APROTININ REDUCES CLOPIDOGREL-INDUCED PROLONGATION OF THE BLEEDING-TIME IN THE RAT

High doses of aprotinin have been shown to reduce blood loss and blood transfusion requirements in patients undergoing open heart surgery an d recent studies in animals have shown that aprotinin was able to redu ce bleeding associated with rt-PA administration. Our study was design ed to demonstrate an effect of aprotinin (Iniprol(R)) on the prolongat ion of the bleeding time associated with the treatment with a potent a nalogue of ticlopidine: clopidogrel. Bleeding time was determined in r ats by transection of the tip of the tail. 2 hours after a single oral administration, clopidogrel (5 mg/kg, p.o.), induced a 4-fold increas e in the bleeding time. Aprotinin administered as a bolus iv injection followed by continuous infusion strongly reduced bleeding time prolon gation associated with clopidogrel treatment. This effect was dose-rel ated and reached a maximum (congruent-to 50% inhibition - P<0.001) at and above the total dose of 40 U Ph Eur/kg (80,000 KIU/kg ). After adm inistration of a total dose of 60 U Ph Eur/kg (120,000 KIU/kg), aproti nin modified neither the antiaggregating effect of clopidogrel nor its antithrombotic activity, as determined in various experimental models . For this reason, aprotinin might constitute a useful antagonist of t he haemorrhagic risk associated with interventional therapy under trea tment with ticlopidine or clopidogrel.