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Thromboelastography with Platelet Studies (TEG® with PlateletMapping®) After Rattlesnake Envenomation in the Southwestern United States Demonstrates Inhibition of ADP-Induced Platelet Activation As Well As Clot Lysis

  • A. Min KangEmail author
  • Erik S. Fisher
Original Article
  • 5 Downloads

Abstract

Introduction

Hematologic effects of North American rattlesnake envenomation can include fibrinogenolysis and thrombocytopenia, depending on species, geography, and other variables. During treatment, these effects are routinely monitored through assessment of fibrinogen concentrations and platelet counts. However, these tests provide no information about fibrinolysis or platelet dysfunction, both of which can also occur with venom from some species.

Methods

This was a retrospective chart review of patients admitted to a quaternary care academic hospital (Banner – University Medical Center Phoenix) in the southwestern United States for treatment of rattlesnake envenomation, over an approximately 1-year period from March 2017 through April 2018. Patients who had thromboelastography with platelet studies (TEG® with PlateletMapping®) during their care were included.

Results

Twelve patients were identified for this study. Four patients exhibited inhibition of ADP-induced platelet activation: one had normal fibrinogen and platelet count, two had concurrent hypofibrinogenemia, and one had concurrent thrombocytopenia. Crotalidae polyvalent immune Fab (ovine) reversed platelet inhibition in the single patient for whom serial thromboelastographs were available. Fibrinolysis was present in seven patients and resolved in the two patients with serial thromboelastographs.

Conclusions

Inhibition of ADP-induced platelet aggregation and fibrinolysis occurred independent of hypofibrinogenemia and thrombocytopenia, indicating fibrinogen concentration (or protime) and platelet count monitoring alone is insufficient to assess the extent of hematologic toxicity in rattlesnake envenomation. Crotalidae polyvalent immune Fab (ovine) reversed platelet inhibition in one case, suggesting platelet inhibition could also be used in treatment decisions. Fibrinolysis could also be reversed, although the timing to antivenom administration was less clear.

Keywords

Thromboelastography (TEG) with PlateletMapping Platelet activation Rattlesnake envenomation Antivenom Fibrinolysis 

Notes

Compliance with Ethical Standards

Conflicts of Interest

None

References

  1. 1.
    Camilleri R. A meta-analysis of the reliability of the history in suspected poisoning. J Emerg Med. 2015;48(6):679–84.  https://doi.org/10.1016/j.jemermed.2014.12.067.CrossRefGoogle Scholar
  2. 2.
    Kitchens CS, Van Mierop LH. Mechanism of defibrination in humans after envenomation by the eastern diamondback rattlesnake. Am J Hematol. 1983;14(4):345–53.  https://doi.org/10.1002/ajh.2830140405.CrossRefGoogle Scholar
  3. 3.
    Miller AD, Young MC, DeMott MC, Ly BT, Clark RF. Recurrent coagulopathy and thrombocytopenia in children treated with crotalidae polyvalent immune fab: a case series. Pediatr Emerg Care. 2010;26(8):576–82.  https://doi.org/10.1097/PEC.0b013e3181ea722b.CrossRefGoogle Scholar
  4. 4.
    Ruha AM, Kleinschmidt KC, Greene S, Spyres MB, Brent J, Wax P, et al. The epidemiology, clinical course, and management of snakebites in the North American Snakebite Registry. J Med Toxicol. 2017;13(4):309–20.  https://doi.org/10.1007/s13181-017-0633-5.CrossRefGoogle Scholar
  5. 5.
    Budzynski AZ, Pandya BV, Rubin RN, Brizuela BS, Soszka T, Stewart GJ. Fibrinogenolytic afibrinogenemia after envenomation by western diamondback rattlesnake (Crotalus atrox). Blood. 1984;63(1):1–14.Google Scholar
  6. 6.
    Zhou Q, Smith JB, Grossman MH. Molecular cloning and expression of catrocollastatin, a snake-venom protein from Crotalus atrox (western diamondback rattlesnake) which inhibits platelet adhesion to collagen. Biochem J. 1995;307(Pt 2):411–7.CrossRefGoogle Scholar
  7. 7.
    Sanchez EE, Galan JA, Russell WK, Soto JG, Russell DH, Perez JC. Isolation and characterization of two disintegrins inhibiting ADP-induced human platelet aggregation from the venom of Crotalus scutulatus scutulatus (Mohave rattlesnake). Toxicol Appl Pharmacol. 2006;212(1):59–68.  https://doi.org/10.1016/j.taap.2005.07.004.CrossRefGoogle Scholar
  8. 8.
    Carstairs SD, Kreshak AA, Tanen DA. Crotaline Fab antivenom reverses platelet dysfunction induced by Crotalus scutulatus venom: an in vitro study. Acad Emerg Med. 2013;20(5):522–5.  https://doi.org/10.1111/acem.12135.CrossRefGoogle Scholar
  9. 9.
    Castellino FJ, Liang Z, Davis PK, Balsara RD, Musunuru H, Donahue DL, et al. Abnormal whole blood thrombi in humans with inherited platelet receptor defects. PLoS One. 2012;7(12):e52878.  https://doi.org/10.1371/journal.pone.0052878.CrossRefGoogle Scholar
  10. 10.
    Lavonas EJ, Ruha AM, Banner W, Bebarta V, Bernstein JN, Bush SP, et al. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med. 2011;11:2.  https://doi.org/10.1186/1471-227X-11-2.CrossRefGoogle Scholar
  11. 11.
    Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfus Med Rev. 2012;26(1):1–13.  https://doi.org/10.1016/j.tmrv.2011.07.005.CrossRefGoogle Scholar
  12. 12.
    Hadley GP, McGarr P, Mars M. The role of thromboelastography in the management of children with snake-bite in southern Africa. Trans R Soc Trop Med Hyg. 1999;93(2):177–9.  https://doi.org/10.1016/s0035-9203(99)90300-0.CrossRefGoogle Scholar
  13. 13.
    Larreche S, Jean FX, Benois A, Mayet A, Bousquet A, Vedy S, et al. Thromboelastographic study of the snakebite-related coagulopathy in Djibouti. Blood Coagul Fibrinolysis. 2018;29(2):196–204.  https://doi.org/10.1097/MBC.0000000000000702.Google Scholar
  14. 14.
    Nag I, Datta SS, De D, Pal P, Das SK. Role of thromboelastography in the management of snake bite: a case report from India. Transfus Apher Sci. 2017;56(2):127–9.  https://doi.org/10.1016/j.transci.2016.10.003.
  15. 15.
    Roszko PJD, Kavanaugh MJ, Boese ML, Longwell JJ, Earley AS. Rotational thromboelastometry (ROTEM) guided treatment of an Afghanistan viper envenomation at a NATO military hospital. Clin Toxicol. 2017;55:1–2.  https://doi.org/10.1080/15563650.2016.1263857.CrossRefGoogle Scholar
  16. 16.
    Cao D, Domanski K, Hodgman E, Cardenas C, Weinreich M, Hutto J, et al. Thromboelastometry analysis of severe North American pit viper-induced coagulopathy: a case report. Toxicon. 2018;151:29–33.  https://doi.org/10.1016/j.toxicon.2018.06.079.CrossRefGoogle Scholar
  17. 17.
    Leffers P, Ferreira J, Sollee D, Schauben J. Thromboelastography in the management of snakebite-induced coagulopathy: a case series and literature review. Blood Coagul Fibrinolysis. 2018;29(7):656–60.  https://doi.org/10.1097/MBC.0000000000000771.Google Scholar
  18. 18.
    McBride KM, Bromberg W, Dunne J. Thromboelastography utilization in delayed recurrent coagulopathy after severe eastern diamondback rattlesnake envenomation. Am Surg. 2017;83(4):332–6.Google Scholar
  19. 19.
    Nielsen VG, Boyer LV. Iron and carbon monoxide attenuate degradation of plasmatic coagulation by Crotalus atrox venom. Blood Coagul Fibrinolysis. 2016;27(5):506–10.  https://doi.org/10.1097/MBC.0000000000000440.CrossRefGoogle Scholar
  20. 20.
    Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.  https://doi.org/10.1016/j.jbi.2008.08.010.CrossRefGoogle Scholar
  21. 21.
    Fisher E, Kang AM. A case of rattlesnake venom-induced platelet inhibition reversed by crotalidae polyvalent immune fab as demonstrated by thromboelastography. Clin Toxicol. 2018;56(10):1020–92.  https://doi.org/10.1080/15563650.2018.1506610.Google Scholar
  22. 22.
    Bochsen L, Wiinberg B, Kjelgaard-Hansen M, Steinbruchel DA, Johansson PI. Evaluation of the TEG platelet mapping assay in blood donors. Thromb J. 2007;5:3.  https://doi.org/10.1186/1477-9560-5-3.CrossRefGoogle Scholar
  23. 23.
    Carroll RC, Craft RM, Chavez JJ, Snider CC, Kirby RK, Cohen E. Measurement of functional fibrinogen levels using the Thrombelastograph. J Clin Anesth. 2008;20(3):186–90.  https://doi.org/10.1016/j.jclinane.2007.09.017.CrossRefGoogle Scholar
  24. 24.
    Bajwa SS, Markland FS, Russell FE. Fibrinolytic enzyme(s) in western diamondback rattlesnake (Crotalus atrox) venom. Toxicon. 1980;18(3):285–90.  https://doi.org/10.1016/0041-0101(80)90007-0.CrossRefGoogle Scholar
  25. 25.
    Bajwa SS, Markland FS, Russell FE. Fibrinolytic and fibrinogen clotting enzymes present in the venoms of western diamondback rattlesnake, Crotalus atrox, eastern diamondback rattlesnake, Crotalus adamanteus, and southern pacific rattlesnake, Crotalus viridis helleri. Toxicon. 1981;19(1):53–9.  https://doi.org/10.1016/0041-0101(81)90117-3.CrossRefGoogle Scholar
  26. 26.
    Reid HA, Theakston RDG. Changes in coagulation effects by venoms of Crotalus atrox as snakes age. Am J Trop Med Hyg. 1978;27(5):1053–7.Google Scholar
  27. 27.
    Gregory VM, Russell FE, Brewer JR, Zawadski LR. Seasonal variations in rattlesnake venom proteins. Proc West Pharmacol Soc. 1984;27:233–6.Google Scholar
  28. 28.
    Tseng YL, Chiang ML, Lane HY, Su KP, Lai YC. Selective serotonin reuptake inhibitors reduce P2Y12 receptor-mediated amplification of platelet aggregation. Thromb Res. 2013;131(4):325–32.  https://doi.org/10.1016/j.thromres.2013.02.007.CrossRefGoogle Scholar
  29. 29.
    Bismuth-Evenzal Y, Gonopolsky Y, Gurwitz D, Iancu I, Weizman A, Rehavi M. Decreased serotonin content and reduced agonist-induced aggregation in platelets of patients chronically medicated with SSRI drugs. J Affect Disord. 2012;136(1–2):99–103.  https://doi.org/10.1016/j.jad.2011.08.013.CrossRefGoogle Scholar
  30. 30.
    Roweth HG, Cook AA, Moroi M, Bonna AM, Jung SM, Bergmeier W, et al. Two novel, putative mechanisms of action for citalopram-induced platelet inhibition. Sci Rep. 2018;8(1):16677.  https://doi.org/10.1038/s41598-018-34389-5.CrossRefGoogle Scholar

Copyright information

© American College of Medical Toxicology 2019

Authors and Affiliations

  1. 1.Department of Child Health; and Department of Medicine, Division of Medical Toxicology and Precision MedicineUniversity of Arizona College of Medicine – PhoenixPhoenixUSA
  2. 2.Department of Medical ToxicologyBanner – University Medical Center PhoenixPhoenixUSA
  3. 3.Department of Medicine, Section of ToxicologyPhoenix Children’s HospitalPhoenixUSA
  4. 4.Department of Medicine, Division of Medical Toxicology and Precision MedicineUniversity of Arizona College of Medicine – PhoenixPhoenixUSA

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