Abstract
ABSTRACT: Plasma levels of 6-keto-prostaglandin F1α (6kPGF1α) and thromboxane (Tx) B2 have been assessed in sickle cell disease (SCD) with discrepant results. Inasmuch as direct measurement of plasma prostanoids is fraught with the problem of interfering substances, we assessed plasma 6kPGF1α and TxB2 levels in patients with SCD by RIA after extraction of eicosanoids and separation by HPLC. We demonstrate that the 6kPGF1α and TxB2 levels in children with SCD in steady state as well as in vaso-occlusive crisis (VOC) are significantly lower when compared with those from age-matched controls. The VOC plasma 6kPGF1α and TxB2 levels were, however, significantly elevated when compared with those from children in steady state. Changes similar to those noted with unpaired plasma samples were also observed when paired steady state and VOC plasmas from the same patients were assessed. The ratio of TxB2 to 6kPGF1α, was, however, significantly elevated in patients with SCD in crisis when compared with eicosanoid ratios obtained during steady state. In an attempt to understand whether the abnormality in 6kPGF1α was due to an impairment in endothelial cell prostacyclin-regenerating ability, we compared the ability of plasma from controls and children with SCD to activate arachidonic acid (AA) release and prostacyclin production by [14C]AA-prelabeled bovine aortic endothelial cells. Our results suggest that the decreased 6kPGF1α levels in plasma from children with SCD was not due to an effect on substrate AA release but rather a modulatory effect of sickle plasma components on endothelial cell cyclooxygenase activity. Although a decreased production of prostacyclin has previously been suggested to play a role in the initiation and/or propagation of vaso-occlusion in SCD, our study demonstrates a relative increase during VOC of 6kPGF1α levels over those observed in steady state. However, the rise in 6kPGF1α is accompanied by an increase in levels of TxB2 such that the ratio of TxB2 to 6kPGF1α is significantly increased during VOC. The imbalance in the production of vasoactive eicosanoids, TxA2 and prostacyclin, could potentially play a role in the potentiation of VOC in patients with SCD.
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Yamaja Setty, B., Chen, D. & Stuart, M. Sickle Cell Vaso-occlusive Crisis Is Associated with Abnormalities in the Ratio of Vasoconstrictor to Vasodilator Prostanoids. Pediatr Res 38, 95–102 (1995). https://doi.org/10.1203/00006450-199507000-00017
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DOI: https://doi.org/10.1203/00006450-199507000-00017
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