The influence of infusions of 1-desamino-8-D-arginine vasopressin (DDAVP) in vivo on the anticoagulant effect of recombinant hirudin (CGP39393) in vitro.
Hirudin is a specific, potent inhibitor of thrombin that may be a valuable antithrombotic agent. The aim of this study was to investigate the hypothesis that the haemostatic effects of DDAVP counteract the coagulation defect induced by hirudin. The effect of DDAVP was studied in vivo on the anticoagulant action of recombinant hirudin (CGP39393) in vitro. Blood samples were taken at intervals from 10 normal volunteers infused with DDAVP. Factor VIII:C rose from (mean) 0.68 IU/ml before DDAVP to 2.19 and 2.16 IU/ml after 30 and 60 min infusion, respectively. Samples taken during DDAVP infusion showed a dose related decrease in the hirudin (0.5 and 1.0 microM) induced prolongation of the APTT, that occurred at FVIII:C concentrations of up to twice normal. At higher concentrations of hirudin no effect on the APTT occurred. These results demonstrate that DDAVP infusion elevates factor VIII:C levels with an associated significant reduction in the anticoagulant effect of hirudin in vitro.
Ibbotson
S H
SH
University Department of Medicine, General Infirmary, Leeds, UK.
Grant
P J
PJ
Kerry
R
R
Findlay
V S
VS
Prentice
C R
CR
D000925:Anticoagulants / Q000037:antagonists & inhibitors*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D005169:Factor VIII / Q000187:drug effects; D006629:Hirudins / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin; C060225:desirudin