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Snake Venoms pp 417–436Cite as

Snake Venom Components Affecting the Coagulation System

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Part of the book series: Toxinology ((TOXI))

Abstract

Snake venoms are rich sources of proteases of medical importance that affect hemostasis. In this chapter, the factors affecting blood coagulation are classified into two separate groups: the procoagulant and the anticoagulant proteins. The procoagulant proteins are subclassified as clotting factor activators and thrombin-like enzymes. The anticoagulant proteins are able to prevent blood clotting and maintain blood incoagulability and can include phospholipases A2, fibrin(ogen)olytics, protein C activator, and L-amino acid oxidase (enzymatic anticoagulants) or C-type lectin-like proteins, three-finger toxins (TFTs), and Kunitz-type proteinase inhibitors (nonenzymatic anticoagulants). The study of toxins from snake affecting blood coagulation contributed to the current understanding of the mechanism of activation and inhibition of clotting factors. Moreover, they have been useful in the therapeutic area, for example, as defibrinogenating agents (thrombin-like enzymes) and as antithrombotic agents (fibrinolytic enzymes). Here, the recent findings will be introduced.

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References

  • Al Dieri R, Bloemen S, Kelchtermans H, Wagenvoord R, Hemker HC. A new regulatory function of activated factor V: inhibition of the activation by tissue factor/factor VII(a) of factor X. J Thromb Haemost. 2013;11(3):503–11.

    Article  CAS  PubMed  Google Scholar 

  • Andrade SA. Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation. Braz J Med Biol Res. 2012;45(10):929–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bezeaud A, Miyata T, Helley D, Zeng YZ, Kato H, Aillaud MF, Juhan-Vague I, Guillin MC. Functional consequences of the Ser334→Pro mutation in a human factor X variant (factor XMarseille). Eur J Biochem. 1995;234:140–7.

    Article  CAS  PubMed  Google Scholar 

  • Bjarnason JB, Fox JW. Hemorrhagic metalloproteinases from snake venoms. Pharmacol Ther. 1994;62(3):325–72.

    Article  CAS  PubMed  Google Scholar 

  • Cramer TJ, Gale AJ. The anticoagulant function of coagulation factor V. Thromb Haemost. 2012;107(1):15–21.

    Article  CAS  PubMed  Google Scholar 

  • Crowther MA, Warketin TE. Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents. Blood. 2008;111:4871–9.

    Article  CAS  PubMed  Google Scholar 

  • Das D, Sharma M, Kumar Das H, Pratim Sahu P, Doley R. Purification and characterization of Nk-3FTx: a three finger toxin from the Venom of North East Indian Monocled Cobra. J Biochem Mol Toxicol. 2016;30(2):59–70.

    Article  CAS  PubMed  Google Scholar 

  • De Morais NC, Neves Mamede CC, Fonseca KC, de Queiroz MR, Gomes-Filho SA, Santos-Filho NA, Bordon Kde C, Beletti ME, Sampaio SV, Arantes EC, De Oliveira F. Isolation and characterization of moojenin, an acid-active, anticoagulant metalloproteinase from Bothrops moojeni venom. Toxicon. 2012;60(7):1251–8.

    Article  PubMed  Google Scholar 

  • Dempfle CE, Alesci S, Kucher K, Müller-Peltzer H, Rübsamen K, Borggrefe M. Plasminogen activation without chances in tPA and PAI-1 in response to subcutaneous administration of ancrod. Thromb Res. 2001;104:433–8.

    Article  CAS  PubMed  Google Scholar 

  • Eley KA, Parker RJ, Watt-Smith SR. Low molecular weight heparin in patients undergoing free tissue transfer following head and neck ablative surgery: review of efficacy and associated complications. Br J Oral Maxillofac Surg. 2013;51(7):610–4.

    Article  PubMed  Google Scholar 

  • Fay WP, Owen WG. Platelet plasminogen activator inhibitor: purification and characterization of interaction with plasminogen activators and activated protein C. Biochemistry. 1989;28:5773–8.

    Google Scholar 

  • Sakamoto T, Ogawa H, Takazoe K, Yoshimura M, Shimomura H, Moriyama Y, Arai H, Okajima K. Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase: comparison with unfractionated heparin. J Am Coll Cardiol. 2003;42:1389–94.

    Google Scholar 

  • Fox JW, Serrano SM. Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to snake venom complexity. FEBS J. 2008;275(12):3016–30.

    Article  CAS  PubMed  Google Scholar 

  • Gempeler-Messina PM, Volz K, Bühler B, Müller C. Protein C activators from snake venoms and their diagnostic use. Haemostasis. 2001;31(3–6):266–72.

    CAS  PubMed  Google Scholar 

  • Hoffman M, Monroe DM. Coagulation 2006: a modern view of hemostasis. Hematol Oncol Clin North Am. 2007;21(1):1–11.

    Article  PubMed  Google Scholar 

  • Izidoro LF, Sobrinho JC, Mendes MM, Costa TR, Grabner AN, Rodrigues VM, da Silva SL, Zanchi FB, Zuliani JP, Fernandes CF, Calderon LA, Stábeli RG, Soares AM. Snake venom l-amino acid oxidases: trends in pharmacology and biochemistry. Biomed Res Int. 2014;2014:196754.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kini RM. Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes. Toxicon. 2003;42(8):827–40.

    Article  CAS  PubMed  Google Scholar 

  • Kini RM. Structure-function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms. Toxicon. 2005a;45(8):1147–61.

    Article  CAS  PubMed  Google Scholar 

  • Kini RM. The intriguing world of prothrombin activators from snake venoms. Toxicon. 2005b;45:1133–45.

    Article  CAS  PubMed  Google Scholar 

  • Kini RM. Anticoagulant proteins from snake venoms: structure, function and mechanism. Biochem J. 2006;397(3):377–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kini RM, Banerjee Y. Dissection approach: a simple strategy for the identification of the step of action of anticoagulant agents in the blood coagulation cascade. J Thromb Haemost. 2005;3(1):170–1.

    Article  CAS  PubMed  Google Scholar 

  • Kini RM, Evans HJ. The role of enzymatic activity in inhibition of the extrinsic tenase complex by phospholipase A2 isoenzymes from Naja nigricollis venom. Toxicon. 1995;33(12):1585–90.

    Article  CAS  PubMed  Google Scholar 

  • Koh Y, Chung K, Kim D. Purification and cDNA cloning of salmorin that inhibits fibrinogen clotting. Thromb Res. 2000;99(4):389–98.

    Article  CAS  PubMed  Google Scholar 

  • Koh DC, Armugam A, Jeyaseelan K. Snake venom components and their applications in biomedicine. Cell Mol Life Sci. 2006;63:3030–41.

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Counssel C, Zhao XL, Wardlaw J. Fibrinogen depleting agents for acute ischaemic stroke. Cochrane Database Syst Rev. 2003;3, CD000091.

    Google Scholar 

  • Lomonte B, Fernandez J, Sanz L, Angulo Y, Sasa M, Gutierrez JM, Calvete JJ. Venomous snakes of Costa Rica: biological and medical implications of their venom proteomic profiles analyzed through the strategy of snake venomics. J Proteomics. 2014;105:323–39.

    Article  CAS  PubMed  Google Scholar 

  • Lövgren A. Recombinant snake venom prothrombin activators. Bioengineered. 2013;4(3):153–7.

    Article  PubMed  Google Scholar 

  • Lu Q, Clemetson JM, Clemetson KJ. Snake venoms and hemostasis. J Thromb Haemost. 2005;3:1791–9.

    Article  CAS  PubMed  Google Scholar 

  • Maduwage K, Buckley NA, de Silva HJ, Lalloo DG, Isbister GK. Snake antivenom for snake venom induced consumption coagulopathy. Cochrane Database Syst Rev. 2015. doi:10.1002/14651858.CD011428.pub2.

    PubMed  Google Scholar 

  • Markland Jr FS, Swenson S. Snake venom metalloproteinases. Toxicon. 2013;62:3–18.

    Article  CAS  PubMed  Google Scholar 

  • Marsh NA. Diagnostic uses of snake venom. Haemostasis. 2001;31:211–7.

    CAS  PubMed  Google Scholar 

  • Marsh N, Williams V. Practical applications of snake venom toxins in haemostasis. Toxicon. 2005;45(8):1171–81.

    Article  CAS  PubMed  Google Scholar 

  • McCleary RJ, Kini RM. Snake bites and hemostasis/thrombosis. Thromb Res. 2013;132:624–46.

    Article  Google Scholar 

  • Moore GM. Recent guidelines and recommendations for laboratory detection of lúpus anticoagulants. Semin Thromb Hemost. 2014;40:163–71.

    Article  CAS  PubMed  Google Scholar 

  • Morita T. C-type lectin-related proteins from snake venoms. Curr Drug Targets Cardiovasc Haematol Disord. 2004;4(4):357–73.

    Article  CAS  PubMed  Google Scholar 

  • Nakayama D, Ben Ammar Y, Miyata T, Takeda S. Structural basis of coagulation factor V recognition for cleavage by RVV-V. FEBS Lett. 2011;585(19):3020–5.

    Article  CAS  PubMed  Google Scholar 

  • Oliveira-Carvalho AL, Guimarães PR, Abreu PA, Dutra DL, Junqueira-de-Azevedo IL, Rodrigues CR, Ho PL, Castro HC, Zingali RB. Identification and characterization of a new member of snake venom thrombin inhibitors from Bothrops insularis using a proteomic approach. Toxicon. 2008;51(4):659–71.

    Article  CAS  PubMed  Google Scholar 

  • Qin J, Xu Z, Shi D, Chen D, Dai J, Teng H, Jiang Q. Deep vein thrombosis after total hip arthroplasty and total knee arthroplasty in patients with previous ischemic stroke. Int J Low Extrem Wounds. 2013;12(2):316–9.

    Article  PubMed  Google Scholar 

  • Sajevic T, Leonardi A, Krizaj I. Haemostatically active proteins in snake venoms. Toxicon. 2011;57:627–45.

    Article  CAS  PubMed  Google Scholar 

  • Sakurai Y, Shima M, Matsumoto T, Takatsuka H, Nishiya K, Kasuda S, Fujimura Y, Yoshioka A. Anticoagulant activity of M-LAO, l-amino acid oxidase purified from Agkistrodon halys blomhoffii, through selective inhibition of factor IX. Biochim Biophys Acta. 2003;1649(1):51–7.

    Article  CAS  PubMed  Google Scholar 

  • Schöni R. The use of snake venom-derived compounds for new functional diagnostics test kits in the field of haemostasis. Pathophysiol Haemost Thromb. 2005;34:234–40.

    Article  PubMed  Google Scholar 

  • Segers K, Rosing J, Nicolaes GA. Structural models of the snake venom factor V activators from Daboia russelli and Daboia lebetina. Proteins. 2006;64:968–84.

    Article  CAS  PubMed  Google Scholar 

  • Serrano SM. The long road of research on snake venom serine proteinases. Toxicon. 2013;62:19–26.

    Article  CAS  PubMed  Google Scholar 

  • Serrano SM, Shannon JD, Wang D, Camargo AC, Fox JW. A multifaceted analysis of viperid snake venoms by two-dimensional gel electrophoresis: an approach to understanding venom proteomics. Proteomics. 2005;5(2):501–10.

    Article  CAS  PubMed  Google Scholar 

  • Siigur J, Siigur E. Factor X activating proteases from snake venoms. Tox Rev. 2006;25:235–55.

    Article  CAS  Google Scholar 

  • Stefansson S, Kini RM, Evans HJ. The inhibition of clotting complexes of the extrinsic coagulation cascade by the phospholipase A2 isoenzymes from Naja nigricollis venom. Thromb Res. 1989;55(4):481–91.

    Article  CAS  PubMed  Google Scholar 

  • Stefansson S, Kini RM, Evans HJ. The basic phospholipase A2 from Naja nigricollis venom inhibits the prothrombinase complex by a novel nonenzymatic mechanism. Biochemistry. 1990;29(33):7742–6.

    Article  CAS  PubMed  Google Scholar 

  • Swenson S, Markland FS. Snake venom fibrin(ogen)olytic enzymes. Toxicon. 2005;45:1021–39.

    Article  CAS  PubMed  Google Scholar 

  • Takeda S, Igarashi T, Mori H. Crystal structure of RVV-X: an example of evolutionary gain of specificity by ADAM proteinases. FEBS Lett. 2007;581(30):5859–64. Epub 2007 Dec 3.

    Article  CAS  PubMed  Google Scholar 

  • Takeya H, Nishida S, Miyata T, Kawada S, Saisaka Y, Morita T, Iwanaga S. Coagulation factor X activating enzyme from Russell’s viper venom (RVV-X). A novel metalloproteinase with disintegrin (platelet aggregation inhibitor)-like and C-type lectin-like domains. J Biol Chem. 1992;267(20):14109–17.

    CAS  PubMed  Google Scholar 

  • Thakur R, Chattopadhyay P, Ghosh SS, Mukherjee AK. Elucidation of procoagulant mechanism and pathophysiological significance of a new prothrombin activating metalloprotease purified from Daboia russelii russelii venom. Toxicon. 2015;100:1–12.

    Article  CAS  PubMed  Google Scholar 

  • Triplett DA. Use of the dilute Russell viper venom time (dRVVT): its importance and pitfalls. J Autoimmun. 2000;15:173–8.

    Article  CAS  PubMed  Google Scholar 

  • Zelanis A, Menezes MC, Kitano ES, Liberato T, Tashima AK, Pinto AF, Sherman NE, Ho PL, Fox JW, Serrano SM. Proteomic identification of gender molecular markers in Bothrops jararaca venom. J Proteomics. 2016. doi:10.1016/j.jprot.2016.02.030.

    Google Scholar 

  • Zingali RB, Ferreira MS, Assafim M, Frattani FS, Monteiro RQ. Bothrojaracin, a Bothrops jararaca snake venom-derived (pro)thrombin inhibitor, as an anti-thrombotic molecule. Pathophysiol Haemost Thromb. 2005;34(4–5):160–3.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Biochemistry Laboratory, Butantan Institute, São Paulo, Brazil

    Miryam Paola Alvarez-Flores, Fernanda Faria, Sonia Aparecida de Andrade & Ana Marisa Chudzinski-Tavassi

Authors
  1. Miryam Paola Alvarez-Flores
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  2. Fernanda Faria
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  3. Sonia Aparecida de Andrade
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  4. Ana Marisa Chudzinski-Tavassi
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Corresponding authors

Correspondence to Miryam Paola Alvarez-Flores , Fernanda Faria , Sonia Aparecida de Andrade or Ana Marisa Chudzinski-Tavassi .

Editor information

Editors and Affiliations

  1. Biomedical Research Institute National Institute of Advanced Industria, Tsukuba, Ibaraki, Japan

    Hidetoshi Inagaki

  2. University of Hawaii Cancer Center, Honolulu, Hawaii, USA

    Carl-Wilhelm Vogel

  3. Department of Molecular Biology and Biot, Tezpur University, Tezpur, Assam, India

    Ashis K. Mukherjee

  4. Egyptian Society of Natural Toxins and Z, Faculty of Science Suez Canal University, Ismailia, Egypt

    Tarek R. Rahmy

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© 2017 Springer Science+Business Media Dordrecht

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Alvarez-Flores, M.P., Faria, F., de Andrade, S.A., Chudzinski-Tavassi, A.M. (2017). Snake Venom Components Affecting the Coagulation System. In: Inagaki, H., Vogel, CW., Mukherjee, A., Rahmy, T. (eds) Snake Venoms. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6410-1_31

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