title: Elevated urinary levels of thromboxane and prostacyclin metabolities in sickle cell disease reflects activated platelets in the circulation.
abstract: There is evidence for increased factor VII turnover and the associated increased thrombin generation and fibrinolytic activities in sickle cell disease (SCD) that may affect in vivo platelet and endothelial cell 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 B2(2,3-dinor-TxB2),TxB2,PGI2 [as 6-keto-PGF1 alpha], and PGE2 were measured in 15HbSS patients, eight HbAA non-haemolytic anaemic individuals and 12 healthy HbAA controls using specific RIAs. The mean urinary 2,3-dinor-TxB2 in the HbSS patients was significantly higher than in both the healthy HbAA and the anaemic controls. 6-keto-PGF1 alpha was undetected in the urines of the healthy HbAA controls, but was measured insignificant amounts in the HbSS and the HbAA anaemic patients. The urinary concentrations of PGE2 and TxB2 in HbSS patients' samples were also significantly higher than those of both control groups (P < 0.05). PGE2 and TxB2 levels were below the detection limit in the plasmas of the HbAA subjects, but were measurable in the HbSS and HbAA anaemic plasmas. The plasma level of 6-keto-PGF1 alpha in the HbSS patients was also significantly higher than in the control groups. The data indicates a persistent inflammatory process in the HbSS patients, and is consistent with the hypothesis that there is platelet and endothelial cell activation in SCD.
authors.affiliation: Department of Physiology, George Washington University Medical Center, Washington, D.C. 20037.
authors.forename: J
authors.initials: J
authors.lastname: Kurantsin-Mills
authors.forename: B O
authors.initials: BO
authors.lastname: Ibe
authors.forename: C L
authors.initials: CL
authors.lastname: Natta
authors.forename: J U
authors.initials: JU
authors.lastname: Raj
authors.forename: R S
authors.initials: RS
authors.lastname: Siegel
authors.forename: L S
authors.initials: LS
authors.lastname: Lessin
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000652:urine; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000378:metabolism* / Q000652:urine; D001792:Blood Platelets / Q000378:metabolism*; D015232:Dinoprostone / Q000097:blood / Q000652:urine*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine
chemical_list: D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C028965:2,3-dinor-thromboxane B2; D015232:Dinoprostone