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

Citation
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
Citations number
21
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
CORONARY ARTERY DISEASE
ISSN journal
09546928 → ACNP
Volume
12
Issue
3
Year of publication
2001
Pages
245 - 253
Database
ISI
SICI code
0954-6928(200105)12:3<245:QBFCOT>2.0.ZU;2-8
Abstract
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.