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.

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