837 INCREASED PLASMA THROMBOXANE LEVELS IN SICKLE CELL DISEASE

Abstract

Platelet function abnormalities, i.e., increased circulating platelet aggregates and decreased platelet aggregation, have been observed in sickle cell disease patients. To determine the mechanism of these abnormalities, we studied 13 patients with sickle cell disease and 10 normal subjects. Peripheral venous blood samples were collected for plasma thromboxane B2 (TXB2) (stable metabolite of TXA2) determinations by radioimmunoassay. In addition, platelets were stimulated with sodium arachidonate (1 mM) and thrombin (10 units/m1), and platelet TXB2 generation quantitated. In 11 patients in steady state, plasma TXB2 levels were increased compared to normal subjects (480 ± 41 vs 252 ± 37 pg/ml, P<0.01). In contrast, platelet TXB2 generation in response to sodium arachidonate was lower in patients with sickle cell disease (44 ± 10 vs 103 ± 32 pg/108 platelets, P<0.01). Similarly, thrombin-induced platelet TXB2 generation was decreased (186 ± 45 vs 801 ± 320 pg/108 platelets, P<0.01). In 2 patients with acute vaso-occlusion, plasma TXB2 levels were extremely high (1650 and 1350 pg/m1), but platelet TXB2 generation was similar to those in steady state. Increased plasma TXB2 levels in sickle cell disease patients imply continuous platelet activation and may be a mechanism of increase in circulating platelet aggregates. Decrease in platelet TXB2 generation suggests either substrate or enzyme deficiency due to persistent platelet activation, and may be the cause of decreased platelet aggregation.