Diagnostic Use of Snake Venom Components in the Coagulation Laboratory

  • Anna Maria Perchuc
  • Marianne Wilmer


For almost every factor involved in haemostasis there exists a snake venom protein that can mimic, activate or deactivate it. Many of these compounds are insensitive to the physiological and therapeutically used coagulation inhibitors and, because of their unique features, are applied as molecular tools for diagnosis of haemostatic disorders. Different snake venom proteins are nowadays widely used in the coagulation laboratory and have facilitated extensively the routine assays of haemostatic parameters and understanding of basic biological mechanisms involved in the clotting and fibrinolysis processes. Some of these routine applications have been adopted as the preferred option of the diagnostic tests. The following parameters can be tested by means of snake venom components: antithrombin III, fibrinogen, its breakdown products and its dysfunctions, prothrombin and dysprothrombinaemias, blood clotting factors V, VII and X, lupus anticoagulants, protein C and its pathway, as well as activated protein C resistance, von Willebrand factor (vWF) and related syndromes. Further, immediately acting anticoagulants, such as heparins and direct thrombin inhibitors, which are among the most frequently applied drugs, can be monitored by an assay using snake venom enzyme.

Ongoing research leads to isolation and characterization of new snake venom components, which are potential tools for future applications in the field of haemostasis, in diagnostic as well as in therapeutic approaches.


Snake Venom Lupus Anticoagulant Prothrombin Activator Ecarin Clotting Time Snake Venom Toxin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Andrews, R.K., Kamiguti, A.S., Berlanga, O., Leduc, M., Theakston, R.D., Watson, S.P., 2001. The use of snake venom toxins as tools to study platelet receptors for collagen and von Willebrand factor. Haemostasis 31, 155–172.PubMedGoogle Scholar
  2. Baidoo, K.E., Knight, L.C., Lin, K.S., Gabriel, J.L., Romano, J.E., 2004. Design and synthesis of a short-chain bitistatin analogue for imaging thrombi and emboli. Bioconjug. Chem. 15, 1068–1075.PubMedCrossRefGoogle Scholar
  3. Bachmann, F., Duckert, F., Koller, F., 1958. The Stuart–Prower assay and its clinical significance. Thromb. Diath. Haemorrh. 2, 24–38.PubMedGoogle Scholar
  4. Braud, S., Bon, C., Wisner, A., 2000. Snake venom proteins acting on hemostasis. Biochimie 82, 851–859.PubMedCrossRefGoogle Scholar
  5. Brinkhous, K.M., Read, M.S., Fricke, W.A., Wagner, R.H., 1983. Botrocetin (venom coagglutinin): reaction with a broad spectrum of multimeric forms of factor VIII macromolecular complex. Proc. Natl. Acad. Sci. U.S.A. 80, 1463–1466.PubMedCrossRefGoogle Scholar
  6. Brinkhous, K.M., Smith, S.V., Read, M.S., 1988. Botrocetin and von Willebrand factor, in: Pirkle, H., Markland, F.S., Jr. (Eds.), Hemostasis and Animal Venoms. Marcel Dekker Inc., New York, pp. 377–398.Google Scholar
  7. Calatzis, A., Peetz, D., Haas, S., Spannagl, M., Rudin, K., Wilmer, M., 2008. Prothrombinase-induced clotting time assay for determination of the anticoagulant effects of unfractionated and low-molecular-weight heparins, fondaparinux, and thrombin inhibitors. Am. J. Clin. Pathol. 130, 446–454.PubMedCrossRefGoogle Scholar
  8. Canoso, R.T., Hutton, R.A., Deykin, D., 1979. The haemostatic defect of chronic liver disease. Gastroenterology 76, 540–547.PubMedGoogle Scholar
  9. Carr, M.E., Carr, S.L., Greilich, P.E., 1996. Heparin ablates force development during platelet mediated clot retraction. Thromb. Haemost. 75, 674–678.PubMedGoogle Scholar
  10. Castro, H.C., Zingali, R.B., Albuquerque, M.G., Pujol-Luz, M., Rodrigues, C.R., 2004. Snake venom thrombin-like enzymes: from reptilase to now. Cell Mol. Life Sci. 61, 843–856.PubMedCrossRefGoogle Scholar
  11. Chattopadhyay, A., Fair, D.S., 1989. Molecular recognition in the activation of human blood coagulation factor X. J. Biol. Chem. 264, 11035–11043.PubMedGoogle Scholar
  12. Clemetson, K.J., Navdaev, A., Dörmann, D., Du, X.Y., Clemetson, J.M., 2001. Multifunctional snake C-type lectins affecting platelets. Haemostasis 31, 148–154.PubMedGoogle Scholar
  13. Collados, M.T., Fernandez, J., Paramo, J.A., Montes, R., Borbolla, J.R., Montano, L.F., Rocha, E., 1997. Purification and characterization of a variant of human prothrombin: prothrombin Segovia. Thromb. Res. 85, 465–477.PubMedCrossRefGoogle Scholar
  14. Court, E.L., 1997. Lupus anticoagulants: pathogenesis and laboratory diagnosis. Br. J. Biomed. Sci. 54, 287–298.PubMedGoogle Scholar
  15. Cunningham, M.T., Brandt, J.T., Laposata, M., Olson, J.D., 2002. Laboratory diagnosis of dysfibrinogenaemia. Arch. Pathol. Lab. Med. 126, 499–505.PubMedGoogle Scholar
  16. Denson, K.W.E., 1961. The specific assay of Prower Stuart factor and factor VII. Acta. Haematol. 25, 105–120.PubMedCrossRefGoogle Scholar
  17. Favaloro, E.J., Soltani, S., McDonald, J., Grezchnik, E., Easton, L., 2006. Activated protein C resistance: the influence of ABO-blood group, gender and age. Thromb. Res. 117, 665–670.PubMedCrossRefGoogle Scholar
  18. Fukushima, S., Tanaka, T., Sato, T., Shirakawa, Y., Asayama, K., Shirahata, A., 2002. Prothrombin levels in newborn infants by the carinactivase-1 method. Semin. Thromb. Hemost. 28, 539–544.PubMedCrossRefGoogle Scholar
  19. Funk, C., Gmur, J., Herold, R., Straub, P.W., 1971. Reptilase-R, a new reagent in blood coagulation. Br. J. Haematol. 21, 43–52.PubMedCrossRefGoogle Scholar
  20. Gempeler-Messina, Volz, K., Bühler, B., Müller, C., 2001. Protein C activators from snake venoms and their diagnostic use, in: Bon, C., Kini, M., Markland, F.S., Marsh, N.A., Rosing, J. (Eds.), International Conference on Exogenous Factors Affecting Thrombosis and Haemostasis. Haemostasis 31, S. Karger Medical and Scientific Publishers, pp. 266–272.Google Scholar
  21. Gerads, I., Tans, G., Yukelson, L.Ya, Zwaal, R.F., Rosing, J., 1992. Activation of bovine factor V by an activator purified from the venom of Naja naja oxiana. Toxicon 30, 1065–1079.PubMedCrossRefGoogle Scholar
  22. Gowda, D.C., Jackson, C.M., Hensley, P., Davidson, E.A., 1994. Factor X-activating glycoprotein of Russell’s viper venom. Polypeptide composition and characterization of the carbohydrate moieties. J. Biol. Chem. 269, 10644–10650.PubMedGoogle Scholar
  23. Graff, J., Picard-Willems, B., Harder, S., 2007. Monitoring effects of direct FXa-inhibitors with a new one-step prothrombinase-induced clotting time (PiCT) assay: comparative in vitro investigation with heparin, enoxaparin, fondaparinux and DX 9065a. Int. J. Clin. Pharmacol. Ther. 45, 237–243.PubMedGoogle Scholar
  24. Harder, S., Parisius, J., Picard-Willems, B., 2008. Monitoring direct FXa-inhibitors and fondaparinux by Prothrombinase-induced Clotting Time (PiCT): relation to FXa-activity and influence of assay modifications. Thromb Res. 123, 396–403.PubMedCrossRefGoogle Scholar
  25. Hardisty, R.M., Hutton, R.A., 1966. Platelet aggregation and the availability of platelet factor 3. Br. J. Haematol. 12, 764–776.PubMedCrossRefGoogle Scholar
  26. Harenberg, J., Giese, C., Hagedorn, A., Traeger, I., Fenyvesi, T., 2007. Determination of antithrombin-dependent factor Xa inhibitors by prothrombin-induced clotting time. Semin Thromb Hemost. 33, 503–507.PubMedCrossRefGoogle Scholar
  27. Harenberg, J., Jörg, I., Vukojevic, Y., Mikus, G., Weiss, C., 2008. Anticoagulant effects of idraparinux after termination of therapy for prevention of recurrent venous thromboembolism: observations from the van Gogh trials. Eur. J. Clin. Pharmacol. 64, 555–563.PubMedCrossRefGoogle Scholar
  28. Hoagland, L.E., Triplett, D.A., Peng, F., Barna, L., 1996. APC-resistance as measured by a textarin time assay—comparison to the APTT-based method. Thromb. Res. 83, 363–373.PubMedCrossRefGoogle Scholar
  29. Howie, P.W., Prentice, C.R.M., McNicol, G.P., 1973. A method of antithrombin estimation using plasma defibrinated with ancrod. Br. J. Haematol. 25, 101–110.PubMedCrossRefGoogle Scholar
  30. Hutton, R.A., Warrell, D.A., 1993. Action of snake venom components on the haemostatic system. Blood Rev. 7, 176–189.PubMedCrossRefGoogle Scholar
  31. Inoue, K., Morita, T., 1993. Identification of O-linked oligosaccharide chains in the activation peptides of blood coagulation factor X. Eur. J. Biochem. 218, 153–163. (Leipzig) 115, 483–487.PubMedCrossRefGoogle Scholar
  32. Jy, W.C., Horstman, L.L., Wang, F., Duncan, R.C., Ahn, Y.S., 1995. Platelet factor 3 in plasma fractions—its relation to micro-particle size and thromboses. Thromb. Res. 80, 471–482.PubMedCrossRefGoogle Scholar
  33. Kamiguti, A.S., 2005. Platelets as targets of snake venom metalloproteinases. Toxicon 45, 1041–1049PubMedCrossRefGoogle Scholar
  34. Kathiresan, S., Shiomura, J., Jang, I.K., 2002. Argatroban. J. Thromb. Thrombolysis 13, 41–47.PubMedCrossRefGoogle Scholar
  35. Kaufmann, R., Zieger, M., Tausch, S., Henklein, P., Nowak, G., 2000. Meizothrombin, an intermediate of prothrombin activation, stimulates human glioblastoma cells by interaction with PAR-1-type thrombin receptors. J. Neurosci. Res. 59, 643–648.PubMedCrossRefGoogle Scholar
  36. Keller, F.G., Ortel, T.L., Quinn-Allen, M.A., Kane, W.H., 1995. Thrombin-catalysed activation of recombinant human factor V. Biochemistry 34, 4118–4124.PubMedCrossRefGoogle Scholar
  37. Kini, R.M., 2005. The intriguing world of prothrombin activators from snake venom. Toxicon 45, 1133–1145.PubMedCrossRefGoogle Scholar
  38. Kini, R.M., 2006, Anticoagulant proteins from snake venoms: structure, function and mechanism. Biochem. J. 397, 377–387.PubMedCrossRefGoogle Scholar
  39. Kini, R.M., Rao, V.S., Joseph, J.S., 2001. Procoagulant proteins from snake venoms, in: Bon, C., Kini, M., Markland, F.S., Marsh, N.A., Rosing, J. (Eds.), International Conference on Exogenous Factors Affecting Thrombosis and Haemostasis. Haemostasis 31, S. Karger Medical and Scientific Publishers, pp. 218–224.Google Scholar
  40. Kini, R.M., Joseph, J.S., Rao, V.S., 2002. Prothrombin activators from snake venoms, in: Menez, A. (Ed.), Perspectives in Molecular Toxinology. John Wiley & Sons Ltd., Chichester, pp. 341–355.Google Scholar
  41. Kisiel, W., Canfield, W.M., 1981. Snake venom proteases that activate blood coagulation factor V, in: Lorand, L. (Ed.), Methods in Enzymology (vol. 80). Academic Press, New York, pp. 275–285.Google Scholar
  42. Klein, J.D., Walker, F.D., 1986. Purification of a Protein C activator from the venom of the Southern copperhead snake (Agkistrodon contortrix contortrix). Biochemistry 25, 4175–4178.PubMedCrossRefGoogle Scholar
  43. Knight, L.C., Romano, J.E., 2005. Functional expression of bitistatin, a disintegrin with potential use in molecular imaging of thromboembolic disease. Protein Expr. Purif. 39, 307–319.PubMedCrossRefGoogle Scholar
  44. Koh, D.C., Armugam, A., Jeyaseelan, K., 2006. Snake venom components and their applications in biomedicine. Cell Mol. Life Sci. 63, 3030–3041.PubMedCrossRefGoogle Scholar
  45. Kornalik, F., 1985. The influence of snake venom enzymes on blood coagulation. Pharmacol. Ther. 29, 353–405.PubMedCrossRefGoogle Scholar
  46. Kornalik, F., 1990. Toxins affecting blood coagulation and fibrinolysis, in: Shier, W.T., Mebs, D. (Eds.), Handbook of Toxicology. Marcel Dekker Inc., New York, pp. 683–760.Google Scholar
  47. Kornalik, F., Vorlova, Z., 1988. Ecarin test in diagnosis of dicoumarol therapy, liver diseases and DIC. Folia Haematol. (Leipzig) 115, 483–487.Google Scholar
  48. Kumar, R., Beguin, S., Hemker, H.C., 1994. The influence of fibrinogen and fibrin on thrombin generation—evidence for feedback activation of the clotting system by clot bound thrombin. Thromb. Haemost. 72, 713–721.PubMedGoogle Scholar
  49. Lange, U., Nowak, G., Bucha, E., 2003. Ecarin chromogenic assay—a new method for quantitative determination of direct thrombin inhibitors like hirudin. Pathophysiol. Haemost. Thromb. 33, 184–191.PubMedCrossRefGoogle Scholar
  50. Latallo, Z., Teisseyre, E., 1971. Evaluation of reptilase-R and thrombin clotting time in the presence of fibrinogen degradation products and heparin. Scand. J. Haematol. 1971; 261–266.Google Scholar
  51. Lu, Q., Clemetson, J.M., Clemetson, K.J., 2005. Snake venoms and hemostasis. J. Thromb. Haemost. 3, 1791–1799.PubMedCrossRefGoogle Scholar
  52. Markland, F.S., Jr., 1997. Snake venoms. Drugs 54(Suppl 3), 1–10.PubMedCrossRefGoogle Scholar
  53. Markland, F.S., 1998. Snake venoms and the hemostatic system. Toxicon 36, 1749–1800.PubMedCrossRefGoogle Scholar
  54. Marsh, N.A., 1994. Snake venoms affecting the haemostatic mechanism—a consideration of their mechanisms, practical applications and biological significance. Blood Coagul. Fibrinolysis 5, 399–410.PubMedGoogle Scholar
  55. Marsh, N., 2001. Diagnostic uses of snake venom, in: Bon, C., Kini, M., Markland, F.S., Marsh, N.A., Rosing, J. (Eds.), International Conference on Exogenous Factors Affecting Thrombosis and Haemostasis. Haemostasis 31, S. Karger Medical and Scientific Publishers, pp. 211–217.Google Scholar
  56. Marsh, N.A., Fyffe, T.L., 1996. Practical applications of snake venom toxins in haemostasis. Boll. Soc. Ital., Biol. Sper. 72, 263–278.Google Scholar
  57. Marsh, N., Williams, V., 2005. Practical applications of snake venom toxins in haemostasis. Toxicon 45, 1171–1181.PubMedCrossRefGoogle Scholar
  58. Matsui, T., Fujimura, Y., Titani, K., 2000. Snake venom proteases affecting hemostasis and thrombosis. Biochim. Biophys. Acta 1477, 146–156.PubMedCrossRefGoogle Scholar
  59. Matsui, T., Hamako, J., 2005. Structure and function of snake venom toxins interacting with human von Willebrand factor. Toxicon 45, 1075–1087.PubMedCrossRefGoogle Scholar
  60. Meier, J., Stocker, K., 1991. Snake venom protein C activators, in: Tu, A.T. (Ed.), Handbook of Natural Toxins. Marcel Dekker Inc., New York-Basel-Hong Kong, pp. 265–280.Google Scholar
  61. Meier, J., 1998. Proteinases activating protein C, in: Bailey, G.S. (Ed.), Enzymes from Snake Venom. Alaken Inc., Fort Collins, CO, pp. 253–285.Google Scholar
  62. Miura, S., Nishida, S., Makita, K., Sakurai, Y., Shimoyama, T., Sugimoto, M., Yoshioka, A., Ishii, K., Kito, M., Kobayashi, T., Fujimura, Y., 1996. Inhibition assay for the binding of biotinylated von Willebrand factor to platelet-bound microtiter wells in the presence of ristocetin or botrocetin. Anal., Biochem. 236, 215–220.CrossRefGoogle Scholar
  63. Moore, G.W., 2007. Combining Taipan snake venom time/Ecarin time screening with the mixing studies of conventional assays increases detection rates of lupus anticoagulants in orally anticoagulated patients. Thromb. J. 5, 12–16PubMedCrossRefGoogle Scholar
  64. Moore, G.W., Savidge, G.F., 2004. Heterogeneity of Russell’s viper venom affects the sensitivity of the dilute Russell’s viper venom time to lupus anticoagulants. Blood Coagul. Fibrinolysis 15, 279–82PubMedCrossRefGoogle Scholar
  65. Moore, G.W., Smith, M.P., Savidge, G.F., 2003. The Ecarin time is an improved confirmatory test for the Taipan snake venom time in warfarinised patients with lupus anticoagulants. Blood Coagul. Fibrinolysis 14, 307–312.PubMedGoogle Scholar
  66. Morita, T., 1998. Proteases which activate factor X, in: Bailey, G.S. (Ed.), Enzymes from Snake Venom. Alaken Inc., Fort Collins, CO, pp. 179–208.Google Scholar
  67. Moser, M., Ruef, J., Peter, K., Kohler, B., Gulba, D.C., Paterna, N., Nordt, T., Kubler, W., Bode, C., 2001. Ecarin clotting time but not aPTT correlates with PEG-hirudin plasma activity. J. Thromb. Thrombolysis 12, 165–169.PubMedCrossRefGoogle Scholar
  68. Nowak, G., 2003/2004. The ecarin clotting time, a universal method to quantify direct thrombin inhibitors. Pathophysiol. Haemost. Thromb. 33, 173–183.PubMedCrossRefGoogle Scholar
  69. Nowak, G., Bucha, E., 1996. Quantitative determination of hirudin in blood and body fluids. Semin. Thromb. Hemost. 22, 197–202.PubMedCrossRefGoogle Scholar
  70. Novoa, E., Seegers, W.H., 1980. Mechanisms of α-thrombin and β- thrombin-E formation: use of ecarin for isolation of meizothrombin 1. Thromb. Res. 18, 657–668.PubMedCrossRefGoogle Scholar
  71. Parmar, K., Lefkou, E., Doughty, H., Connor, P., Hunt, B.J., 2009. The utility of the Taipan snake venom assay in assessing lupus anticoagulant status in individuals receiving or not receiving an oral vitamin K antagonist. Blood Coagul. Fibrinolysis 20, 271–275.PubMedCrossRefGoogle Scholar
  72. St. Pierre, L., Masci, P.P., Filippovich, I., Sorokina, N., Marsh, N., Miller, D.J., Lavin, M.F., 2005. Comparative analysis of prothrombin activators from the venom of Australian elapids. Mol. Biol. Evol. 22, 1853–1864.PubMedCrossRefGoogle Scholar
  73. Pirkle, H., 1998. Thrombin-like enzymes from snake venoms: an updated inventory. Scientific and standardization committee’s registry of exogenous hemostatic factors. Thromb. Haemost. 79, 675–683.Google Scholar
  74. Quehenberger, P., Handler, S., Mannhalter, C., Pabinger-Fasching, I., Speiser, W., 2000. Evaluation of a highly specific functional test for the detection of factor V Leiden. Int. J. Clin. Lab. Res. 30, 113–117.CrossRefGoogle Scholar
  75. Quick, A.J., 1971. Thromboplastin generation: effect of the Bell-Alton reagent and Russell’s viper venom on prothrombin consumption. Am. J. Clin. Pathol. 55, 555–560.PubMedGoogle Scholar
  76. Rabinowitz, I., Tuley, E.A., Mancuso, D.J., Randi, A.M., Firkin, B.G., Howard, M., Sadler, J.E., 1992. Von Willebrand disease type B: a missense mutation selectively abolishes ristocetin-induced von Willebrand factor binding to platelet glycoprotein Ib. Proc. Natl. Acad. Sci. U.S.A. 89, 9846–9849.PubMedCrossRefGoogle Scholar
  77. Ranby, M., Norrman, B., Wallen, P., 1982. A sensitive assay for tissue plasminogen activator. Thromb. Res. 27, 743–749.PubMedCrossRefGoogle Scholar
  78. Read, M.S., Smith, S.V., Lamb, M.A., Brinkhous, K.M., 1989. Role of botrocetin in platelet agglutination: formation of an activated complex of botrocetin and von Willebrand factor. Blood 74, 1031–1035.PubMedGoogle Scholar
  79. Robert, A., Eschwege, V., Hameg, H., Drouet, L., Aillaud, M.F., 1996. Anticoagulant response to Agkistrodon contortrix venom (ACVtest): a new global test to screen for defects in the anticoagulant protein C pathway. Thromb. Haemost. 75, 562–566.PubMedGoogle Scholar
  80. Rooney, A.M., McNally, T., Mackie, I.J., Machin, S.J., 1994. The taipan snake venom time: a new test for lupus anticoagulant. J. Clin. Pathol. 47, 497–501.PubMedCrossRefGoogle Scholar
  81. Rosing, J., Govers-Riemslag, J.W.P., Yukelson, L., Tans, G., 2001. Factor V activation and inactivation by venom proteases, in: Bon, C., Kini, M., Markland, F.S., Marsh, N.A., Rosing, J. (Eds.), International Conference on Exogenous Factors Affecting Thrombosis and Haemostasis. Haemostasis 31, S. Karger Medical and Scientific Publishers, pp. 241–246.Google Scholar
  82. Rosing, J., Tans, G., 1988. Meizothrombin, a major product of factor Xa-catalysed prothrombin activation. Thromb. Haemost. 60, 355–360.PubMedGoogle Scholar
  83. Rosing, J., Tans, G., 1992. Structural and functional properties of snake venom prothrombin activators. Toxicon 30, 1515–1527.PubMedCrossRefGoogle Scholar
  84. Sakuragawa, N., Takahashi, K., Hoshiyama, M., Jimbo, C., Matsuoka, M., Onishi, Y., 1975. Significance of a prothrombin assay method using Echis carinatus venom for diagnostic information in disseminated intravascular coagulation syndrome. Thromb. Res. 7, 643–653.PubMedCrossRefGoogle Scholar
  85. Sarig, G., Aberbach, I., Schliamser, L., Blumenfeld, Z., Brenner, B., 2006. Evaluation of ProC Global assay in women with a history of venous thromboembolism on hormonal therapy. Thromb. Haemost. 96, 578–583.PubMedGoogle Scholar
  86. Schöni, R. 2005. The use of snake venom-derived compounds for new functional diagnostic test kits in the field of haemostasis, in: Kini, R.M., Marsh, N., Markland, F.S., Broady, K.W. (Eds.), Proceedings of the Third International Conference, EFATH 2005. Pathophysiol. Haemost. Thromb. 34, S. Karger Medical and Scientific Publishers, pp. 234–240.Google Scholar
  87. Sillero, P.L., Fernández de Velasco, J., Loscertales, J., Espinoza, J., Soto, C., Tomás, J.F., 2001. ProC global: an automated screening test for factor V Leiden and prothrombin mutation 20210 G to A detection. Thromb. Res. 101, 215–216.PubMedCrossRefGoogle Scholar
  88. Stevens, W.K., Cote, H.C.F., MacGillivray, R.T.A., Nesheim, M.E., 1996. Calcium ion modulation of meizothrombin autolysis at Arg55–Asp56 and catalytic activity. J. Biol. Chem. 271, 8062–8067.PubMedCrossRefGoogle Scholar
  89. Stocker, K., 1986. Use of snake venom proteins in the diagnosis and therapy of haemostatic disorders, in: Kornalik, K., Mebs, D. (Eds.), 7th European Symposium on Animal, Plant and Microbial Toxins. Prague, pp. 9–40.Google Scholar
  90. Stocker, K., 1998. Research, diagnostic and medicinal uses of snake venom enzymes, in: Bailey, G.S. (Ed.), Enzymes from Snake Venom. Alaken Inc., Fort Collins, CO, pp. 705–736.Google Scholar
  91. Stocker, K., Fischer, H., Meier, J., Brogli, M., Svendsen, L., 1986. Protein C activators in snake venoms. Behring Inst. Mitt. 79, 37–47.PubMedGoogle Scholar
  92. Stocker, K., Fischer, H., Meier, J., Brogli, M., Svendsen, L., 1987. Characterization of the protein C activator Protac from the venom of the southern copperhead (Agkistrodon contortrix) snake. Toxicon 25, 239–252.PubMedCrossRefGoogle Scholar
  93. Stocker, K., 1990. Snake venom proteins affecting hemostasis and fibrinolysis, in: Stocker, K. (Ed.), Medical Use of Snake Venom Proteins. CRC Press, Inc., Boca Raton, pp. 97–160.Google Scholar
  94. Suzuki, K., Nishioka, J., 1988. Plasma protein S activity measured using Protac, a snake venom derived activator of protein C. Thromb. Res. 49, 241–251.PubMedCrossRefGoogle Scholar
  95. Takeya, H., Nishida, S., Miyata, T., Kawada, S., Saisaka, Y., Morita, T., Iwanaga, S., 1992. 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. 267, 14109–14117.PubMedGoogle Scholar
  96. Tans, G., Rosing, J., 2001 Snake venom activators of factor X: an overview, in: Bon, C., Kini, M., Markland, F.S., Marsh, N.A., Rosing, J. (Eds.), International Conference on Exogenous Factors Affecting Thrombosis and Haemostasis. Haemostasis 31, S. Karger Medical and Scientific Publishers, pp. 225–233.Google Scholar
  97. Thiagarajan, P., Pengo, V., Shapiro, S.S., 1986. The use of dilute Russell viper venom time for the diagnosis of lupus coagulants. Blood 68, 869–874.PubMedGoogle Scholar
  98. Tokunaga, F., Nagasawa, K., Tamura, S., Miyata, T., Iwanaga, S., Kisiel, W., 1988. The factor V-activating enzyme (RVV-V) from Russell’s viper venom. Identification of isoproteins RVV-V alpha, -V beta, and -V gamma and their complete amino acid sequences. J. Biol. Chem. 263, 17471–17481.PubMedGoogle Scholar
  99. Torbet, J., 1987. Fibrin assembly after fibrinopeptide A release in model systems and human plasma studied with magnetic birefringence. Biochem. J. 15, 633–637.Google Scholar
  100. Toulon, P., Halbmeyer, W.M., Hafner, G., Schmitt, Y., Randgard, B., Odpadlik, M., van den Eynden, C., Wagner, C., 2000. Screening for abnormalities of the protein C anticoagulant pathway using the ProC Global assay. Results of a European multicenter evaluation. Blood Coagul. Fibrinolysis 11, 447–454.Google Scholar
  101. Triplett, D.A., Stocker, K., Unger, G.A., Barna, L.K., 1993. The textarin/ecarin ratio: a confirmatory test for lupus anticoagulants. Thromb. Haemost. 70, 925–931.PubMedGoogle Scholar
  102. Van Cott, E.M., Smith, E.Y., Galanakis, D.K., 2002. Elevated fibrinogen in an acute phase reaction prolongs the reptilase time but typically not the thrombin time. Am. J. Clin. Path. 118, 263–268.PubMedCrossRefGoogle Scholar
  103. Weinger, R.S., Rudy, C., Moake, J.L., Olson, J.D., Cimo, P.L.,1980. Prothrombin Houston: a dysprothrombin identifiable by crossed immunoelectrofocussing and abnormal Echis carinatus venom activation. Blood 55, 811–815.PubMedGoogle Scholar
  104. Wijeyewickrema, L., Berndt, M.C., Andrews, R.K., 2005. Snake venom probes of platelet adhesion receptors and their ligands. Toxicon 45, 1051–61.PubMedCrossRefGoogle Scholar
  105. Williams, S.B., McKeown, L.P., Krutzsch, H., Hansmann, K., Gralnick, H.R., 1994. Purification and characterization of human platelet von Willebrand factor. Br. J. Haematol. 88, 582–591.PubMedCrossRefGoogle Scholar
  106. Wilmer, M., Stocker, C., Bühler, B., Conell, B., Calatzis, A., 2004. Improved distinction of factor V wild-type and factor V Leiden using a novel prothrombin-based activated protein C resistance assay. Am. J. Clin. Pathol. 122, 836–842.PubMedCrossRefGoogle Scholar
  107. Yamada, D., Morita, T., 1997. Purification and characterization of a Ca2+-dependent prothrombin activator, multactivase, from the venom of Echis multisquamatus. J. Biochem. 122, 991–997.PubMedCrossRefGoogle Scholar
  108. Yamada, D., Morita, T., 1999. CA-1 method, a novel assay for quantification of normal prothrombin using a Ca2+-dependent prothrombin activator, carinactivase-1. Thromb. Res. 94, 221–226.PubMedCrossRefGoogle Scholar
  109. Yamada, D., Sekiya, F., Morita, T., 1996. Isolation and characterization of carinactivase, a novel prothrombin activator in Echis carinatus venom with a unique catalytic mechanism. J. Biol. Chem. 271, 5200–5207.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Swiss Tropical and Public Health Institute, Medical Parasitology and Infection BiologySocinstrasse 57Switzerland
  2. 2.August Lenz Foundation at the Institute for Prevention of Cardiovascular DiseasesUniversity of MunichMunichGermany
  3. 3.Department DXSCRoche Diagnostics LtdRotkreuzSwitzerland

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