Platelet and vascular prostaglandins in uraemia, thrombotic microangiopathy and pre-eclampsia

Abstract The metabolism of arachidonic acid in platelets and vascular cells is often altered in clinical conditions associated with haemorrhagic or thromboembolic complications. We have focused on the one hand on uraemia as a condition frequently complicated by bleeding episodes and, on the other, on thrombotic microangiopathy (thrombotic thrombocytopenic purpura, t.t.p.; haemolytic-uraemic syndrome, h.u.s.) and pre-eclampsia as conditions characterized by uncontrolled intravascular platelet activation. The observation that prostaglandin synthesis may be regulated by factors present in normal human plasma (Saeed et al. 1977; MacIntyre et al. 1978) prompted us to investigate whether such plasmatic control was altered in the clinical situations mentioned. Venous specimens removed from uraemic patients during the institution of an artero-venous shunt for haemodialysis generated significantly more prostacyclin (prostaglandin I2, PGI2) than control vessels (Remuzzi et al. 1977). Similar findings were subsequently reported in aortic tissue from nephrectomized rats and in arterial tissue from uraemic patients (Leithner et al. 1978). Uraemic plasma showed a greater capacity for stimulating PGI2 synthesis by vascular rings or endothelial cultured cells (Remuzzi et al. 1978; Defreyn et al. 1980).