Quantification by flow cytometry of the efficacy of and interindividual variation of platelet inhibition induced by treatment with tirofiban and abciximab
Mb. Holmes et al., Quantification by flow cytometry of the efficacy of and interindividual variation of platelet inhibition induced by treatment with tirofiban and abciximab, CORON ART D, 12(3), 2001, pp. 245-253
Background After exposure of platelets to abciximab and tirofiban in vitro,
we have observed variable inhibition of fibrinogen binding and a lack of i
nhibition of ct-granule degranulation.
Design To determine whether such changes occur with treatment, platelet rea
ctivity was assayed in blood from 50 patients receiving abciximab or tirofi
ban.
Methods Platelet reactivity was determined before and during steady-state i
nfusions of abciximab (0.125 mug/kg/min) or tirofiban, with either the PRIS
M-PLUS dosage (0.1 mug/kg/min) or the RESTORE dosage (0.15 mug/kg/min). Fib
rinogen binding and P-selectin expression were determined by flow cytometry
after stimulation of platelets with ADP (0.2 or 1 muM) or thrombin-recepto
r agonist peptide (TRAP, 25 muM).
Results Both dosages of tirofiban and abciximab reduced fibrinogen binding
in response to 0.2 muM ADP comparably. However, fibrinogen binding in respo
nse to 1.0 muM ADP or 25 muM 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 wit
h each regimen varied markedly between patients.
Conclusions The RESTORE dosages of tirofiban and abciximab each inhibit fib
rinogen binding and cr-granule degranulation similarly. However, substantia
l interindividual variation in inhibition of fibrinogen binding is evident.
Coron Artery Dis 12:245-253 (C) 2001 Lippincott Williams & Wilkins.