Quantification by flow cytometry of the efficacy of and interindividual variation of platelet inhibition induced by treatment with tirofiban and abciximab

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Abstract
After exposure of platelets to abciximab and tirofiban in vitro, we have observed variable inhibition of fibrinogen binding and a lack of inhibition of α-granule degranulation. To determine whether such changes occur with treatment, platelet reactivity was assayed in blood from 50 patients receiving abciximab or tirofiban. Platelet reactivity was determined before and during steady-state infusions of abciximab (0.125 μg/kg/min) or tirofiban, with either the PRISM-PLUS dosage (0.1 μg/kg/min) or the RESTORE dosage (0.15 μg/kg/min). Fibrinogen binding and P-selectin expression were determined by flow cytometry after stimulation of platelets with ADP (0.2 or 1 μM) or thrombin-receptor agonist peptide (TRAP, 25 μM). Both dosages of tirofiban and abciximab reduced fibrinogen binding in response to 0.2 μM ADP comparably. However, fibrinogen binding in response to 1.0 μM ADP or 25 μM TRAP was inhibited to a greater extent by the RESTORE dosage of tirofiban and abciximab than by the PRISM-PLUS dosage of tirofiban (P < 0.05). Furthermore, only the RESTORE dosage of tirofiban and abciximab reduced P-selectin expression in response to ADP. Inhibition with each regimen varied markedly between patients. The RESTORE dosages of tirofiban and abciximab each inhibit fibrinogen binding and α-granule degranulation similarly. However, substantial interindividual variation in inhibition of fibrinogen binding is evident.

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