Thrombosis represents an important cause of mortality in patients with sickle cell disease, in addition to the complications caused by the primary defect of inherited abnormal hemoglobin. To study the involvement of platelets in these complications, we assessed the biosynthesis of thromboxane A 2 in samples from 49 patients with sickle cell disease and in 33 control subjects. The urinary excretion of the major arachidonic acid metabolite of platelet origin (11-dehydrothromboxane B 2 ) and of the vascular endothelial cell (2,3-dinor-6-ketoprostaglandin F lo ) were very significantly increased (p<0.0002) in the patients. In a small group of patients 0=14), we further investigated the ex vivo response of their platelets to U46619, a stable analogue of thromboxane A 2 . We observed decreased aggregation and [ 14