Reduction of r-hirudin induced bleeding in pigs by the administration of von Willebrand factor
作者:
DickneiteG.,
J.H.,
KumpeG.,
ReersM.,
期刊:
Platelets
(Taylor Available online 1996)
卷期:
Volume 7,
issue 5-6
页码: 283-290
ISSN:0953-7104
年代: 1996
DOI:10.3109/09537109609023590
出版商: Taylor&Francis
数据来源: Taylor
摘要:
To prevent r-hirudin induced excess bleeding an animal model was established in pigs for the investigation of an anti-bleeding strategy. We used the Simplate®device to monitor skin bleeding time (SBT) at the inner site of the ear. r-Hirudin infused in a dose of 0.3 mag per h induced a prominent increase of SBT. The aim of our studies was to reverse r-hirudin induced bleeding by enhancing platelet adhesion to the endothelium via the administration of von Willebrand Factor (vWF). Pigs were treated with vWF containing solutions (Haemate®and a vWF-concentrate) at 3h after the start of the r-hirudin infusion. Both compounds suppressed SBT 1h after administration and significantly prevented bleeding until the termination of the experiment. SBT values (given in times of baseline) in the placebo group were 3.32±0.9, 1.51±0.14 in the Haemate®and 1.85±0.42 in the vWF concentrate group (P= 0.008 or 0.032, in a two-sided Kruskall-Wallis-test). Coagulation parameters (aPTT, PT) were unaltered by the treatment, as were the r-hirudin plasma levels suggesting that vWF is not an antidote in its strict sense. It is concluded that vWF reverses bleeding without altering the anticoagulant effect of r-hirudin. Addition of 20 mg/kg per h aspirin resulted in a further increase of SBT. Aspirin, moreover, suppressed platelet aggregation but did not alter platelet counts. In a further study, bleeding induced by r-hirudin and aspirin was antagonized by Haemate®(66 Ukg i.v. bolus + 187 Ukg per h for 2 h infusion) and a significant reduction of bleeding time occurred.
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