ELEVATED URINARY LEVELS OF THROMBOXANE AND PROSTACYCLIN METABOLITES IN SICKLE-CELL DISEASE REFLECTS ACTIVATED PLATELETS IN THE CIRCULATION

There is evidence for increased factor VII turnover and the associated increased thrombin generation and fibrinolytic activities in sickle c ell disease (SCD) that may affect in vivo platelet and endothelial cel l reactivity. We studied the release of specific eicosanoids that are indicative of in vivo platelet activation and endothelial cell injury. The circulating and urinary levels of 2,3-dinor thromboxane B-2(2,3-d inor-TxB(2)), TxB(2), PGI(2) [as 6-keto-PGF(1 alpha)] and PGE(2) were measured in 15 HbSS patients, eight HbAA nonhaemolytic anaemic individ uals and 12 healthy HbAA controls using specific RIAs. The mean urinar y 2,3-dinor-TxB(2) in the HbSS patients was significantly higher than in both the healthy HbAA and the anaemic controls. 6-keto-PGF(1 alpha) was undetected in the urines of the healthy HbAA controls, but was me asured insignificant amounts in the HbSS and the HbAA anaemic patients . The urinary concentrations of PGE(2) and TxB(2) in HbSS patients' sa mples were also significantly higher than those of both control groups (P < 0.05). PGE(2) and TxB(2) levels were below the detection limit i n the plasmas of the HbAA subjects, but were measurable in the HbSS an d HbAA anaemic plasmas. The plasma level of 6-keto-PGF(1 alpha) in the HbSS patients was also significantly higher than in the control group s. The data indicates a persistent inflammatory process in the HbSS pa tients, and is consistent with the hypothesis that there is platelet a nd endothelial cell activation in SCD.