Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF

Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF. In a double-blind, randomized, placebo-controlled cross-over study, we investigated in seven patients with chronic renal failure the effect of conjugated estrogens (0.6 mg/kg/day for 5 days) on template bleeding time and on thromboxane A 2 (TxA 2 ), β-thromboglobulin (β-TG) and prostacyclin (PGI 2 ) concentrations in blood emerging from the template bleeding time incisions. Administration of conjugated estrogens resulted in a significant shortening of the bleeding time in six out of seven patients with a maximum effect 7 and/or 14 days following treatment. Both TxA 2 (measured as thromboxane B 2 , TxB 2 ) and β-TG release in bleeding time blood were significantly higher following administration of conjugated estrogens as compared to placebo administration. No difference was seen in endothelial PGI 2 (measured as 6-keto-prostaglandin F 1α ) formation when patients were treated with conjugated estrogens as compared to placebo administration over the 28 day observation period. We conclude that in patients with chronic renal failure, infusion of conjugated estrogens results in a significant shortening of the bleeding time together with an increase in platelet reactivity, as indicated by an increase of TxA 2 and β-TG concentration in the microvasculature. No effect was seen on PGI 2 production, thereby excluding a major effect on vascular prostaglandin metabolism.