REDUCTION OF R-HIRUDIN INDUCED BLEEDING IN PIGS BY THE ADMINISTRATIONOF VON-WILLEBRAND-FACTOR

To prevent r-hirudin induced excess bleeding an animal model was estab lished in pigs for the investigation of an anti-bleeding strategy, We used the Simplate(R) device to monitor skin bleeding time (SET) at the inner site of the ear, r-Hirudin infused in a dose of 0.3 mg/kg per h induced a prominent increase of SET. The aim of our studies was to re verse r-hirudin induced bleeding by enhancing platelet adhesion to the endothelium via the administration of von Willebrand Factor (vWF), Pi gs were treated with vWF containing solutions (Haemate(R) and a vWF-co ncentrate) at 3 h after the start of the r-hirudin infusion, Both comp ounds suppressed SET Ih after administration and significantly prevent ed bleeding until the termination of the experiment, SET values (given in times of baseline) in the placebo group were 3.32 +/- 0.9, 1.51 +/ - 0.14 in the Haemate(R) and 1.85 +/- 0.42 in the vWF concentrate grou p (P = 0.008 or 0.032, in a two-sided Kruskall-Wallis-test). Coagulati on 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 alter ing the anticoagulant effect of r-hirudin, Addition of 20 mg/kg per h aspirin resulted in a further increase of SET. Aspirin, moreover, supp ressed platelet aggregation but did not alter platelet counts, In a fu rther study, bleeding induced by r-hirudin and aspirin was antagonized by Haemate(R) (66 U/kg i.v. bolus + 187 U/kg per h for 2 h infusion) and a significant reduction of bleeding time occurred.