Hirudin causes more bleeding than heparin in a rabbit ear bleeding model.
This study was undertaken to determine the appropriateness of the current practice of using the activated partial thromboplastin time (APTT) to select hirudin doses. A rabbit bleeding ear model was used to compare the effects of various doses of heparin and hirudin on the relationship between the APTT and bleeding. In addition, the effects of these agents on the thrombin clotting time (TCT) and factor Xa clotting time also were examined. Both heparin and hirudin produced a concentration-dependent increase in bleeding. When bleeding was plotted as a function of APTT ratio, even a small increase in APTT ratio within the therapeutic range of 1.5 to 2.5 resulted in a marked increase in bleeding with hirudin but not with heparin. The TCT was more responsive than the APTT or factor Xa clotting time to increases in hirudin-induced bleeding. In this model, hirudin produces more bleeding than heparin when the agents are used in doses that increase the APTT ratio to the same extent. These studies highlight the pitfalls of extrapolating from experience with heparin when choosing a test to monitor new antithrombotics. Our findings also suggest that the TCT may be more responsive than the APTT for monitoring hirudin therapy.
Klement
P
P
McMaster University and Hamilton Civic Hospitals Research Centre, Ontario, Canada.
Liao
P
P
Hirsh
J
J
Johnston
M
M
Weitz
J I
JI
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D000990:Antithrombin III / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D004431:Ear, External / Q000098:blood supply / Q000187:drug effects; D015951:Factor Xa / Q000032:analysis / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage*; D006629:Hirudins / Q000008:administration & dosage*; D007275:Injections, Intravenous; D010314:Partial Thromboplastin Time; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage; D013047:Specific Pathogen-Free Organisms
D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; D000990:Antithrombin III; D006493:Heparin; D015951:Factor Xa