Snakebite Doesn't Cause Disseminated Intravascular Coagulation: Coagulopathy and Thrombotic Microangiopathy in Snake Envenoming

 

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ABSTRACT

The most common coagulopathy associated with snake envenoming worldwide is venom-induced consumption coagulopathy (VICC), which results from activation of the coagulation pathway by snake toxins including thrombin-like enzymes, prothrombin activators, and factor X activators. VICC has often been likened to disseminated intravascular coagulation (DIC) because of the elevated D-dimer, prolonged prothrombin time, and low fibrinogen. However, VICC is not characterized by other important features of DIC, such as evidence of systemic microthrombi and end-organ failure. In addition, the time course of VICC differs with rapid onset and resolution, and the mechanism of initiation of coagulation activation differs because thrombin generation in DIC is mediated by the tissue factor/factor VIIa pathway. In a proportion of patients with VICC, a clinical syndrome consistent with thrombotic microangiopathy has been reported and is characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. This thrombotic microangiopathy appears to only occur in conjunction with VICC but in several different snakes worldwide including vipers and elapids. Consistent with thrombotic microangiopathy, it progresses despite the resolution of the coagulopathy, suggesting a distinct but related process. The existence of the overlapping clinical syndromes of VICC and thrombotic microangiopathy in snake envenoming is the likely reason for the mistaken idea that snakebite causes DIC.

REFERENCES

• 1 Isbister G K, Currie B J, Little M, Daly F F, Isbister J P. Coagulopathy from tiger snake envenoming and its treatment.  Pathology. 2002;  34 588-590
  CrossrefPubMedGoogle Scholar
• 2 Damus P S, Salzman E W. Disseminated intravascular coagulation.  Arch Surg. 1972;  104 262-265
  PubMedGoogle Scholar
• 3 Levi M. Disseminated intravascular coagulation.  Crit Care Med. 2007;  35 2191-2195
  CrossrefPubMedGoogle Scholar
• 4 Warrell D A, Pope H M, Prentice C R. Disseminated intravascular coagulation caused by the carpet viper (Echis carinatus): trial of heparin.  Br J Haematol. 1976;  33 335-342
  CrossrefPubMedGoogle Scholar
• 5 Masci P P, Rowe E A, Whitaker A N, de Jersey J. Fibrinolysis as a feature of disseminated intravascular coagulation (DIC) after Pseudonaja textilis textilis envenomation.  Thromb Res. 1990;  59 859-870
  CrossrefPubMedGoogle Scholar
• 6 Lifshitz M, Kapelushnik J, Ben Harosh M, Sofer S. Disseminated intravascular coagulation after Cerastes vipera envenomation in a 3-year-old child: a case report.  Toxicon. 2000;  38 1593-1598
  CrossrefPubMedGoogle Scholar
• 7 Miao Y N, Chen M C, Huang Z. Clinical observation on treatment of snake bite induced disseminated intravascular coagulation by qinwen baidu decoction [in Chinese].  Zhongguo Zhong Xi Yi Jie He Za Zhi. 2003;  23 590-592
  PubMedGoogle Scholar
• 8 Tin Na Swe, Myint Lwin, Khin Ei Han, Tin Tun, Tun Pe. Heparin therapy in Russell's viper bite victims with disseminated intravascular coagulation: a controlled trial.  Southeast Asian J Trop Med Public Health. 1992;  23 282-287
  PubMedGoogle Scholar
• 9 Taylor Jr F B, Toh C H, Hoots W K, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation.  Thromb Haemost. 2001;  86 1327-1330
  Article in Thieme ConnectPubMedGoogle Scholar
• 10 Isbister G K. Procoagulant snake toxins: laboratory studies, diagnosis, and understanding snakebite coagulopathy.  Semin Thromb Hemost. 2009;  35 93-103
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Swenson S, Markland Jr F S. Snake venom fibrin(ogen)olytic enzymes.  Toxicon. 2005;  45 1021-1039
  CrossrefPubMedGoogle Scholar
• 12 Warrell D A, Davidson N M, Greenwood B M et al.. Poisoning by bites of the saw-scaled or carpet viper (Echis carinatus) in Nigeria.  Q J Med. 1977;  46 33-62
  PubMedGoogle Scholar
• 13 Lalloo D G, Trevett A J, Owens D et al.. Coagulopathy following bites by the Papuan taipan (Oxyuranus scutellatus canni).  Blood Coagul Fibrinolysis. 1995;  6 65-72
  CrossrefPubMedGoogle Scholar
• 14 Tans G, Rosing J. Snake venom activators of factor X: an overview.  Haemostasis. 2001;  31 225-233
  PubMedGoogle Scholar
• 15 Sano-Martins I S, Tomy S C, Campolina D et al.. Coagulopathy following lethal and non-lethal envenoming of humans by the South American rattlesnake (Crotalus durissus) in Brazil.  QJM. 2001;  94 551-559
  CrossrefPubMedGoogle Scholar
• 16 Morling A C, Marshall L R, Herrmann R P. Thrombocytopenia after brown snake envenomation.  Med J Aust. 1989;  151 627-628
  PubMedGoogle Scholar
• 17 Offerman S R, Barry J D, Schneir A, Clark R F. Biphasic rattlesnake venom-induced thrombocytopenia.  J Emerg Med. 2003;  24 289-293
  CrossrefPubMedGoogle Scholar
• 18 Isbister G K, Duffull S B, Brown S G. Failure of antivenom to improve recovery in Australian snakebite coagulopathy.  QJM. 2009;  102 563-568
  CrossrefPubMedGoogle Scholar
• 19 Levi M. Current understanding of disseminated intravascular coagulation.  Br J Haematol. 2004;  124 567-576
  CrossrefPubMedGoogle Scholar
• 20 Levi M, van der Poll T, ten Cate H. Tissue factor in infection and severe inflammation.  Semin Thromb Hemost. 2006;  32 33-39
  Article in Thieme ConnectPubMedGoogle Scholar
• 21 Isbister G K, Scorgie F, Brown S GA, O'Leary M A, Seldon M, Lincz L. Coagulation factor deficiencies associated with venom induced consumption coagulopathy in Australian snake envenoming [abstract].  Clin Toxicol. 2009;  47 462
  PubMedGoogle Scholar
• 22 Isbister G K, Little M, Cull G et al.. Thrombotic microangiopathy from Australian brown snake (Pseudonaja) envenoming.  Intern Med J. 2007;  37 523-528
  CrossrefPubMedGoogle Scholar
• 23 Chugh K S, Aikat B K, Sharma B K, Dash S C, Mathew M T, Das K C. Acute renal failure following snakebite.  Am J Trop Med Hyg. 1975;  24 692-697
  PubMedGoogle Scholar
• 24 Varagunam T, Panabokke R G. Bilateral cortical necrosis of the kidneys following snakebite.  Postgrad Med J. 1970;  46 449-451
  CrossrefPubMedGoogle Scholar
• 25 Harris A R, Hurst P E, Saker B M. Renal failure after snake bite.  Med J Aust. 1976;  2 409-411
  PubMedGoogle Scholar
• 26 Chugh K S, Pal Y, Chakravarty R N et al.. Acute renal failure following poisonous snakebite.  Am J Kidney Dis. 1984;  4 30-38
  PubMedGoogle Scholar
• 27 Schneemann M, Cathomas R, Laidlaw S T, El Nahas A M, Theakston R D, Warrell D A. Life-threatening envenoming by the Saharan horned viper (Cerastes cerastes) causing micro-angiopathic haemolysis, coagulopathy and acute renal failure: clinical cases and review.  QJM. 2004;  97 717-727
  CrossrefPubMedGoogle Scholar
• 28 Cobcroft R G, Williams A, Cook D, Williams D J, Masci P. Hemolytic uremic syndrome following taipan envenomation with response to plasmapheresis.  Pathology. 1997;  29 399-402
  CrossrefPubMedGoogle Scholar
• 29 Fakhouri F, Fremeaux-Bacchi V. Does hemolytic uremic syndrome differ from thrombotic thrombocytopenic purpura?.  Nat Clin Pract Nephrol. 2007;  3 679-687
  CrossrefPubMedGoogle Scholar
• 30 Keyler D E. Envenomation by the lowland viper (Proatheris superciliaris): severe case profile documentation.  Toxicon. 2008;  52 836-841
  CrossrefPubMedGoogle Scholar
• 31 Forzley B R, Clark W F. TTP/HUS and prognosis: the syndrome and the disease(s).  Kidney Int Suppl. 2009;  (112) S59-S61
  CrossrefPubMedGoogle Scholar
• 32 Caprioli J, Noris M, Brioschi S et al.. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome.  Blood. 2006;  108 1267-1279
  CrossrefPubMedGoogle Scholar
• 33 Kruk C, Sprivulis P, Jelinek G A. Two cases of acute renal failure after brown snake bite.  Emerg Med. 1994;  6 17-20
  PubMedGoogle Scholar
• 34 Acott C J. Acute renal failure after envenomation by the common brown snake.  Med J Aust. 1988;  149 709-710
  PubMedGoogle Scholar
• 35 White J, Fassett R. Acute renal failure and coagulopathy after snakebite.  Med J Aust. 1983;  2 142-143
  PubMedGoogle Scholar
• 36 Schapel G J, Utley D, Wilson G C. Envenomation by the Australian common brown snake—Pseudonaja (Demansia) textilis textilis .  Med J Aust. 1971;  1 142-144
  PubMedGoogle Scholar
• 37 Buckley N, Dawson A H. Unusual results of brown snake envenomation.  Med J Aust. 1986;  158 866
  PubMedGoogle Scholar
• 38 Date A, Pulimood R, Jacob C K, Kirubakaran M G, Shastry J C. Haemolytic-uraemic syndrome complicating snake bite.  Nephron. 1986;  42 89-90
  CrossrefPubMedGoogle Scholar
• 39 Warrell D A, Ormerod L D, Davidson N M. Bites by puff-adder (Bitis arietans) in Nigeria, and value of antivenom.  BMJ. 1975;  4 697-700
  CrossrefPubMedGoogle Scholar
• 40 Porath A, Gilon D, Schulchynska-Castel H, Shalev O, Keynan A, Benbassat J. Risk indicators after envenomation in humans by Echis coloratus (mid-east saw scaled viper).  Toxicon. 1992;  30 25-32
  CrossrefPubMedGoogle Scholar
• 41 Gomez H F, Dart R C. Clinical toxicology of snakebite in North America. In: Clinical Toxicology of Animal Venoms and Poisons. 1st ed. Boca Raton, FL; CRC Press 1995: 619-644
  PubMedGoogle Scholar
• 42 Gutierrez J M. Clinical toxicology of snakebite in Central America. In: Clinical Toxicology of Animal Venoms and Poisons. 1st ed Boca Raton, FL; CRC Press 1995: 645-665
  PubMedGoogle Scholar
• 43 Fan H W, Cardoso J L. Clinical toxicology of snake bites in South America. In: Clinical Toxicology of Animal Venoms and Poisons. 1st ed Boca Raton, FL; CRC Press 1995: 667-668
  PubMedGoogle Scholar
• 44 Otero-Patiño R. Epidemiological, clinical and therapeutic aspects of Bothrops asper bites.  Toxicon. 2009;  54 998-1011
  CrossrefPubMedGoogle Scholar
• 45 Isbister G K, Williams V, Brown S G, White J, Currie B J. Clinically applicable laboratory end-points for treating snakebite coagulopathy.  Pathology. 2006;  38 568-572
  CrossrefPubMedGoogle Scholar
• 46 de Silva A, Wijekoon A S, Jayasena L et al.. Haemostatic dysfunction and acute renal failure following envenoming by Merrem's hump-nosed viper (Hypnale hypnale) in Sri Lanka: first authenticated case.  Trans R Soc Trop Med Hyg. 1994;  88 209-212
  CrossrefPubMedGoogle Scholar

Geoff IsbisterM.D. 

Department of Clinical Toxicology, Calvary Mater Newcastle Hospital

Edith St, Waratah NSW 2298, Australia

Email: geoffrey.isbister@newcastle.edu.au