Antithrombotic activity of recombinant hirudin in the rat: a comparative study with heparin.
Hirudin, a potent inhibitor of blood coagulation, differs in its antithrombotic activity according to the source of isolation. It was therefore of interest to study recombinant hirudin. Hirudin was obtained by a genetic process from E. coli. Its antithrombotic action was investigated in an experimental (rat) model of venous thrombosis and was compared to heparin whose results are known. Heparin (400 micrograms/kg) and hirudin (12.5, 25 and 50 micrograms/kg) present an antithrombotic effect and limit the extension of an existing thrombus (p less than 0.05). Higher heparin dosages increase the bleeding time mean value (p less than 0.05) whereas hirudin does not. So, recombinant hirudin presents the same antithrombotic action as heparin but with very inferior dosage. This activity seems not dose-dependent and is associated to weak hemorrhagic effects.
Laboratoire d'hématologie, Faculté de Pharmacie, Bordeaux, France.
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Doutremepuich
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Deharo
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Guyot
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MC
Lalanne
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Walenga
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Fareed
D000818:Animals; D001760:Bleeding Time; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000502:physiology; D015951:Factor Xa; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage; D008026:Ligation; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D012212:Rheology; D012697:Serine Endopeptidases / Q000032:analysis; D013927:Thrombosis / Q000188:drug therapy*; D014684:Venae Cavae
D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin; D012697:Serine Endopeptidases; D015951:Factor Xa