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Abstract
BackgroundPlatelet activation has been implicated in the pathogenesis of sickle cell disease (SCD) suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study.MethodsThe primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41) or placebo (n = 21) for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients.ResultsThere were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain) and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events.ConclusionsDespite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain.
Highlights
Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD) suggesting antiplatelet agents may be therapeutic
Sickle cell disease (SCD) results from a mutation in the β-globin gene
The clinical manifestations of disease are due to hemolysis, and intermittent microvascular occlusion marked by painful vaso-occlusive crisis (VOC) and eventual end-organ damage from repeated bouts of ischemiareperfusion injury resulting in significant disabilities and early mortality
Summary
Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD) suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study. Sickle cell disease (SCD) (the common term used for the clinical syndrome that results from homozygous hemoglobin S; compound heterozygous Hb S/C; and compound heterozygous Hb S/β0/+-thalassemia) results from a mutation in the β-globin gene. Previous work, using various soluble and immunological biomarkers, has shown that platelets are activated in patients with SCD [10,11,12]. Some data have suggested increased platelet activation during VOC [12,13,14]. Possible mechanisms whereby activated platelets contribute to the pathogenesis of VOC include release of thrombospondin 1
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