Thromb Haemost 1991; 65(04): 355-359
DOI: 10.1055/s-0038-1648151
Original Article
Schattauer GmbH Stuttgart

Experimental Studies on a Recombinant Hirudin, CGP 39393

E Gray
The National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, UK
,
J Watton
The National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, UK
,
S Cesmeli
The National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, UK
,
T W Barrowcliffe
The National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, UK
,
D P Thomas
The National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, UK
› Author Affiliations
Further Information

Publication History

Received: 03 September 1990

Accepted after revision 20 November 1990

Publication Date:
02 July 2018 (online)

Summary

The in vitro anticoagulant activities of recombinant desulphatohirudin (r-hirudin) were studied in the activated partial thromboplastin time (APTT) and the thrombin generation test : systems. In the APTT at concentrations below 5 μg/ml, r-hirudin showed a dose-response curye. At concentrations above 5 μg/ml, the plasma became unclottable, but in the thrombin generation test , at least 10 μg/ml of r-hirudin was required for full inhibition of thrombin generation. The antithrombotic effect was assessed using a rabbit venous stasis model; 150 μg/ml r-hirudin completely prevented thrombus formation at 10 and 20 min stasis. At antithrombotic dose, the mean bleeding time ratio measured in a rabbit ear template model, was not prolonged over control values. At higher doses, the bleeding time ratios were higher than those observed for the same dosage of heparin. These data indicate that while r-hirudin is an effective antithrombotic agent, antithrombotic doses have to be carefully titrated to avoid excessive bleeding.