snake bite blood coagulation
100, 879–884. It is typically caused by vipers, such as Russell’s viper (Daboia russelli), saw scale viper (Echis carinatus), South American rattle snake (Crotalus durissus terrificus), bushmaster (Lachesis spp.) Public Health. Isbister, G.K., Duffull, S.B., Brown, S.G.; ASP Investigators, 2009. Structure-function relationships and mechanism of anticoagulant phospholipase A. Lakier, J.B., Fritz, V.U., 1969. Muanpasitporn, C., Rojnuckarin, P., 2007. Trop. ), as well as Russell’s viper (Daboia russelli) particularly in Sri Lanka. WBCT can also be used to assess the effectiveness of antivenom therapy. Clipboard, Search History, and several other advanced features are temporarily unavailable. If left untreated, these could lead to infections. From Wikipedia, the free encyclopedia Whole blood clotting test (WBCT) a blood test used to check the coagulation mechanism in the blood following a snake bite. Advances in antivenom production using caprylic acid to stabilize the IgG molecules and/or cleaving the complement-activating Fc portion of IgG markedly reduced the incidence (Otero-Patiño et al., 1998). The recommended laboratory investigation worldwide is the whole blood clotting time because it is rapid and available everywhere even in remote community hospitals. Toxicon 45, 951–967. Minerva Cardioangiol. North Am. This paper reviews clinical aspects of snakebite coagulopathy, including types of coagulopathy (procoagulant, fibrinogen clotting, fibrinolytic, platelet-active, anticoagulant, thrombotic, haemorrhagic), diagnosis and treatment. ), rattle snakes (Crotalus adamanteus), ii. Soc. J. Sun and Gailani, 1996. The brief summary is shown in Fig. A proportion of venomous snakebite does not show any symptom because the toxins are not injected. [Coagulation disorders caused by snake bite]. [Study of blood coagulation disorders after operations with extracorporeal circulation in infants and children]. These complications can effectively be prevented using the specific antivenom (Thomas et al., 1995). Clin Pharmacol Ther 86: 290–298. Destruction of red blood cells and the inability of blood to clot cause serious internal bleeding. Fresh frozen plasma and/or platelet transfusion is usually ineffective and unnecessary. T he majority of patients presenting to Australian emergency departments with suspected snakebite do not develop envenoming.1-3 The accepted policy in Australia is for patients to be observed and have serial blood samples tested for up to 24 hours after a bite, as well as removal of any first aid such as pressure bandages with immobilisation (PBI). Toxicon 52, 769–780. Therefore, the formed clots are friable and subjected to endogenous and venom-induced fibrinolysis causing defibrination syndrome in humans (Rojnuckarin et al., 1999). Furthermore, many proteolytic enzymes, which may aid prey digestion, can disrupt vascular wall, destroy clotting factors and, thus, significantly contribute to the hemorrhagic diathesis. Subsequently, the body produces clotting factors and platelets to restore normal hemostasis. The 20-minute whole blood clotting test (WBCT20) is used as a bedside diagnostic test for coagulopathic snake envenoming. Prediction of snake bite data2.2.1. Author information: (1)Hospital Ars Veterinaria, Barcelona, Spain. More standardized tests, e.g. Med. Coagulation activators are also implicated in occasional thrombosis after snakebites. Mitrakul, C., 1979. A randomized controlled trial will definitely prove the role of plasma infusion after elapid bites. Thrombotic microangiopathy from Australian brown snake (. Reticulocytes may not be appropriately increased due to impaired kidney functions. Lee, W.H., Zhang, Y., Wang, W.Y., Xiong, Y.L., Gao, R., 1995. Coagulation activation: This is the principal effect of venom in vivo. Toxicon 36, 1483–1492. Blood Coagulation & Fibrinolysis: March 2018 - Volume 29 - Issue 2 - p 196-204. doi: 10.1097/MBC.0000000000000702 . 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. Nephron 42, 89–90. The most prominent clinical syndrome is consumptive coagulopathy from the thrombin-like enzymes and/or coagulation factor activators in the venoms. Effect of five Thai snake venoms on coagulation, fibrinolysis and platelet aggregation. ), Rough scale snake (Tropidechis carinatus), Taipan (Oxyurenus spp. Thin arrows represent a variety of effects of proteins in the C-type lectin-like family. 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. Furthermore, clotting time is more sensitive to hypofibrinogenemia than the conventional PT or APTT. The only requirements are a clean glass tube and a timer. 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. Clinical manifestations of bleeding following Russell’s viper and Green pit viper bites in adults. Aragon-Ortiz, F., Gubensek, F., 1993. Semin. These keywords were added by machine and not by the authors. On the contrary, elapid venoms contain smaller molecular weight protein. Due to the long (over 24 h) half-life of venoms in circulation, the toxins can continuously destroy clotting factors and platelets. Some may cleave both fibrinopeptides (venombin AB), but incompletely. Therefore, multiple doses of this kind of antivenom are required. In human, due to greatly larger blood volume, the fibrinolytic system activation causes coagulation factor as well as platelet consumption and ensuing bleeding disorders. Med. It should be performed as part of the initial workup and serial reassessments on all snakebite patients in the developing world. Severe internal bleeding occurs as a result of blood cells rupturing and then the inability for the blood to clot. These activations may be followed by shedding of GpVI receptor resulting in subsequent inhibition. and Australian copperhead (Austrelaps spp. Bhargava RK, Hakim A, Shah PK, Mathur SB, Ujjwal JS. Polychromasia is not increased due to erythropoietin deficiency from renal failure, Snakes that cause medically important coagulopathy classified according to the clinical syndromes and their mechanism(s) (Aragon-Ortiz and Gubensek, 1993; Gomperts and Demetriou, 1977; Isbister, 2009), i. In this model, fresh frozen plasma infusion was correlated with early reversal of coagulopathy (Isbister et al., 2009). PMID: 3997754 [PubMed - indexed for MEDLINE] MeSH Terms. of Haematology, Hunter Haematology Research Group, Calvary Mater Hospital Newcastle, Waratah, Australia. Observations on blood coagulation after snakebite in dogs and cats. 83, 732–740. or lance-head vipers (Bothrops spp. Snake venoms mainly target the common pathway of coagulation including factor X, V and prothrombin activators resulting in consumptive coagulopathy. Hyg. Prevention of thromboses in human patients with, 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. Blood smear examination is helpful for diagnosis of thrombotic microangiopathy (see below). Arrow heads denote the anticoagulant effects of activated protein C (APC) that digests factor Va and VIIIa. Rojnuckarin, P., Mahasandana, S., Intragumthornchai, T., Sutcharitchan, P., Swasdikul, D., 1998. Hypotension and shock are the consequences of several factors including vasodilatory venom proteins, fluid leakage, allergic reactions, toxic myocardial damage and/or bleeding. Gutiérrez, J.M., Rucavado, A., 2000. 1977 Apr;25(4):279-88. Q. J. Med. For example, coagulation factor activators and anticoagulant activities have been discovered in biochemical studies on king cobra (Lee et al., 1995), cobra (Kini, 2005; Yukelson et al., 1991) and krait (Mitrakul, 1979; Zhang et al., 1995) venoms. HOLLOWAY *Department of Veterinary Clinic and Hospital, University of Melbourne, Werribee, Victoria 3030. This may result in very rapid absorption. A serine protease from Agkistrodon concortrix, ACC-C, activates protein C which in turn inactivates factor Va and VIIIa. 1976 Oct;24(10):671-5. Trop. Med. Y. True vipers: Russell’s viper (Daboia russelli), Horned vipers (Cerastes spp. Toxicol. The clinical significance of the differentiation of this syndrome from the consumption is to aid identifying these snake species (Table 39.1). Procoagulant snake toxins: laboratory studies, diagnosis, and understanding snakebite coagulopathy. Public Health. The following blood tests are useful: Coagulation profile (INR, aPTT), fibrinogen and D-dimer or fibrinogen-degradation products (FDPs) May show a venom-induced consumptive coagulopathy (VICC) characterized by: Some also trigger endothelial cell apoptosis. To add more complexity, one species of venom contains several toxins, which may both stimulate and inhibit several or even the same molecular or cellular targets. Li, Q.B., Huang, G.W., Kinjoh, K., Nakamura, M., Kosugi, T., 2001. Nephrol. S. Afr. DESIGN: Prospective observational study. Yukelson, L.Y., Tans, G., Thomassen, M.C., Hemker, H.C., Rosing, J., 1991. The summary of snake venoms affecting hemostasis. Besides hematological disorders, other cardinal features of systemic effects are listed below. A snakebite victim may have minimal symptoms or signs yet still have a potentially life-threatening condition. Centrum voor Wiskunde en Informatica, Amsterdam (1997) pp. The majority of dangerous Australian snakes cause a procoagulant coagulopathy. clear insight into the effect of snake venoms on blood coagulation (Hiremath et al., 2013). These data are consistent with studies in animal models indicating that antivenom is ineffective for local tissue damages by viper venoms (Gutiérrez et al., 1998) and other treatment modalities are required. Fibrinogen is the sole factor consumed by thrombin-like enzymes, while factor X and V levels are depressed by factor X and V activators in Russell’s viper envenomation (Mahasandana et al., 1980). J Assoc Physicians India. This process is experimental and the keywords may be updated as the learning algorithm improves. Watch what happens when one drop of Russell's Viper venom is mixed with a vial of human blood. There is no difference in recovery (INR less than 2.0) rates between cases receiving early vs. late antivenom. The presence of other organ involvement may be helpful in identifying snake species when combined with the data on geographical areas of bites. The local tissue injury may yield pain, limb swelling, cutaneous bullae, local muscular necrosis and/or gangrene. In addition, anticoagulation syndrome, thromboembolism and thrombotic microangiopathy have been reported in victims of particular snake species. Thiansookon, A., Rojnuckarin, P., 2008. Coagulopathy is a significant cause of both morbidity and mortality in these patients, either directly, or indirectly. Mahasandana, S., Rungruxsirivorn, Y., Chantarangkul, V., 1980. Rojnuckarin, P., Chanthawibun, W., Noiphrom, J., Pakmanee, N., Intragumtornchai, T., 2006. Specific advice about children with potential snakebite should be sought early from a clinical toxicologist (Poisons Information Centre 13 11 26, 24 hrs/day). Fibrinolysis: Fibrin degradation may be a physiologic response to coagulation activation by venoms. Snakebite-induced acute kidney injury in Latin America. WARNING: GRAPHIC CONTENT. The mechanisms of coagulation pathway activation are also different among venoms and some are able to activate at several points (Table 39.1). However, the damage caused by the snake is a high risk of infection if not properly treated. However, the latter effect displays a different consequence in larger animals, which are not the natural preys. Thrombotic microangiopathy after Russell’s viper (Daboia russelli) bite showing numerous schistocytes. Prognostic factors of green pit viper bites. Would you like email updates of new search results? Southeast Asian J. Trop. Therefore, coagulopathy is only a part of multi-systemic involvement from envenomation including muscular weakness, rhabdomyolysis, renal failure and hypotension. Similar to defibrination syndrome, PT and APTT are prolonged increasing the risk of bleeding. Disseminated intravascular coagulation in cases of snake bite (Echis carinatus). Snake venoms and coagulopathy. If you continue browsing the … On the other hand, prothrombin activators cause low factor V, VIII (thrombin substrates) and prothrombin in human victims (White, 2005). 1–11. Acute intrinsic renal failure and blood coagulation disorders after a snakebite in a dog. Toxicon 29, 491–502. J. Trop. 46, 122–125. It is unpredictable by hypersensitivity skin test and, therefore, close observation during administration is mandatory (Thiansookon and Rojnuckarin, 2008). AIM: We aimed to investigate the diagnostic utility of the WBCT20 for coagulopathy in Russell's viper envenoming. Kanjanabuch, T., Sitprija, V., 2008. 145, 207–211. Laboratory diagnosis is a key part of the treatment of snakebite coagulopathy. Blood was drawn by a 23 guage needle with syringe into K3EDTA and 3.2% sodium citrate vacutainers. The key treatment of snakebites is antivenom that can promptly reverse coagulopathy in most situations. BW. The pathogenesis is unknown. Consumptive coagulopathy: Defibrination syndrome is the most common hemorrhagic syndrome after snakebites. Anticoagulation syndrome (Some Australian elapids): Mulga snake (Pseudechis australis), Spotted back snake (Pseudechis guttatus), Collett’s snake (Pseudechis colletti), Death adder (Acanthophis spp. When the damaged red blood cells begin to accumulate or build up, it can prevent the kidneys from functioning properly. Hyaluronidases, proteolytic enzymes and inflammatory responses enhance systemic absorption, as well as local tissue damages. Coagulation defects in snake bite poisoning. J. Haematol. Diagnosis of a snake bite case depends upon history, examination, and simple laboratory investigations including arterial blood gases (ABG) and electrolytes, complete blood counting (CBC), coagulation studies (prothrombin time, fibrin degradation products, fibrinogen), creatinine phosphokinase level (CPK) and urine analysis for the presence of blood and/or myoglobin in urine [5]. Anoop Enjeti, MBBS, MD, FRCPA, Anoop Enjeti, MBBS, MD, FRCPA 1 Dept. Trop. The clue is the severe anemia and thrombocytopenia detectable when coagulation time is normal or near normal. ), Tiger snake and Taipan, South American rattlesnake (Crotalus durissus terrificus) and lance-head vipers (Bothrops spp. PT, may be used instead of clotting time, but the clinical data are more limited. Life-threatening envenoming by the Saharan horned viper (, Sharp, P.J., Berry, S.L., Spence, I., Howden, M.E., 1989. White, J., 2005. However, in some patients, especially bitten by weakly venomous snakes such as green pit vipers (Cryptelytrops albolabris), the maximal toxicity may be delayed up to 3 days after bites (Rojnuckarin et al., 1998). Hemotoxins: work on the blood coagulation system and may cause internal bleeding. Thrombotic microangiopathy: Russell’s viper (Daboia russelli), Horned vipers (Cerastes cerastes), Lowland viper (Proatheris superciliaris), Australian brown snakes (Pseudonaja spp. Southeast Asian J. Trop. (b) Coagulation, anticoagulation and fibrinolytic pathways are shown connected by arrowed lines. We aimed to assess the performance of the WBCT20 in diagnosis of venom induced consumption coagulopathy (VICC) in Russell's viper envenoming. Laboratory studies and clinical features in a case of boomslang envenomation. Google Scholar. The toxins can be activating or inhibitory, either via protein-protein interactions or enzymatic proteolysis. They can be stimulatory or inhibitory through enzymatic or binding mechanisms. Warrell, D.A., 1989. Emerg. ), Red necked keelbacks (Rhabdophis spp. The extrinsic tenase complex (Tissue factor/factor VIIa) activates intrinsic tenase complex (Factor VIIIa/IXa on phospholipid surface) and prothrombinase complex (Factor Xa/Va on phospholipid surface) resulting in thrombin generation and, finally, fibrin formation. snake bite. Snake envenoming is being increasingly recognized as a major medical problem in tropical and subtropical countries. Only a subset of patients shows clinical bleeding. Furthermore, some SVMPs can degrade platelet receptor or their ligands, such as vWF, contributing to hemorrhage. Systemic rhabdomyolysis is the prominent feature of sea snakes, although it has been reported in conjunction with hematotoxicity from other snakes. Neuromuscular blockade in the presence of hemorrhagic diathesis (Gold et al., 2004; Warrell, 1989; White, 1998) is caused by selected Australians elapids, which are Tiger snake (Notechis spp. Quick video to show the effect of Malayan Pit Viper (Calloselasma rhodostoma) venom on blood. Neutralization of local tissue damage induced by. Ligands are displayed in the boxes close to their receptors. Systemic antivenom and skin necrosis after green pit viper bites. In addition, thrombosis has been reported early after other snakebites probably from rapid and strong procoagulant effects of the venoms prior to fibrinolytic activation. Isbister, G.K., 2009. Renal failure (Kanjanabuch and Sitprija, 2008; Pinho et al., 2008) may be a combinatorial result from direct kidney toxicity, indirect toxicity via cytokines, renal hypoperfusion, rhabdomyolysis (myoglobinuria), hemolysis (hemoglobinuria), disseminated intravascular coagulation, and/or thrombotic microangiopathy (discussed below). Schistocytes on blood smear (Fig. 39.2), red serum, hemoglobinuria and elevation of lactate dehydrogenase enzyme, as well as unconjugated bilirubin, are seen. Venombin B: Copperhead (Agkistrodon contortrix contortrix), Chinese Habu (Protobothrops mucrosquamatus), Halys vipers (Gloydius halys), iii. Platelet activation: Several C-type lectin-like proteins (CLPs) activates von Willebrand factor (vWF) receptor (Gp Ib/IX/V), collagen receptors (Integrin α2β1 and Gp VI) and the novel CLEC-2 receptor on platelet surface. Failure of antivenom to improve recovery in Australian snakebite coagulopathy. Idiopathic thrombotic microangiopathy is caused by vWF cleaving protease deficiency and/or endothelial injury resulting in platelet aggregation by unusually large vWF multimer secreted from endothelium. An activator of blood coagulation factor X from the venom of, © Springer Science+Business Media B.V. 2010, Division of Hematology, Department of Medicine, King Chulalongkorn Memorial Hospital and Chulalongkorn University, https://doi.org/10.1007/978-90-481-9295-3_39. SA. Furthermore, toxins may directly digest fibrin clot or indirectly activate plasminogen to plasmin. Snake venoms in science and clinical medicine. 58, 22–25. Search for other works by this author on: This Site. Thromboelastography (TEG) could help to understand these effects in … COVID-19 is an emerging, rapidly evolving situation. A thrombin-like enzyme from bushmaster (. Department of Small Animal Clinical Sciences, University of Florida, Gainesville, FL, USA 32610‐0126. Visudhiphan, S., Dumavibhat, B., Trishnananda, M., 1981. The current key treatment for hemostatic disorders is antivenom, the polyclonal IgG or parts of IgG purified from immunized horses or sheep. The quick coagulation or blood clotting caused by the Russell's viper venom is of particular interest to scientists — there's a lot of research into how it might be used in medicine. Chotenimitkhun, R., Rojnuckarin, P., 2008. Hyg. 1. Consumptive coagulopathy caused by a boomslang bite. Pathol. Moreover, textilinin-1, the antiplasmin from Pseudonaja textilis, has been isolated and used as a hemostatic agent (Flight et al., 2009). Google Scholar . Med. Med. Part of Springer Nature. Am. In addition, some CLPs are inhibitory by binding and competing with the natural platelet receptor ligands. Australian elapids: Brown snakes (Pseudonaja spp. Saini RK, Arya RK, Singh S, Sharma S, Gupta VK, Pathania NS. Due to the ethical issues, there has been no placebo-controlled trial to prove it efficacy. ), i. Am J Clin. Cite as. This is probably the main mechanism of fibrinolysis. Multiple cerebral infarctions following a snakebite by, 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. Antivenom is able to neutralize venom enzyme activity in vitro (Muanpasitporn and Rojnuckarin, 2007) and probably stop the consumptive process. This service is more advanced with JavaScript available, Toxins and Hemostasis In addition, plasma fibrinolytic activity is variable depending on the venom constituents. Gold, B.S., Barish, R.A., Dart, R.C., 2004. Zhang, Y., Xiong, Y.L., Bon, C., 1995. This hypothesis is also used to explain sporadic sudden cardiac death early after the brown snake bites (White, 2005). 51, 173–175. Acute intrinsic renal failure was diagnosed in a two-year-old, male, German shepherd dog following a Vipera aspis bite. In contrast to thrombin, they lack the complete effects and release only one of the fibrinopeptide A (venombin A) or fibrinopeptide B (venombin B). ), Rough scaled snake (Tropidechis carinatus), Broad head snakes (Hoplocephalus spp. For example, systemic hyperfibrinolysis defined as elevation of plasma plasminogen activator activity was found in green pit viper, but not in Russell’s viper bites (Than-Than et al., 1988). Puig J(1), Vilafranca M, Font A, Closa J, Pumarola M, Mascort J. The whole blood clotting test (WBCT) is a simple but critical bedside gross examination used in the assessment, diagnosis, and therapeutic monitoring of snakebite patients in the developing world and remote environments.