title: Increased thromboxane biosynthesis in childhood hemolytic uremic syndrome.
abstract: Vascular endothelial cell damage plays a central role in the pathogenesis of the hemolytic uremic syndrome (HUS), resulting in intravascular platelet activation and thrombotic microangiopathy. A deficiency of the antiaggregatory prostacyclin (PGI2) has been postulated by experiments under ex vivo conditions. However, this observation has not been confirmed in vivo. The pathophysiological contribution of thromboxane (Tx)A2, a potent vasoconstrictor and platelet-aggregating prostanoid which is predominantly produced by platelets, has not been elucidated so far. In order to quantitate endogenous formation of TxA2 in children with HUS, plasma concentrations of the enzymatic metabolite 11-dehydro-TxB2 of TxA2 and urinary excretion rates of three major TxA2 metabolites, TxB2, 11-dehydro-TxB2 and 2,3-dinor-TxB2 were analyzed using gas chromatography/mass spectrometry. PGI2 biosynthesis was assessed by measuring urinary excretion of an index metabolite of its systemic production, 2,3-dinor-6-keto-prostaglandin (PG) F1 alpha, and an index of its renal production, 6-keto-PGF1 alpha. TxA2 biosynthesis was markedly elevated in the acute phase of HUS. This activation could be detected for a longer period of time than the presence of thrombocytopenia. Concomitantly in the acute phase, renal PGI2 formation was significantly elevated and systemic PGI2 formation was elevated in 50% of the patients. These data indicate that TxA2 formation is increased in the acute phase in patients with HUS. This enhanced biosynthesis is consistent with increased platelet activation, whereas the increased PGI2 biosynthesis reflects predominantly renal endothelial cell damage.
authors.affiliation: Children's Hospital of the University of Heidelberg, Federal Republic of Germany.
authors.forename: B
authors.initials: B
authors.lastname: Tönshoff
authors.forename: R
authors.initials: R
authors.lastname: Momper
authors.forename: P G
authors.initials: PG
authors.lastname: Kühl
authors.forename: H
authors.initials: H
authors.lastname: Schweer
authors.forename: K
authors.initials: K
authors.lastname: Schärer
authors.forename: H W
authors.initials: HW
authors.lastname: Seyberth
mesh_terms: D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007223:Infant; D008297:Male; D015539:Platelet Activation; D011453:Prostaglandins / Q000652:urine; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine
chemical_list: D011453:Prostaglandins; D013929:Thromboxane B2; D013928:Thromboxane A2; C028965:2,3-dinor-thromboxane B2; C049235:11-dehydro-thromboxane B2; D003404:Creatinine; D011464:Epoprostenol