Quantification by flow cytometry of the efficacy of and interindividual variation of platelet inhibition induced by treatment with tirofiban and abciximab.
BACKGROUND
After exposure of platelets to abciximab and tirofiban in vitro, we have observed variable inhibition of fibrinogen binding and a lack of inhibition of alpha-granule degranulation.


METHODS
To determine whether such changes occur with treatment, platelet reactivity was assayed in blood from 50 patients receiving abciximab or tirofiban.


METHODS
Platelet reactivity was determined before and during steady-state infusions of abciximab (0.125 microg/kg/min) or tirofiban, with either the PRISM-PLUS dosage (0.1 microg/kg/min) or the RESTORE dosage (0.15 microg/kg/min). Fibrinogen binding and P-selectin expression were determined by flow cytometry after stimulation of platelets with ADP (0.2 or 1 microM) or thrombin-receptor agonist peptide (TRAP, 25 microM).


RESULTS
Both dosages of tirofiban and abciximab reduced fibrinogen binding in response to 0.2 microM ADP comparably. However, fibrinogen binding in response to 1.0 microM ADP or 25 microM 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.


CONCLUSIONS
The RESTORE dosages of tirofiban and abciximab each inhibit fibrinogen binding and alpha-granule degranulation similarly. However, substantial interindividual variation in inhibition of fibrinogen binding is evident.
Holmes
M B
MB
Department of Medicine, The University of Vermont College of Medicine, USA. michael.holmes@vtmednet.org
Kabbani
S S
SS
Terrien
C M
CM
Watkins
M W
MW
Sobel
B E
BE
Schneider
D J
DJ
D000077284:Abciximab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy*; D005260:Female; D005340:Fibrinogen / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000077466:Tirofiban; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; D005340:Fibrinogen; D000077466:Tirofiban; D000077284:Abciximab