Coagulation studies on „Reptilase”, an extract of the venom from Bothrops jararaca

Summary

Reptilase — the clot-promoting extract of the venom of Bothrops jararaca — was found to have a thrombin-like activity. No effect could be demonstrated in the first phase of coagulation. Unlike bovine thrombin it was not inactivated by heparin + heparin-cofactor or by the antithrombin of normal plasma. Analyses of N-terminal aminoacids in the fibrin formed by Reptilase revealed the same aminoacids as in the fibrin formed by bovine thrombin. Quantitative differences found may reflect different specificity of the two enzymes.

It is concluded that the use of Reptilase as a haemostaticum is unwarranted.

We wish to thank Professor Erik Jorpes for valuable advice and support in this investigation.

 

• References

• 1 Astrup T, and Müllertz S. The fibrin plate method for estimating fibrinolytic activity. Arch. Biochem. Biophys. 40: 346 1952;
• 2 Bailey K, Bettelheim F. R, Lorand L, and Middlebrook W. R. Action of thrombin in the clotting of fibrinogen. Nature (Lond.) 167: 233 1951;
• 3 Bergmann M, Fruton J. S, and Pollok H. The specificity of trypsin. J. biol. Chem. 127: 643 1939;
• 4 Bellelheim F. R, and Bailey K. The products of the action of thrombin on fibrinogen. Biochim. biophys. Acta 9: 578 1952;
• 5 Biggs R, and Macfarlane R. G. Human blood coagulation and its disorders. Black-well Scientific Pubi.; Oxford: 1953
• 6 Blomback B, and Blombäck M. Purification of human and bovine fibrinogen. Arkiv for Kemi 10: 415 1956;
• 7 Blombäck B, and Yamashina I. The determination of N-terminal amino acids during the conversion of fibrinogen to fibrin. Acta Chem. Scand., 1957, in print
• 8 Breda R, Bernardi R, and Sala F. Ricerche clinico-sperimentale sull’azione coagulante del veleno di Bothrops jararaca. Giorn. Clin. med. 32: 882 1951;
• 9 Bruck H, and Salem G. Reptilase, a haemostatic for prophylactic and therapeutic use in connection with surgical operations. Wien. klin. Wschr. 66: 395 1954;
• 10 Deutsch E. Blutgerinnungsfaktoren. Franz Deuticke; Wien: 208 1955
• 11 Eagle F.L. The coagulation of blood by snake venoms and its physiological significance. J. exp. Med. 65: 613 1937;
• 12 Edman P. Preparation of phenyl thiohydantoins from some natural amino acids. Acta chem. scand. 4: 277 1950;
• 13 Edman P. Preparation of phenyl thiohydantoins from some natural amino acids. Acta scand. 4: 283 1950;
• 14 Edman P, and Sjöquist J. Identification and semiquantitative determination of phenyl thiohydantoins. Acta chem. scand. 10: 1507 1956;
• 15 Fleischhacker H. Concerning the therapy of coagulation disturbances. Wien. med. Wschr. 104: 171 1954;
• 16 Glaninger J. About the application of the hemostatic Reptilase in oto-rhino-laryngology. Mschr. Ohrenheilk. 89: 63 1955;
• 17 Heiss H. A contribution to the hemostatic therapy in cervical carcinoma. Wien. med. Wschr. 104: 833 1954;
• 18 Klobusitzky D. Biochemische Studien über die Gifte der Schlangengattung Bothrops. Arch. exp. Path. Pharmak. 179: 204 1935;
• 19 Klobusitzky D, und König P. Biochemische Studien über die Gifte der Schlangengattung Bothrops. Arch. exp. Path. Pharmak. 181: 387 1936;
• 20 Klobusitzky D, und König P. Biochemische Studien über die Gifte der Schlangengattung Bothrops. Arch. exp. Path. Pharmak. 182: 577 1936;
• 21 Lassen M. Heat denaturation of plasminogen in the fibrin plate method. Acta physiol. scand. 27: 371 1952;
• 22 Lorand L, and Middlebrook W. R. Studies on fibrino-peptide. Biochim. Biophys. Acta 9: 581 1952;
• 23 Lorand L, and Middlebrook W. R. Species specificity of fibrinogen as revealed by end-group studies. Science 118: 515 1953;
• 24 Nilsson I. M, and Wenckert A. Demonstration of a heparin-like anticoagulant in normal blood. Acta med. scand.. 150 1954 Suppl
• 25 Owren P. A. The coagulation of blood. Investigations on a new clotting factor. Acta med. scand.. 194 1947 Suppl
• 26 Owren P. A, and Aas K. The control of dicumarol therapy and the quantitative determination of prothrombin and proconvertin. Scand. J. clin. Lab. Invest. 3: 201 1951;
• 27 Porges N. Snake venoms, their biochemistry and mode of action. Science 117: 47 1953;
• 28 Ratnoff O. D. Thrombin accelerator: a clotting factor of plasma deficient in cirrhosis of the liver, multiple myeloma, and eclampsia. J. Lab. clin. Med. 42: 933 1953;
• 29 Ratnoff O. D, and Potts A. M. The accelerating effect of calcium and other cations on the conversion of fibrinogen to fibrin. J. clin. Invest. 33: 206 1954;
• 30 Rochae Silva M, and Andrade S. O. Estudos sobre a dicoumarina 3,3-metilenobis-(4-hidroxicoumarina). IL Efeito coagulante de venenos dos géneros Bothrops e Crotalus sobre o plasma oxalatado de animais normales e tratados pela dicoumarina. Arch. Inst. Biol. 16: 115 1945;
• 31 Rosenfeld G, and Jánszky B. The acclerating effect of calcium on the fibrinogen-fibrin transformation. Science 116: 36 1952;
• 32 Sanger F. The free amino groups of insulin. Biochem. J. 39: 507 1945;
• 33 Seegers W. H, Johnson J. F, and Fell C. An antithrombin reaction related to prothrombin activation. Amer. J. Physiol. 176: 97 1954;
• 34 Sherry S, and Troll W. The action of thrombin on synthetic substrates. J. biol. Chem. 208: 95 1954;
• 35 Troll W, Sherry S, and Wachman J. The action of plasmin on synthetic substrates. J. biol. Chem. 208: 85 1954;
• 36 Werbin H, and Palm A. Trypsin hydrolysis of lysine ethyl ester. J. Amer. Chem. Soc. 73: 1382 1951;