Volume 98, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Snake envenomation is a major public health problem in Brazil. Systemic complications that may arise from snakebites are mainly related to coagulopathy. The Lee–White clotting time (LWCT) is a simple and inexpensive test and available even in remote health facilities. However, the diagnostic value of such test needs to be evaluated to accurately diagnose coagulopathy in the clinical practice. This study aimed to assess the reliability of the LWCT performed in hospital routine to diagnose venom-induced coagulopathy. We studied 186 patients admitted at the Tropical Medicine Foundation Dr. Heitor Vieira Dourado in Manaus, Amazonas, Brazil, with envenomation diagnosis. At admission, blood samples were collected for performing LWCT and the concentration of fibrinogen. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios, diagnostic odds ratio, and accuracy were calculated with 95% confidence intervals. From the total, 85.5% had hypofibrinogenemia. The sensitivity of the LWCT to the diagnosis of hypofibrinogenemia was 78.0% and the specificity 40.7%. The accuracy of the test was 72.6%, and patients with a prolonged LWCT had 2.4 higher odds of developing hypofibrinogenemia. In addition, the LWCT was also compared with venom antigen levels and systemic hemorrhage. The LWCT showed moderate sensitivity to detect consumption coagulopathy and constitutes a valuable tool for the diagnosis of snake envenomation and indication of antivenom therapy.


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  1. Brazilian Ministry of Health, 2017. Sistema de Informação de Agravos de Notificação—SINAN. Brasília, Brazil: Brazilian Ministry of Health. Available at: http://tabnet.datasus.gov.br/cgi/tabcgi.exe?sinannet/cnv/animaisbr.def.
  2. Feitosa EL, 2015. Older age and time to medical assistance are associated with severity and mortality of snakebites in the Brazilian Amazon : a case-control study. PLoS One 10: 115. [Google Scholar]
  3. Warrell DA, , 2010. Guidelines for the Clinical Management of Snake Bites. New Delhi, India: WHO Regional Office for Southeast Asia.
  4. Feitosa ES, 2015. Snakebites as a largely neglected problem in the Brazilian Amazon: highlights of the epidemiological trends in the state of Amazonas. Rev Soc Bras Med Trop 48: 3441. [Google Scholar]
  5. Assakura MT, de Fatima Furtado M, Mandelbaum FR, , 1992. Biochemical and biological differentiation of the venoms of the lancehead vipers (Bothrops atrox, Bothrops asper, Bothrops marajoensis and Bothrops moojeni). Comp Biochem Physiol Part B Biochem 102: 727732. [Google Scholar]
  6. López-Lozano JL, de Sousa MV, Ricart CAO, Chávez-Olortegui C, Flores Sanchez E, Muniz EG, Bührnheim PF, Morhy L, , 2002. Ontogenetic variation of metalloproteinases and plasma coagulant activity in venoms of wild Bothrops atrox specimens from Amazonian rain forest. Toxicon 40: 9971006. [Google Scholar]
  7. Jacob-Ferreira AL, Menaldo DL, Bernardes CP, Sartim MA, De Angelis CD, Tanus-Santos JE, Sampaio SV, , 2016. Evaluation of the in vivo thrombolytic activity of a metalloprotease from Bothrops atrox venom using a model of venous thrombosis. Toxicon 109: 1825. [Google Scholar]
  8. Sanchez EF, Schneider FS, Yarleque A, Borges MH, Richardson M, Figueiredo SG, Evangelista KS, Eble JA, , 2010. The novel metalloproteinase atroxlysin-I from Peruvian Bothrops atrox (Jergón) snake venom acts both on blood vessel ECM and platelets. Arch Biochem Biophys 496: 920. [Google Scholar]
  9. Freitas-De-Sousa LA, Amazonas DR, Sousa LF, Sant’Anna SS, Nishiyama MY, Serrano SMT, Junqueira-De-Azevedo ILM, Chalkidis HM, Moura-Da-Silva AM, Mourão RHV, , 2015. Comparison of venoms from wild and long-term captive Bothrops atrox snakes and characterization of Batroxrhagin, the predominant class PIII metalloproteinase from the venom of this species. Biochimie 118: 6070. [Google Scholar]
  10. Freitas-de-Sousa LA, Colombini M, Lopes-Ferreira M, Serrano SMT, Moura-da-silva AM, , 2017. Insights into the mechanisms involved in strong hemorrhage and dermonecrosis induced by atroxlysin-Ia, a PI-class snake venom metalloproteinase. Toxins (Basel) 9: 239. [Google Scholar]
  11. Pardal PPO, 2004. Clinical trial of two antivenoms for the treatment of Bothrops and Lachesis bites in the north eastern Amazon region of Brazil. Trans R Soc Trop Med Hyg 98: 2842. [Google Scholar]
  12. Otero R, 2002. Complications of Bothrops, Porthidium, and Bothriechis snakebites in Colombia. A clinical and epidemiological study of 39 cases attended in a university hospital. Toxicon 40: 11071114. [Google Scholar]
  13. Souza ARB, , 2002. Snakebite by Bothrops atrox (Lin. 1758) in the state of Amazonas–Brazil: study of 212 cases with identified snake. Rev Patol Trop 31: 267268. [Google Scholar]
  14. Oliveira SS, Freitas-de-Sousa LA, Alves EC, Lima Ferreira LC, Silva IM, Lacerda MVG, Fan HW, Moura-da-Silva AM, Monteiro WM, , 2017. Fatal stroke after Bothrops snakebite in the Amazonas state, Brazil: a case report. Toxicon 138: 102106. [Google Scholar]
  15. Brazilian Ministry of Health, 2001. Manual de Diagnóstico e Tratamento de Acidentes por Animais Peçonhentos. Brasilia, Brazil: FUNASA, p. 112. Available at: http://bvsms.saude.gov.br/bvs/publicacoes/funasa/manu_peconhentos.pdf.
  16. Ratnayake I, Shihana F, Dissanayake DM, Buckley NA, Maduwage K, Isbister GK, , 2017. Performance of the 20-minute whole blood clotting test in detecting venom induced consumption coagulopathy from Russell’s viper (Daboia russelii) bites. Thromb Haemost 117: 500507. [Google Scholar]
  17. Sano-Martins IS, Fan HW, Castro SCB, Tomy SC, Franca FOS, Jorge MT, Kamiguti AS, Warrell DA, Theakston RDG, , 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. Toxicon 32: 10451050. [Google Scholar]
  18. Lee RI, White PD, , 1913. A clinical study of the coagulation time of blood. Am J Med Sci 145: 496503. [Google Scholar]
  19. Gaus DP, Herrera DF, Troya CJ, Guevara AH, , 2013. Management of snakebite and systemic envenomation in rural Ecuador using the 20-minute whole blood clotting test. Wilderness Environ Med 24: 345350. [Google Scholar]
  20. Isbister GK, Currie BJ, , 2003. Suspected snakebite: one year prospective study of emergency department presentations. J Emerg Med 15: 160169. [Google Scholar]
  21. Punguyire D, Iserson KV, Stolz U, Apanga S, , 2013. Bedside whole-blood clotting times: validity after snakebites. J Emerg Med 44: 663667. [Google Scholar]
  22. Isbister GK, Maduwage K, Shahmy S, Mohamed F, Abeysinghe C, Karunathilake H, Ariaratnam CA, Buckley NA, , 2013. Diagnostic 20-min whole blood clotting test in Russell’s viper envenoming delays antivenom administration. QJM 106: 925932. [Google Scholar]
  23. Isbister GK, Maduwage K, Scorgie FE, Shahmy S, Mohamed F, Abeysinghe C, Karunathilake H, O’Leary MA, Gnanathasan CA, Lincz LF, , 2015. Venom concentrations and clotting factor levels in a prospective cohort of Russell’s viper bites with coagulopathy. PLoS Negl Trop Dis 9: e0003968. [Google Scholar]
  24. Sutherland SK, Tibballs J, , 2001. Australian Animal Toxins. Melbourne, Australia: Oxford University Press.
  25. De Silva HAJ, Ryan NM, Silva HAJ, , 2016. Adverse reactions to snake antivenom, and their prevention and treatment. Br J Clin Pharmacol 81: 446452. [Google Scholar]
  26. Morais V, Berasain P, Ifrán S, Carreira S, Tortorella MN, Negrín A, Massaldi H, , 2012. Humoral immune responses to venom and antivenom of patients bitten by Bothrops snakes. Toxicon 59: 315319. [Google Scholar]
  27. León G, Herrera M, Segura Á, Villalta M, Vargas M, Gutiérrez JM, , 2013. Pathogenic mechanisms underlying adverse reactions induced by intravenous administration of snake antivenoms. Toxicon 76: 6376. [Google Scholar]
  28. Fan H, Marcopito L, Cardoso J, França F, Malaque C, Ferrari R, Theakston R, Warrell D, , 1999. Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for Bothrops snake bites. BMJ 318: 14511452. [Google Scholar]
  29. De Arruda MM, Figueiredo FB, Marcelino AP, Barbosa JR, Werneck GL, Noronha EF, Sierra Romero GA, , 2016. Sensitivity and specificity of parallel or serial serological testing for detection of canine Leishmania infection. Mem Inst Oswaldo Cruz 111: 168173. [Google Scholar]
  30. Sachett JAG, 2017. Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from Bothrops snakebites in the Brazilian Amazon: a randomized controlled clinical trial. PLoS Negl Trop Dis 11: e0005745. [Google Scholar]
  31. Stone R, Seymour J, Marshall O, , 2006. Plastic containers and the whole-blood clotting test: glass remains the best option. Trans R Soc Trop Med Hyg 100: 11681172. [Google Scholar]

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  • Received : 19 Dec 2017
  • Accepted : 15 Feb 2018
  • Published online : 02 Apr 2018

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