebites is antivenom that can promptly reverse coagulopathy in most situations.

Keywords

Snake Venom Thrombotic Microangiopathy Venom Component Consumptive Coagulopathy Brown Snake 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Aragon-Ortiz, F., Gubensek, F., 1993. A thrombin-like enzyme from bushmaster (Lachesis muta stenophyrs) venom. Toxicon 31, 1435–1443.PubMedCrossRefGoogle Scholar
  2. Chotenimitkhun, R., Rojnuckarin, P., 2008. Systemic antivenom and skin necrosis after green pit viper bites. Clin. Toxicol. 46, 122–125.CrossRefGoogle Scholar
  3. Date, A., Pulimood, R., Jacob, C.K., Kirubakaran, M.G., Shastry, J.C., 1986. Haemolytic-uraemic syndrome complicating snake bite. Nephron 42, 89–90.PubMedCrossRefGoogle Scholar
  4. Flight, S.M., Johnson, L.A., Du, Q.S., Warner, R.L., Trabi, M., Gaffney, P.J., Lavin, M.F., de Jersey, J., Masci, P.P., 2009. Textilinin-1, an alternative anti-bleeding agent to aprotinin: importance of plasmin inhibition in controlling blood loss. Br. J. Haematol. 145, 207–211.PubMedCrossRefGoogle Scholar
  5. Gold, B.S., Barish, R.A., Dart, R.C., 2004. North American snake envenomation: diagnosis, treatment, and management. Emerg. Med. Clin. North Am. 22, 423–443.PubMedCrossRefGoogle Scholar
  6. Gomperts, E.D., Demetriou, D., 1977. Laboratory studies and clinical features in a case of boomslang envenomation. S. Afr. Med. J. 51, 173–175.PubMedGoogle Scholar
  7. Gutiérrez, J.M., León, G., Rojas, G., Lomonte, B., Rucavado, A., Chaves, F., 1998. Neutralization of local tissue damage induced by Bothrops asper (terciopelo) snake venom. Toxicon 36, 1529–1538.PubMedCrossRefGoogle Scholar
  8. Gutiérrez, J.M., Rucavado, A., 2000. Snake venom metalloproteinases: their role in the pathogenesis of local tissue damage. Biochimie 82, 841–850.PubMedCrossRefGoogle Scholar
  9. Hutton, R.A., Looareesuwan, S., Ho, M., Silamut, K., Chanthavanich, P., Karbwang, J., Supanaranond, W., Vejcho, S., Viravan, C., Phillips, R.E., Warrell, D.A., 1990. Arboreal green pit vipers (genus Trimeresurus) of South-East Asia: bites by T. albolabris and T. macrops in Thailand and a review of the literature. Trans. Roy. Soc. Trop. Med. Hyg. 84, 866–874.PubMedCrossRefGoogle Scholar
  10. Isbister, G.K., Little, M., Cull, G., McCoubrie, D., Lawton, P., Szabo, F., Kennedy, J., Trethewy, C., Luxton, G., Brown, S.G., Currie, B.J., 2007. Thrombotic microangiopathy from Australian brown snake (Pseudonaja) envenoming. Intern. Med. J. 37, 523–528.PubMedCrossRefGoogle Scholar
  11. Isbister, G.K., 2009. Procoagulant snake toxins: laboratory studies, diagnosis, and understanding snakebite coagulopathy. Semin. Thromb. Hemost. 35, 93–103.PubMedCrossRefGoogle Scholar
  12. Isbister, G.K., Duffull, S.B., Brown, S.G.; ASP Investigators, 2009. Failure of antivenom to improve recovery in Australian snakebite coagulopathy. Q. J. Med. 102, 563–568.CrossRefGoogle Scholar
  13. Kanjanabuch, T., Sitprija, V., 2008. Snakebite nephrotoxicity in Asia. Semin. Nephrol. 28, 363–372.PubMedCrossRefGoogle Scholar
  14. Keyler, D.E., 2008. Envenomation by the lowland viper (Proatheris superciliaris): severe case profile documentation. Toxicon 52, 836–841.PubMedCrossRefGoogle Scholar
  15. Kini, R.M., 2005. Structure-function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms. Toxicon 45, 1147–1161.PubMedCrossRefGoogle Scholar
  16. Lakier, J.B., Fritz, V.U., 1969. Consumptive coagulopathy caused by a boomslang bite. S. Afr. Med. J. 43, 1052–1055.PubMedGoogle Scholar
  17. Lee, W.H., Zhang, Y., Wang, W.Y., Xiong, Y.L., Gao, R., 1995. Isolation and properties of a blood coagulation factor X activator from the venom of king cobra (Ophiophagus hannah). Toxicon 33, 1263–1276.PubMedCrossRefGoogle Scholar
  18. Li, Q.B., Huang, G.W., Kinjoh, K., Nakamura, M., Kosugi, T., 2001. Hematological studies on DIC-like findings observed in patients with snakebite in south China. Toxicon 39, 943–948.PubMedCrossRefGoogle Scholar
  19. Mahasandana, S., Rungruxsirivorn, Y., Chantarangkul, V., 1980. Clinical manifestations of bleeding following Russell’s viper and Green pit viper bites in adults. Southeast Asian J. Trop. Med. Public Health. 11, 285–293.PubMedGoogle Scholar
  20. Mitrakul, C., 1979. Effect of five Thai snake venoms on coagulation, fibrinolysis and platelet aggregation. Southeast Asian J. Trop. Med. Public Health. 10, 266–275.PubMedGoogle Scholar
  21. Mitrakul, C. Juzi, U, Pongrujikorn, W., 1991. Antivenom therapy in Russell’s viper bite. Am J Clin. Pathol. 95, 412–417.PubMedGoogle Scholar
  22. Muanpasitporn, C., Rojnuckarin, P., 2007. Expression and characterization of a recombinant fibrinogenolytic serine protease from green pit viper (Trimeresurus albolabris) venom. Toxicon 49, 1083–1089.PubMedCrossRefGoogle Scholar
  23. Numeric, P., Moravie, V., Didier, M., Chatot-Henry, D., Cirille, S., Bucher, B., Thomas, L., 2002. Multiple cerebral infarctions following a snakebite by Bothrops caribbaeus. Am. J. Trop. Med. Hyg. 67, 287–288.PubMedGoogle Scholar
  24. Otero-Patiño, R., Cardoso, J.L., Higashi, H.G., Nunez, V., Diaz, A., Toro, M.F., Garcia, M.E., Sierra, A., Garcia, L.F., Moreno, A.M., Medina, M.C., Castañeda, N., Silva-Diaz, J.F., Murcia, M., Cardenas, S.Y., Dias da Silva, W.D., 1998. A randomized, blinded, comparative trial of one pepsin-digested and two whole IgG antivenoms for Bothrops snake bites in Uraba, Colombia. The regional group on antivenom therapy research (REGATHER). Am. J. Trop. Med. Hyg. 58, 183–189.PubMedGoogle Scholar
  25. Pinho, F.M., Yu, L., Burdmann, E.A., 2008. Snakebite-induced acute kidney injury in Latin America. Semin. Nephrol. 28, 354–362.PubMedCrossRefGoogle Scholar
  26. Reid, H.A., Chan, K.E., Thean, P.C., 1963. Prolonged coagulation defect (defibrination syndrome) in Malayan viper bite. Lancet 1, 621–626.PubMedCrossRefGoogle Scholar
  27. Rojnuckarin, P., Mahasandana, S., Intragumthornchai, T., Sutcharitchan, P., Swasdikul, D., 1998. Prognostic factors of green pit viper bites. Am. J. Trop. Med. Hyg. 58, 22–25.PubMedGoogle Scholar
  28. Rojnuckarin, P., Intragumtornchai, T., Sattapiboon, R., Muanpasitporn, C., Pakmanee, N., Khow, O., Swasdikul, D., 1999. The effects of green pit viper (Trimeresurus albolabris and Trimeresurus macrops) venom on the fibrinolytic system in human. Toxicon 37, 743–755.PubMedCrossRefGoogle Scholar
  29. Rojnuckarin, P., Chanthawibun, W., Noiphrom, J., Pakmanee, N., Intragumtornchai, T., 2006. A randomized, double-blind, placebo-controlled trial of antivenom for local effects of green pit viper bites. Trans. Roy. Soc. Trop. Med. Hyg. 100, 879–884.PubMedCrossRefGoogle Scholar
  30. Rojnuckarin, P., Banjongkit, S., Chantawibun, W., Akkawat, B., Juntiang, J., Noiphrom, J., Pakmanee, N., Intragumtornchai, T., 2007. Green pit viper (Trimeresurus albolabris and T. macrops) venom antigenaemia and kinetics in humans. Trop. Doct. 37, 207–210.PubMedCrossRefGoogle Scholar
  31. Sano-Martins, I.S., Fan, H.W., Castro, S.C., Tomy, S.C., Franca, F.O., Jorge, M.T., Kamiguti, A.S., Warrell, D.A., Theakston, R.D., 1994. Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Butantan Institute Antivenom Study Group. Toxicon 32, 1045–1050.PubMedCrossRefGoogle Scholar
  32. Schneemann, M., Cathomas, R., Laidlaw, S.T., El Nahas, A.M., Theakston, R.D., Warrell, D.A., 2004. Life-threatening envenoming by the Saharan horned viper (Cerastes cerastes) causing micro-angiopathic haemolysis, coagulopathy and acute renal failure: clinical cases and review. Q. J. Med. 97, 717–727.CrossRefGoogle Scholar
  33. Sharp, P.J., Berry, S.L., Spence, I., Howden, M.E., 1989. A basic phospholipase A from the venom of the Australian king brown snake (Pseudechis australis) showing diverse activities against membranes. Comp. Biochem. Physiol. B. 92, 501–508.PubMedGoogle Scholar
  34. Tanos, P.P., Isbister, G.K., Lalloo, D.G., Kirkpatrick, C.M., Duffull, S.B., 2008. A model for venom-induced consumptive coagulopathy in snake bite. Toxicon 52, 769–780.PubMedCrossRefGoogle Scholar
  35. Than-Than, Hutton, R.A., Myint-Lwin, Khin-Ei-Han, Soe-Soe, Tin-Nu-Swe, Phillips, R.E., Warrell, D.A., 1988. Haemostatic disturbances in patients bitten by Russell’s viper (Vipera russelli siamensis) in Burma. Br. J. Haematol. 69, 513–520.PubMedCrossRefGoogle Scholar
  36. Thiansookon, A., Rojnuckarin, P., 2008. Low incidence of early reactions to horse-derived F(ab’)(2) antivenom for snakebites in Thailand. Acta. Trop. 105, 203–205.PubMedCrossRefGoogle Scholar
  37. Thomas, L., Tyburn, B., Bucher, B., Pecout, F., Ketterle, J., Rieux, D., Smadja, D., Garnier, D., Plumelle, Y., 1995. Prevention of thromboses in human patients with Bothrops lanceolatus envenoming in Martinique: failure of anticoagulants and efficacy of a monospecific antivenom. Research group on snake bites in martinique. Am. J. Trop. Med. Hyg. 52, 419–426.PubMedGoogle Scholar
  38. Thomas, L., Tyburn, B., Ketterlé, J., Biao, T., Mehdaoui, H., Moravie, V., Rouvel, C., Plumelle, Y., Bucher, B., Canonge, D., Marie-Nelly, C.A., Lang, J., 1998. Prognostic significance of clinical grading of patients envenomed by Bothrops lanceolatus in Martinique. Members of the research group on snake bite in martinique. Trans. Roy. Soc. Trop. Med. Hyg. 92, 542–545.PubMedCrossRefGoogle Scholar
  39. Visudhiphan, S., Dumavibhat, B., Trishnananda, M., 1981. Prolonged defibrination syndrome after green pit viper bite with persisting venom activity in patient’s blood. Am. J. Clin. Pathol. 75, 65–69.PubMedGoogle Scholar
  40. Warrell, D.A., 1989. Snake venoms in science and clinical medicine. 1. Russell’s viper: biology, venom and treatment of bites. Trans. Roy. Soc. Trop. Med. Hyg. 83, 732–740.PubMedCrossRefGoogle Scholar
  41. White, J., 1998. Envenoming and antivenom use in Australia. Toxicon 36, 1483–1492.PubMedCrossRefGoogle Scholar
  42. White, J., 2005. Snake venoms and coagulopathy. Toxicon 45, 951–967.PubMedCrossRefGoogle Scholar
  43. Yukelson, L.Y., Tans, G., Thomassen, M.C., Hemker, H.C., Rosing, J., 1991. Procoagulant activities in venoms from central Asian snakes. Toxicon 29, 491–502.PubMedCrossRefGoogle Scholar
  44. Zhang, Y., Xiong, Y.L., Bon, C., 1995. An activator of blood coagulation factor X from the venom of Bungarus fasciatus. Toxicon 33, 1277–1288.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Division of Hematology, Department of MedicineKing Chulalongkorn Memorial Hospital and Chulalongkorn UniversityBangkokThailand

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