EFFECTS OF 2 DIFFERENT DOSES OF HIRUDIN ON APTT, DETERMINED WITH 8 DIFFERENT REAGENTS

The APTT has been considered the most suitable candidate to monitor th e anticoagulant activity of hirudin. However, its use is hampered by p roblems of standardization, which make the results heavily dependent o n the responsiveness of the reagent used. Our aim was to investigate i f this different responsiveness of different reagents when added in vi tro is to be confirmed in an ex vivo study. Two different doses of r-h irudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutane ously to 20 New Zealand male rabbits, and the differences in prolongat ion of APTT 2 and 12 h later were compared, using 8 widely used commer cial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. B ut this prolongation persisted 12 h later only when the PTTa reagent ( Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica-based reagents. In a further study, we compared t he same APTT reagents in an in vitro study in which normal pooled plas ma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most wit h the silica-based reagents, but this effect is exclusive for the ex v ivo model.