Increased ability of tirofiban to maintain its inhibitory effects on the binding of fibrinogen to platelets in blood from patients with and without diabetes mellitus

OBJECTIVESBoth tirofiban and eptifibatide release rapidly from glycoprotein IIb–IIIa but have different dissociation constants (KD of tirofiban=15 nmol/l, of eptifibatide=120 nmol/l). Binding of fibrinogen to glycoprotein IIb–IIIa is biphasic, forming an initial reversible complex (KD=155–180 nmol/l) and a second more stable complex (KD=20–70 nmol/l). Diabetes is known to alter platelet function. To determine the influence of affinity on inhibitory effects in blood from patients with (n=20) and without (n=20) diabetes mellitus, we characterized the extent of inhibition as a function of time. METHODSBlood was added to reaction tubes containing tirofiban 100 ng/ml or eptifibatide 1.7 μg/ml (concentrations previously defined to be optimal) plus a platelet agonist (1 μmol/l adenosine diphosphate or 25 μmol/l thrombin receptor agonist peptide), and fluorochrome-labeled fibrinogen before analysis by flow cytometry. RESULTSThe extent of inhibition early on (30 s to 3 min) was similar (>85%) with either agent in blood from those with and without diabetes mellitus, whereas the extent of inhibition 10–15 min later was maintained more effectively with tirofiban than with eptifibatide (difference in slope P