1640 PROSTACYCLIN DEFICIENCY DOES NOT PLAY A PIVOTAL ROLE IN HEMOLYTIC UREMIC SYNDROME (HUS)

Abstract

A decrease in the prostacyclin (PGI2) stimulating activity of plasma has been reported in children with HUS. Although no study has attempted to assess plasma PGI2 levels themselves, the presence of a decrease in the PGI2 stimulating activity has been equated with a deficiency of PGI2 in HUS. We have conducted an evaluation of plasma prostanoids (PGI2 and TXB2) in 5 children admitted to SUNY during an epidemic of HUS in the northeast and in 23 controls. We were unable to document a pivotal role for PGI2 deficiency in HUS. Using an RIA for plasma 6KPGF1α(the stable hydrolysis product of PGI2), patients with HUS demonstrated elevated 6KPGF1α levels of 1.05±0.3 (1SD) pmol/ml when compared to controls (0.41±0.13; p<0.001). Increased production of PGI2 in HUS was accompanied by a concomitant increase in plasma thromboxane. Compared to a plasma TXB2 level of 0.10±0.06 in controls, the mean level in patients with HUS was 0.33±0.09pmol/ml (p<0.001). When the ratio of plasma TXB2 to 6KPGF1α was evaluated as an index of proaggregatory and vasoconstrictor versus antiaggregatory and vasodilator influences, no difference was observed between controls (0.33±0.06) and HUS (0.33±0.08). Changes in prostanoid production in HUS appear to reflect vascular injury (T6KPGF1α) and concomitant platelet consumption (↑TXB2). A deficiency of PGI2 in HUS was an attractive hypothesis that explained the systemic hypertension and the observed thrombocytopenia. Our finding however does not support a role for prostacyclin deficiency, and underscores the heterogenousness of HUS.