Summary
We have used a whole blood single-platelet counting assay (WBSPC) that is sensitive
to microaggregation for monitoring GPIIb/IIIa antagonists and have compared this with
other methodologies. In vitro effects of the GPIIb/IIIa antagonist fradafiban on ADP-induced platelet aggregation
were determined using WBSPC and PRP turbidimetry, comparing citrate and hirudin anticoagulation.
Fradafiban was a more potent inhibitor of aggregation assessed by PRP turbidimetry
compared to WBSPC. Citrate showed only a trend towards enhancing fradafiban potency
(p = 0.087). Citrated blood from 8 patients with unstable angina, randomised to receive
oral lefradafiban (the oral prodrug of fradafiban) or placebo, was studied before
and during treatment using WBSPC, PRP turbidimetry, impedance aggregometry and Rapid
Platelet Function Assay (RPFA, Accumetrics). RPFA, PRP turbidimetry and WBSPC measurements
correlated well. Impedance aggregometry responses were oversensitive to GPIIb/IIIa
blockade. WBSPC was most discriminating at high levels of inhibition and offered a
rapid means of monitoring GPIIb/IIIa antagonist effect within the therapeutic range
of inhibition.
Key Words
Platelet aggregation - platelet aggregation inhibitors - unstable angina