Summary
The APTT has been considered the most suitable candidate to monitor the anticoagulant
activity of hirudin. However, its use is hampered by problems of standardization,
which make the results heavily dependent on the responsiveness of the reagent used.
Our aim was to investigate if this different responsiveness of different reagents
when added in vitro is to be confirmed in an ex vivo study.
Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered
subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation
of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All
groups exhibited a significant prolongation of APTT 2 h after sc administration of
hirudin, both at low and high doses. But 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 the same APTT reagents in an in vitro study in which
normal pooled plasma 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 with the silica-based reagents, but
this effect is exclusive for the ex vivo model.
