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Defibrinogenating Enzymes

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Summary

The venoms from 3 snakes have been shown to induce defibrinogenation: ancrod from the venom of Calloselasma rhodostoma (formerly known as Agkistrodon rhodostoma), batroxobin from the venom of Bothrops atrox moojeni, and crotalase from the venom of Crotalus adamanteus. The purified fractions of ancrod, batroxobin, and crotalase possess coagulant, proteolytic and esterolytic properties, although their primary mechanism of action is a proteolytic effect on circulating fibrinogen. Ancrod cleaves only the A-fibrinopeptides, but not the B-fibrinopeptides, from fibrinogen; this contrasts with thrombin, batroxobin and crotalase, which cleave both fibrinopeptides A and B.

Within minutes of administration of ancrod or batroxobin, there is a significant reduction in plasma fibrinogen levels, and these remain exceedingly low with repeated administration (once or twice daily). The rapid fall in plasma fibrinogen levels is accompanied by a slightly delayed but marked rise in the level of fibrinogen-fibrin degradation products. Plasminogen levels are decreased and blood viscosity is reduced, but formed elements in the circulating blood remain unaltered.

Ancrod and batroxobin have been investigated in patients with stroke, deep-vein thrombosis, myocardial infarction, peripheral arterial thrombosis, priapism, and sickle-cell crisis; crotalase has not been administered to humans. However, results have been difficult to interpret, and additional well designed trials are needed to better define the optimum role of ancrod and batroxobin in the management of these conditions. Overall, treatment is well tolerated and serious adverse events are infrequent.

In the coagulation laboratory, ancrod, batroxobin and crotalase may be used as reagents to perform coagulation studies on specimens of blood that contain heparin. These venom fractions can be substituted for thrombin in performing the thrombin time and in removing fibrinogen from plasma for accurate determination of fibrinogen-fibrin degradation products.

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References

  1. Tu AT. Blood coagulation. In: Venoms: chemicals and molecular biology. Chapter 21. New York: J Wiley & Sons, 1977: 329–59

    Google Scholar 

  2. Minton SA, Minton MR. Grant reptiles. New York: C. Scribner’s Sons, 1973

    Google Scholar 

  3. Minton SA. Venom diseases. Springfield IL: CC Thomas, 1974

    Google Scholar 

  4. Fontana F. Treatise on the venom of the viper. Vol. I-409, Vol. II-395; London: J Murray, 1787

    Google Scholar 

  5. Mitchell SW, Reichert ET. Researches upon the venoms of poisonous serpents. Smithsonian contributions to knowledge. Washington DC: Smithsonian Institution, 1886; 26: 1–86

  6. Mitchell SW, Stewart AH. A contribution to the study of the effect of the venom of Crotalus adamanteus upon the blood of man and animals. Memoris Natl Acad Sci 1898; 8: 3–14

    Google Scholar 

  7. Taylor J, Mallick SMK, Ahuja ML. The coagulant action on blood of Daboia and Echis venoms and its neutralization. Indian J Med Res 1935; 23: 131–40

    CAS  Google Scholar 

  8. Eagle H. The coagulation of blood by snake venoms and its physiologic significance. J Exp Med 1937; 65: 613–39

    PubMed  CAS  Google Scholar 

  9. Jimenez-Porras JM. Biochemistry of snake venoms. Clin Toxicol 1970; 3: 389–431

    PubMed  CAS  Google Scholar 

  10. Minton SA, Minton MR. Venomous reptiles. London: George Allen, 1971

    Google Scholar 

  11. Devi A. The protein and nonprotein constituents of snake venoms. In: Bucherl W, Buckley EE, Deulofeu V, editors. Venomous animals and their venoms. Vol. 1. New York: Academic Press, 1968: 119

    Google Scholar 

  12. Sarkar NK, Devi A. Enzymes in snake venoms. In: Bucherl W, Buckley EE, Deulofeu V, editors. Venomous animals and their venoms. Vol. 1. New York: Academic Press, 1968: 167

    Google Scholar 

  13. Lee CY. Chemistry and pharmacology of polypeptide toxins in snake venoms. Ann Rev Pharmacol 1972; 12: 265–86

    PubMed  CAS  Google Scholar 

  14. Rosenfeld G, Nahas L, Kelen EMA. Coagulant proteolytic and hemolytic properties of some snake venoms. In: Bucherl W, Buckley EE, Deulofeu V, editors. Venomous animals and their venoms. Vol. 1. New York: Academic Press, 1968: 229

    Google Scholar 

  15. Marsh N, Whaler B. The effects of snake venoms on the cardiovascular and hemostatic mechanism. Int J Biochem 1978; 9: 217–20

    PubMed  CAS  Google Scholar 

  16. Stocker K. Defibrinogenation with thrombin-like snake venom enzymes in fibrinolytics and anti-fibrinolytics. In: Markwardt F, editor. Handbook of experimental pharmacology. Vol. 46. Berlin: Springer-Verlag, 1978: 451–84

    Google Scholar 

  17. Denson KWE, Borrett R, Biggs R. The specific assay of prothrombin using the Taipan snake venom. Br J Haematol 1971; 21: 219–26

    PubMed  CAS  Google Scholar 

  18. Reid HA, Chan KE, Thean PC. Prolonged coagulation defect (defibrination syndrome) in Malayan viper bite. Lancet 1963; 1: 621–6

    PubMed  CAS  Google Scholar 

  19. Reid HA, Chan KE. The paradox in therapeutic defibrination. Lancet 1968; I: 485–6

    Google Scholar 

  20. Chan KE. The comparison of antithrombotic action on the thrombin-like fraction of Malayan pit-viper venom and heparin. Cardiovasc Res 1969; 3: 171–8

    PubMed  CAS  Google Scholar 

  21. Ouyang C, Hong LS, Teng ChM. Purification and properties of the thrombin-like principle of Agkistrodon acutus venom and its comparison with bovine thrombin. Thromb Diath Haemorrh 1971; 26: 224–34

    PubMed  CAS  Google Scholar 

  22. Denson KWE, Russel FE, Almagro D, et al. Characterization of some snake venoms. Toxicon 1972; 10: 557–62

    PubMed  CAS  Google Scholar 

  23. Jansky B. The relation between the proteolytic and blood clotting activity of snake venoms. Arch Biochem 1950; 28: 139–40

    Google Scholar 

  24. Stocker K, Christ W, Leloup P. Characterization of the venoms of various Bothrops species by immunoelectrophoresis and reaction with fibrinogen agarose. Toxicon 1974; 12: 415–7

    PubMed  CAS  Google Scholar 

  25. Markland FS, Damus PS. Purification and properties of a thrombin-like enzyme from the venom of Crotalus (eastern diamondback rattlesnake). J Biol Chem 1971; 246: 6460–73

    PubMed  CAS  Google Scholar 

  26. Denson KWE. Coagulation and anticoagulant action of snake venoms. Toxicon 1969; 7: 5–11

    PubMed  CAS  Google Scholar 

  27. Holleman WH, Weiss LJ. The thrombin-like enzyme from Bothrops atrox snake venom. Properties of the enzyme purified by affinity chromatography on p-aminobenzamidine-substituted agarose. J Biol Chem 1976; 251: 1663–9

    PubMed  CAS  Google Scholar 

  28. Arocha-Pinango CL, Layrisse M. Fibrinolysis produced by contact with a caterpillar. Lancet 1969; 1:810–2

    PubMed  CAS  Google Scholar 

  29. Arocha-Pinango CL, Marsh NA, Robinson D. A fibrinolytic agent from Saturnid caterpillar-partial purification and characterization. Thromb Diath Haemorrh 1973; 29: 135–42

    PubMed  CAS  Google Scholar 

  30. Cartwright T. The plasminogen activator of vampire bat saliva. Blood 1974; 43: 317–26

    PubMed  CAS  Google Scholar 

  31. Frisch EP. Clinical review of brinase, a protease from Aspergillus oryzae. Folia Haematol (Leipz) 1974; 101: 63–82

    CAS  Google Scholar 

  32. Patterson RA. Physiological action of scorpion venom. Am J Trop Med Hyg 1960; 9: 410–4

    PubMed  CAS  Google Scholar 

  33. Soong BCF, Miller SP. Defibrination and the hypercoagulable state: a model using papain in rabbits. Am J Physiol 1972; 222: 1113–20

    PubMed  CAS  Google Scholar 

  34. Bell WR. Thrombolytic therapy: a comparison between urokinase and streptokinase. Semin Thromb Hemost 1975; 2: 1–13

    PubMed  CAS  Google Scholar 

  35. Ewart MR, Hatton MWC, Basford JM, et al. The proteolytic action of Arvin on human fibrinogen. Biochem J 1970; 118: 603–9

    PubMed  CAS  Google Scholar 

  36. Holleman WH, Coen LJ. Characterization of peptides released from human fibrinogen by Arvin. Biochem Biophys Acta 1970; 200: 587–9

    PubMed  CAS  Google Scholar 

  37. Stocker K, Straub PW. Rapid detection of fibrinopeptides by bidimensional paper electrophoresis. Thromb Diath Haemorrh 1970; 24: 248–55

    PubMed  CAS  Google Scholar 

  38. Kwaan HC, Barlow GH. The mechanism of action of Arvin and reptilase. Thromb Diath Haemorrh 1971; 47 (Suppl.): 361–9

    Google Scholar 

  39. Caprini JA, Kwaan HC, Zuckerman L. Thromboelastographic patterns of ancrod and thrombin fibrin formation and dissolution. Thromb Res 1974; 4: 199–217

    PubMed  CAS  Google Scholar 

  40. Markland Jr FS. Snake venoms. Drugs 1997; 54 Suppl. 3: 1–10

    Google Scholar 

  41. Hatton MWC. Studies on the coagulant enzyme from Agkistrodon rhodostoma venom. Biochem J 1973; 131: 799–807

    PubMed  CAS  Google Scholar 

  42. Stocker K, Egberg N. Reptilase as defibrinogenating agent. Thromb Diath Haemorrh 1973; 1: 361–70

    Google Scholar 

  43. Collins JP, Jones JG. Identification of serine and histidine as essential amino-acid residues in the coagulant enzyme ancrod. Eur J Biochem 1974; 42: 81–7

    PubMed  CAS  Google Scholar 

  44. Karpatkin S, Karpatkin M. Inhibition of the enzymatic activity of thrombin by concanavalin A. Biochem Biophys Res Commun 1974; 57: 1111–8

    PubMed  CAS  Google Scholar 

  45. Okamoto S, Hijikata A, Kinjo K, et al. A novel series of synthetic thrombin-inhibitors having extremely potent and highly selective action. Kobe J Med Sci 1975; 21: 43–51

    PubMed  CAS  Google Scholar 

  46. Markwardt F, Landmann H, Walsmann P. Comparative studies on the inhibition of trypsin, plasmin and thrombin, by derivatives of benylamine and benzamidine. Eur J Biochem 1968; 6: 502–6

    PubMed  CAS  Google Scholar 

  47. Exner T, Koppel JL. Observations concerning the substrate specificity of Arvin. Biochem Biophys Acta 1972; 258: 825–9

    PubMed  CAS  Google Scholar 

  48. Egberg N, Nordstrom S. Effects of reptilase induced intravascular coagulation in dogs. Acta Physiol Scand 1970; 79: 493–505

    PubMed  CAS  Google Scholar 

  49. Larrieu MJ, Rigollot C, Marder VJ. Comparative effects of fibrinogen degradation fragments D and E on coagulation. Br J Haematol 1972; 22: 719–33

    PubMed  CAS  Google Scholar 

  50. Lewis LJ, Martin DL, Buckner S, et al. Studies on type specific immunity to the whole venom and a fraction of Agkistrodon rhodostoma. Res Commun Chem Pathol Pharmacol 1971; 2: 649–56

    PubMed  CAS  Google Scholar 

  51. Barlow GH, Lewis J, Finley R, et al. Immunochemical identification of ancrod (A38414) and reptilase (defibrase). Thromb Res 1973; 2: 17–22

    CAS  Google Scholar 

  52. Sharp AA, Warren B A, Paxton AM, et al. Anticoagulant therapy with a purified fraction from Malayan pit viper venom. Lancet 1968; 1: 493–9

    PubMed  CAS  Google Scholar 

  53. Lorand L, Hsia DY. Inheritance of factor VIII. Am J Hum Gen 1970; 22: 598

    CAS  Google Scholar 

  54. Krause W, Zimmerman P. Quantative elektronenmik-reskepische Untersuchungen zur Fibrinstrukter bei Dysfibrinogenamie. Klin Wochenschr 1972; 50: 557–61

    PubMed  CAS  Google Scholar 

  55. Kwaan HC, Grument G. Potentiation of plasminogen activation by ancrod and reptilase. Fed Proc 1973; 32: 427

    Google Scholar 

  56. Carr M, Shen LLL. Physical studies of gels of fibrin and ancrod fibrin. Fed Proc 1975; 34: 354

    Google Scholar 

  57. Markland FS, Pirkle H. Biological activities and biochemical properties of thrombin-like enzymes from snake venoms. In: Lundblad RL, Fenton JW, Mann KG, editors. Chemistry and biology of thrombin. Michigan: Ann Arbor Science Publishing, 1977: 71–89

    Google Scholar 

  58. Pizzo SV, Schwartz ML, Hill RL, et al. Mechanism of ancrod anticoagulation. A direct proteolytic effect of fibrin. J Clin Invest 1972; 51: 2841–50

    PubMed  CAS  Google Scholar 

  59. Markland FS, Pirkle H. Thrombin-like enzyme from the venom of Crotalus adamanteus. Thromb Res 1977; 10: 487–94

    PubMed  CAS  Google Scholar 

  60. Barlow GH, Holleman WH, Lorand L. The action of Arvin on fibrin stabilizing factor (factor XIII). Res Commun Chem Pathol Pharmacol 1970; 1: 39–42

    PubMed  CAS  Google Scholar 

  61. Bell WR, Bolton G, Pitney WR. The effect of Arvin on blood coagulation factors. Br J Haematol 1968; 15: 589–602

    PubMed  CAS  Google Scholar 

  62. Bell WR, Shapiro SS, Martinex J, et al. The effects of ancrod the coagulating enzyme from the venom of Malayan pit viper, A. rhodostoma, on prothrombin and fibrinogen metabolism and fibrinopeptide-A release in man. J Lab Clin Med 1978; 91: 592–604

    PubMed  CAS  Google Scholar 

  63. Pirkle H, Markland FS, Theodor I. Thrombin-like enzymes of snake venoms: actions on prothrombin. Thromb Res 1976; 8: 619–27

    PubMed  CAS  Google Scholar 

  64. Pitney WR, Bell WR, Bolton G. Blood fibrinolytic activity during Arvin therapy. Br J Haematol 1969; 16: 165–71

    PubMed  CAS  Google Scholar 

  65. Aronson DL. Comparison of the actions of thrombin and the thrombin-like venom enzymes ancrod and batroxobin. Thromb Haemost 1976; 36: 9–13

    PubMed  CAS  Google Scholar 

  66. Bell WR. Defibrinogenation with Arvin in thrombotic disorders. In: Sherry S, Scriabine A, editors. Platelets and thrombosis. Baltimore: University Park Press, 1974: 275–89

    Google Scholar 

  67. Bell WR, Pitney WR. The concept of therapeutic defibrination in the treatment of thrombotic disease. Lancet 1968; 1: 490–3

    PubMed  CAS  Google Scholar 

  68. Bell WR, Regoeczi E. Isotopic studies of therapeutic anticoagulation with a coagulating enzyme. J Clin Invest 1970; 49: 1872–9

    PubMed  CAS  Google Scholar 

  69. Regoeczi E, Bell WR. In vivo behaviour of the coagulant enzyme from Agkistrodon rhodostoma venom: studies using I-125 Arvin. Br J Haematol 1969; 16: 573–87

    PubMed  CAS  Google Scholar 

  70. Alving BM, Bell WR, Evatt B. Fibrinogen synthesis in rabbits: effects of altered levels of circulating fibrinogen. Am J Physiol 1977; 232: H478–84

    PubMed  CAS  Google Scholar 

  71. Alving BM, Evatt B, Bell WR. Stimulation of fibrinogen synthesis by thrombin in rabbits with ancrod-induced difibrinogenemia. Am J Physiol 1977; 223: H562–7

    Google Scholar 

  72. Kessler CM, Bell WR. Effects of purified homologous thrombin and fibrinogen degradation products on rate of fibrinogen synthesis in rabbits. Clin Res 1977; 25: 477

    Google Scholar 

  73. Bajwa SS, Markland FS. Defibrinogenation studies with crotalase — possible clinical applications. Proc West Pharmacol Soc 1978; 21: 461–9

    PubMed  CAS  Google Scholar 

  74. Martin DL, Knollman G. Kontrolle der fibrinogenbestim-mung unter defibrinierender behandlung. In: Martin M, Schoop W, editors. Aktuelle Probleme in der Angiologie: Defibrinierung mit thrombinahnlichen Schlangengiftenzymen. Vol. 26. Stuttgart: Hans Huber Verlag, 1975: 166

    Google Scholar 

  75. Ahlgren T, Berghem L, Lagergren H, et al. Pharocytic and catabolic function of the RES in dogs subjected to defibrase defibrinogenation. Thromb Res 1976; 8: 819–28

    PubMed  CAS  Google Scholar 

  76. Regoeczi E, Gergely J, McFarlane AS. In vivo effects of Agkistrodon rhodostoma venom. Studies with fibrinogen. 1. J Clin Invest 1966; 45: 1202–12

    PubMed  CAS  Google Scholar 

  77. Regoeczi E. On the dual action of Agkistrodon rhodostoma venom on fibrinogen. Tropenmed Parasitol 1966; 17: 144–54

    Google Scholar 

  78. McKillop CE, Edgar W, Forbes CD, et al. Possible pathway for formation of fibrin degradation products during ancrod therapy. Nature 1975; 255: 638–40

    PubMed  CAS  Google Scholar 

  79. Pizzo SV, Schwartz ML, Hill RL, et al. Fibrin destruction by Arvin. The mechanism of Arvin anticoagulation [abstract]. Clin Res 1972; 20: 46

    Google Scholar 

  80. Harder AJ, Straub PW. In vitro and in vivo induction of cryofibrinogen and «paracoagulation’ by reptilase. Thromb Diath Haemorrh 1972; 27: 337–48

    PubMed  CAS  Google Scholar 

  81. Kwaan HC. Current status of ‘ancrod’ and ‘reptilase’ [abstract]. Int Soc Thromb Haemost 1972; 34: 50

    Google Scholar 

  82. Kwaan HC. Use of defibrinating agents ancrod and Reptilase in the treatment of thromboembolism. Thromb Diath Haemorrh 1973; 54 (Suppl.): 377

    Google Scholar 

  83. Egberg N. Coagulation studies in patients treated with defibrase. Acta Med Scand 1973; 194: 291–302

    PubMed  CAS  Google Scholar 

  84. Collen D, Vermylen J. Metabolism of iodine-labelled plasminogen during streptokinase and reptilase in man. Thromb Res 1973; 2: 239–49

    Google Scholar 

  85. Bell WR. Defibrinogenation with Arvin. In: Brinkhous KM, Hinnom S, editors. Thrombosis: mechanisms and control. Stuttgart: Verlag, 1973: Suppl. I: 371–5

    Google Scholar 

  86. Ehrly AM. Influence of Arwin on the flow properties of blood. Biorheology 1973; 10: 453–6

    PubMed  CAS  Google Scholar 

  87. Rodriguez-Erdmann F, Carpenter CB, Galvanek EG. Experimental dysfibrinogenemia. In vivo studies with Arvin. Blood 1971; 37: 664–74

    PubMed  CAS  Google Scholar 

  88. Asbeck F, van de Loo J. Fibrinogen-fibrin-derivative unter Defibrasebehandlung. In: Martin M, Schoop W, editors. Aktuelle Probleme in der Angiologie: Defibrinierung mit thrombinahnlichen Schlangengiftenzymen. Vol. 26. Stuttgart: Hans Huber Verlag, 1975: 79

    Google Scholar 

  89. Asbeck F, Lechler E, Martin M, et al. Derivatives of fibrinogen and fibrin during defibrinase therapy. Haemostasis 1974; 3: 340–7

    PubMed  CAS  Google Scholar 

  90. Prentice CRM, McKillop CA, Edgar W, et al. Soluble complexes production during defibrination with ancrod infusion [abstract]. Symposium Thrombin-Like Enzymes, Trier, 1975

  91. Olsson P, Blomback M, Egberg N, et al. Studies on the bleeding tendency and on the possibility of surgery in states of reptilase-induced defibrinogenation. Thromb Diath Haemorrh 1971; 47 Suppl.: 398

    Google Scholar 

  92. Egberg N. Experimental and clinical studies on the thrombin-like enzyme from the venom of Bothrops atrox. On the primary structure of fragment E. Acta Physiol Scand 1973; 400 Suppl.: 7–47

    Google Scholar 

  93. Straub PW, Harder A. Verhalten von I125-fibrinogen bei therapeutischer Defibrinierung mit hochgeneinigter Reptilase (Defibrase). Schweiz Med Wochenschr 1971; 101: 1802–4

    PubMed  CAS  Google Scholar 

  94. Olsson P, Ljungquist A, Goeransson L. Vein graft surgery in Defibrase defibrinogenated dogs. Thromb Res 1973; 3: 161

    Google Scholar 

  95. Bell WR. Further experience in the treatment of thrombotic disorders by therapeutic defibrination. QJ Med 1968; 37: 658

    Google Scholar 

  96. Prentice CR, Turpie AG, Hassanein AA, et al. Changes in platelet behaviour during Arwin therapy. Lancet 1969; I: 645–7

    Google Scholar 

  97. Slade CL, Andes WA, Mason AD. Platelet aggregation following defibrination with ancrod. Thromb Haemost 1976; 36: 424–9

    PubMed  CAS  Google Scholar 

  98. Lopaciuk S, Sulck K, Latallo ZS. Platelet fibrinogen during defibrase therapy [abstract]. Symposium Thrombin-like Enzymes, Trier, 1975

  99. Martin DL, Hollinger RE, Suwanwela N, et al. Experimental defibrination produced by Abbott-38414 (ancrod) and associated effects on some other factors of the hemostatic system [abstract]. Fed Proc 1971; 30: 424

    Google Scholar 

  100. Brown CH, Bell WR, Shreiner DP, et al. Effects of Arvin on blood platelets, in vitro and in vivo studies. J Lab Clin Med 1972; 79: 758–69

    PubMed  CAS  Google Scholar 

  101. Cohen D. Quantitative estimation of thrombin-antithrombin 111 and plasmin-o-antiplasmin complexes in human plasma [abstract]. V Congr Int Soc Thromb Haemostasis, Paris 1975

  102. Turpie AC, McNicol GP, Douglas AS. Platelet electrophoresis: effect of defibrination by ancrod (Arvin). Cardiovasc Res 1972; 6: 101–8

    PubMed  CAS  Google Scholar 

  103. Stocker K, Barlow GN. Characterization of defibrase. In: Martin M, Schoop W, editors. Aktuelle probleme in der Angiologie: Defibrinierung mit thrombinahnlichen Schlangengiftenzymen. Vol. 26. Stuttgart: Hans Huber Verlag, 1975: 45

    Google Scholar 

  104. Pitney WR. Clinical experience with Arvin. Thromb Diath Haemorrh 1969; 38 Suppl.: 81

    Google Scholar 

  105. Pitney WR, Holt PJ, Bray C, et al. Acquired resistance to treatment with Arvin. Lancet 1969; I(585): 79–81

    Google Scholar 

  106. Gilles HM, Reid HA, Odutola A, et al. Arvin treatment for sickle-cell crisis. Lancet 1968; II(567): 542–3

    Google Scholar 

  107. Wyss W. Wandheilung bei experimenteller Defibrinogenierung [thesis]. Zurich: University of Zurich, 1975

    Google Scholar 

  108. Ashby EC, James DC, Ellis H. The effect of intraperitoneal Malayan pit-viper venom on adhesion formation and peritoneal healing. Br J Surg 1970; 57: 863

    PubMed  CAS  Google Scholar 

  109. Donati MB, Poggi A, Mussoni L, et al. The role of fibrin formation in experimental tumor growth and metastases: a pharmacological approach with a defibrinogenating enzyme, defibrase [abstract]. Symposium Thrombin-like Enzymes, Trier, 1975

  110. Damus PS, Markland FS, Davidson TM, et al. A purified procoagulant enzyme from the venom of the Eastern Diamond Back rattlesnake (Crotalus adamanteus): in vivo and in vitro studies. J Lab Clin Med 1972; 79: 906–23

    PubMed  CAS  Google Scholar 

  111. Egberg N, Nordstrom S: In vivo effect of reptilase on fibrinogen metabolism in dogs. Scand J Clin Lab Invest 1969; 24: 383–1

    Google Scholar 

  112. Egberg N, Ljungquist A. On fibrin distribution in organs of dogs during defibrination with the thrombin-like enzymes from Bothrops atrox venom. Thromb Res 1973; 3: 191–5

    CAS  Google Scholar 

  113. Egberg N. On the metabolism of the thrombin-like enzyme from the venom of Bothrops atrox. Thromb Res 1974; 4: 35–53

    PubMed  CAS  Google Scholar 

  114. Straub PW, Bollinger A, Blaettler W. Metabolism of labelled thrombin-like snake venom enzymes. In: Martin M, Schoop W, editors. Aktuelle Probleme in der Angiologie: Defibrinierung mit thrombinahnlichen Schlangengiftenzymen. Vol. 26. Stuttgart: Hans Huber Verlag, 1975: 72

    Google Scholar 

  115. Pitney WR, Regoeczi E. Inactivation of Arvin by plasma proteins. Br J Haematol 1970; 19: 67–81

    PubMed  CAS  Google Scholar 

  116. Matsuda T, Hideno K, Ogawara M, et al. Therapeutic defibrination by Bothrops marajoensis venom. Nippon Ketsueki Gakkai Zasshi 1975; 38: 299–305

    PubMed  CAS  Google Scholar 

  117. Ashford A, Bunn DRG. The effect of Arvin on reticuloendothelial activity in rabbits. Br J Pharmacol 1970; 40: 37–44

    PubMed  CAS  Google Scholar 

  118. Klein MD, Bell WR, Nasser N, et al. The effect of Arvin upon cardiac function. Proc Soc Exp Biol Med 1969; 132: 1123–6

    PubMed  CAS  Google Scholar 

  119. Marshall R, Esnouf MP. The effect of crude and purified Ancistrodon rhodostoma venom in the dog. Clin Sci 1968; 35: 251–9

    PubMed  CAS  Google Scholar 

  120. Fedor EJ, Brondyk HB, Wiemeler LH, et al. Effect of Abbott-38414 (ancrod) on renal blood flow and clearance, coronary sinus flow, pO2 and femoral arterial blood flow. Fed Proc 1971; 30: 422

    Google Scholar 

  121. Holt PJL, Holloway V, Raghupati N, et al. Effect of a fibrinolytic agent (Arvin) on wound healing and collagen formation. Ann Rheum Dis 1970; 29: 335–6

    PubMed  CAS  Google Scholar 

  122. Silberman S, Kwaan HC. The effect of Arvin on wound healing in the rat. Fed Proc 1971; 30: 424

    Google Scholar 

  123. Browse NC. Vein surgery during defibrination. In: Martin M, Schoop W, editors. Aktuelle Probleme in der Angiologie: Defibrinierung mit thrombinahnlichen Schlangengiftenzymen. Vol. 26. Stuttgart: Hans Huber Verlag, 1975: 152

    Google Scholar 

  124. Ford PM, Bell WR, Bluestone R, et al. The effect of Arvin on experimental immune arthritis in rabbits. Br J Exp Pathol 1970; 51: 81–6

    PubMed  CAS  Google Scholar 

  125. Bluemel J, Krief G, Kutschera H. Eingluss der therapeutischen. Defibrinierung und Faktor X substitution auf die Wendress-festikeit in Tierversuch Langenbacks. Arch Chir Forum 1 1974; Suppl. 1: 245

    Google Scholar 

  126. Barlow GH, Martin DL, Tekeli S, et al. Effect of treatment with ancrod (Venacil) on healing of myocardial infarction in the pigtail monkey [abstract]. Symposium Thrombin-like Enzymes, Trier, 1971

  127. Ross JW, Bunn DGR, Ashford A. Antigenicity of Arvin. Lancet 1969; 1: 310

    PubMed  CAS  Google Scholar 

  128. Vinazzer H. Acquired resistance to ancrod. Its evaluation and clinical occurrence. Thromb Diath Haemorrh 1973; 29: 339–46

    PubMed  CAS  Google Scholar 

  129. Sapru RP, Moza AK, Kuman M, et al. Antibodies to Arvin following prolonged intravenous therapy. Thromb Res 1975; 7: 635–41

    PubMed  CAS  Google Scholar 

  130. Latallo ZB, Lopaciuk S. New approach to thrombolytic therapy. The use of defibrase in connection with streptokinase. Thromb Diath Haemorrh 1973; 56 Suppl.: 253

    CAS  Google Scholar 

  131. Martin DL, Amel H. The technique and laboratory control of subcutaneously administered defibrase [abstract]. Symposium Thrombin-like Enzymes, Trier, 1975

  132. Stocker K, Yeh H. A simple and sensitive test for the detection of inhibitors of defibrase and Arvin in serum. Thromb Res 1975; 6: 189–94

    PubMed  CAS  Google Scholar 

  133. Atkinson RP. Ancrod in the treatment of acute ischaemic stroke. Drugs 1997; 54 Suppl. 3: 100–8

    Google Scholar 

  134. Davies JA, Merrick MV, Sharp AA, et al. Controlled trial of ancrod and heparin in treatment of deep-vein thrombosis of lower limb. Lancet 1972; 1: 113–5

    PubMed  CAS  Google Scholar 

  135. Tibbett DA, Williams EW, Walker MW, et al. Controlled trial of ancrod and streptokinase in the treatment of deep vein thrombosis of lower limb. Br J Haematol 1974; 27: 407–14

    Google Scholar 

  136. Forbes CD, Prentice CRM, Barbenell J, et al. Sequence therapy with ancrod followed by streptokinase for thrombotic disorders. Br J Haematol 1973; 24: 663

    Google Scholar 

  137. Bourgain RH, Six F. The effect of defibrase on arterial thrombus formation. Thromb Res 1975; 6: 195–200

    PubMed  CAS  Google Scholar 

  138. Ehringer H, Dudczak R, Lechner K. A new approach in the treatment of peripheral arterial occlusion: defibrination with Arvin. Angiology 1974; 25: 279–89

    PubMed  CAS  Google Scholar 

  139. Blomback M, Egberg N, Gruder E, et al. Treatment of thrombotic disorders with reptilase. Thromb Diath Haemorrh 1971; 45 Suppl.: 51

    Google Scholar 

  140. Bell WR. Management of priapism by therapeutic defibrination. N Engl J Med 1969; 280: 649–50

    PubMed  CAS  Google Scholar 

  141. Latallo ZS. Report of the task force on clinical use of snake venom enzymes. Thromb Haemost 1978; 39: 768–74

    PubMed  CAS  Google Scholar 

  142. Kakkar W, Flanc C, Howe CT, et al. Treatment of deep venous thrombosis: a trial of heparin, streptokinase and Arvin. BMJ 1969; 1: 806–10

    PubMed  CAS  Google Scholar 

  143. Pitney WR. An appraisal of therapeutic defibrination. Thromb Diath Haemorrh 1971; 45 Suppl.: 43–9

    Google Scholar 

  144. Silberman S, Bernik MB, Potter EV, et al. Effects of ancrod (Arvin) in mice. Br J Haematol 1973; 24: 101–13

    PubMed  CAS  Google Scholar 

  145. Latallo ZS, Lopaciuk S. A combined treatment with streptokinase and defibrase. A new approach to therapy of thromboembolic states [abstract]. Third Congress of International Society on Thrombosis and Haemostasis, Washington, DC, 1972: 432

  146. Lopaciuk S, Meessner J, Ziemski JM, et al. Defibrination as follow-up of thrombolytic therapy. In: Martin M, Schoop W, editors. Aktuelle Probleme in der Angiologie: Defibrinierung mit thrombinahnlichen Schlangengiftenzymen. Vol. 26. Stuttgart: Hans Huber Verlag, 1975: 191

    Google Scholar 

  147. Volker D, Martin M. Verhalten der Blulviskositat unter Defibrase und Kombinitierten Therapie mit Defibrase und Streptokinase. Verh Dtsch Ges Inn Med 1973; 79: 1338–40

    PubMed  CAS  Google Scholar 

  148. Tesar J, George S. Inhibitor of activation of alternate pathway of complement by Arvin. Clin Res 1973; 21: 840

    Google Scholar 

  149. Olsson P. Discussion. In: Martin M, Schoop W, editors. Aktuelle Probleme in der Angiologie: Defibrinierung mit thrombinahnlichen Schlangengiftenzymen. Vol. 26. Stuttgart: Hans Huber Verlag, 1975: 179

    Google Scholar 

  150. Ehringer HR. Side effects. In: Martin M, Schoop W, editors. Aktuelle Probleme in der Angiologie: Defibrinierung mit thrombinahnlichen Schlangengiftenzymen. Vol. 26. Stuttgart, Hans Huber Verlag, 1975: 242

    Google Scholar 

  151. Sharp AA. Clinical use of Arvin. Thromb Diath Haemorrh 1971; 45 Suppl.: 69–71

    Google Scholar 

  152. Larsson KS. Action of salicylates on prenatal development. In: Tuchmann-Duplesis II, editor. Congenital malformation of mammalia. Paris: Masson & Cie, 1970: 171

  153. Johnsson H, Niklasson PM. The effect of moderate doses of chlorpromazine on haemostasis in dogs defibrinogenated with defibrase. Thromb Res 1974; 4: 229–36

    PubMed  CAS  Google Scholar 

  154. Penn GB, Ross JW, Ashford A. The effects of Arvin on pregnancy in the mouse and the rabbit. Toxicol Appl Pharmacol 1971; 20: 460–73

    PubMed  CAS  Google Scholar 

  155. Kwaan HC, Lo R, McFadzean AJS. Antifibrinolytic activity in primary carcinoma of the liver. Clin Sci 1959; 18: 251

    PubMed  CAS  Google Scholar 

  156. Mohler ER, Kennedy JN, Brakman P. Blood coagulation and fibrinolysis in multiple myeloma. Am J Med Sci 1967; 253: 325–32

    PubMed  Google Scholar 

  157. Sharp AA, Howie B, Biggs R, et al. Defibrination syndrome in pregnancy: value of various diagnostic tests. Lancet 1958; 2: 1309–12

    PubMed  CAS  Google Scholar 

  158. Clauss A. Gerinnungsphysiologische Schnellmethode zur bestimmung des fibrinogens. Acta Haematol 1957; 17: 237–46

    PubMed  CAS  Google Scholar 

  159. Ratnoff OD, Menzie C. A new method for the determination of fibrinogen in small samples of plasma. J Lab Clin Med 1951; 37: 316–20

    PubMed  CAS  Google Scholar 

  160. Engleken HJ. Gerinnungsphysiologische Untersuchungen und klinische beobachtungen bei der behandlung mit dem thrombinahulichen Schlangengiftenzyme defibrase dissertation [dissertation]. Department of Physiology, University of Bonn, Bonn, West Germany: 1974

    Google Scholar 

  161. Funk C, Gunur J, Herold R, et al. Reptilase-R: a new reagent in blood coagulation. Br J Haematol 1971; 21: 43–52

    PubMed  CAS  Google Scholar 

  162. Kubisz P. Cold-induced retraction of reptilase clots. Scand J Haematol 1974; 13: 175–8

    PubMed  CAS  Google Scholar 

  163. Kubisz P, Suranova J. Reptilase clot retraction test. Pathol Biol 1975; 23: 269–75

    PubMed  CAS  Google Scholar 

  164. Palester-Chlebowczyk M, Strzyzewska E, Latallo ZS. Preliminary results of the reptilase clotting time and protamine test in patients undergoing open heart surgery with extracorporeal circulation. J Clin Pathol 1972; 25: 625

    PubMed  CAS  Google Scholar 

  165. Allison JV. Comparison of thrombin and ancrod as clotting reagents to test for deficiency of plasma fibrinogen. Proc Univ Otago Med Sch 1972; 50: 41–2

    Google Scholar 

  166. Bell WR, Tomasulo PA, Alving BM, et al. Thrombocytopenia occurring during the administration of heparin. A prospective study in 52 patients. Ann Intern Med 1976; 85: 155–60

    PubMed  CAS  Google Scholar 

  167. Bell WR, Anderson ND, Anderson AO. Heparin-induced coagulopathy. J Lab Clin Med 1977; 89: 741–50

    PubMed  CAS  Google Scholar 

  168. Green D. A simple method for the purification of factor VIII (AHG) employing snake venom. J Lab Clin Med 1971; 77: 153–8

    PubMed  CAS  Google Scholar 

  169. Lopaciuk S, Latallo Z. Separation of human antihaemophilic factor (AllF, factor VIII) from fibrinogen by means of defibrase (Reptilase) [abstract]. IV Int Cong Thromb Haemostasis, Vienna, 1973

  170. Kirby EP, Niewiarowski S, Stocker K, et al. Thrombocytin: a serine protease from Bothrops atrox venom. I. Purification and characterization of the enzyme. Biochemistry 1979; 18: 3564–70

    PubMed  CAS  Google Scholar 

  171. Niewiarowski S, Kirby EP, Brudzynski TM, et al. Thrombocytin: a serine protease from Bothrops atrox venom. II. Interaction with platelets and plasma-clotting factors. Biochemistry 1979; 18: 3570–77

    PubMed  CAS  Google Scholar 

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  1. Division of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland, 21287-4928, USA

    William R. Bell Jr MD PhD

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Bell, W.R. Defibrinogenating Enzymes. Drugs 54 (Suppl 3), 18–31 (1997). https://doi.org/10.2165/00003495-199700543-00005

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