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HF Kotze, S Lamprecht and PN Badenhorst
Department of Haematology, University of The Orange Free State,
Bloemfontein, Republic of South Africa.
Intravenous recombinant (r)-hirudin has a potent antithrombotic effect in
aspirin- and heparin-resistant platelet-dependent thrombus formation in
baboon models. However, these thrombi reform when therapy is stopped after
60 minutes. To determine if 4 hours of therapy can produce a lasting
antithrombotic effect, we investigated the extent of deposition of
111In-labeled platelets onto 0.5-cm2 segments of Dacron vascular grafts for
53 hours. These grafts had been incorporated into exteriorized permanent
femoral arteriovenous shunts in baboons. Platelet deposition in eight
untreated animals was generally sigmoidal. Maximum platelet deposition,
1.7% +/- 0.9% of injected labeled platelets, was reached after
approximately 4 hours. Deposition then gradually decreased to 0.4% +/- 0.2%
of injected labeled platelets after 53 hours. After a thrombus was allowed
to form for 15 minutes in six animals, intravenous treatment with r-hirudin
at a dose of 20 nmol (0.14 mg)/kg-min-1 (aPTT > 300 seconds) was started
and maintained for 4 hours. Platelet deposition was interrupted during
treatment. After infusion was stopped, platelets accumulated again, but not
as much as in the untreated animals. Maximum platelet deposition, 0.7% +/-
0.2% of injected labeled platelets, was significantly less (P < .01),
and was reached after approximately 23 hours. Thereafter, deposition
decreased to 0.4% +/- 0.2% at 53 hours. The shunts in all of the untreated
animals occluded at some stage during the study, while only one shunt
occluded in the treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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| Copyright © 1995 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||