The alphaIIbbeta3 antagonist
eptifibatide is an effective treatment for patients with
acute coronary syndromes (ACS). Platelet reactivity and
CD40 ligand (
CD40L) may play a role in the pathophysiology of sickle cell anaemia (SCA) similar to that in ACS, suggesting that inhibition of platelet aggregation and
CD40L release by
eptifibatide may benefit patients with SCA. Following
eptifibatide infusion, safety and pharmacodynamic data were obtained from four SCA patients in their non-crisis, steady states.
Eptifibatide was well tolerated, with no adverse changes in the haematological, biochemical or coagulation parameters studied.
Eptifibatide did not increase plasma levels of
platelet factor 4 or
beta-thromboglobulin,
P-selectin exposure or platelet:leucocyte aggregate formation. Moreover, decreases in platelet aggregation and soluble
CD40L (sCD40L) levels achieved in SCA patients were comparable to those observed in the treatment of ACS. Finally, indicators of
inflammation, macrophage inflammatory protein-1alpha, tumour
necrosis factor-alpha and
myoglobin were reduced following
eptifibatide infusion, while vasodilation correlatives,
matrix metalloproteinases (MMP-2 and MMP-9) and
leptin were increased. Based on these phase I results,
eptifibatide may benefit SCA patients by inhibiting platelet aggregation, decreasing sCD40L levels and favourably altering plasma levels of inflammatory mediators.