Familial Deficiency of a Plasma Factor Stimulating Vascular Prostacyclin (PGI2) Activity

We previously reported successful treatment with plasma in patients with thrombotic micro angiopathy and defective vascular PGI2 activity and suggested that a defect in a plasma factor stimulating PGI2 synthesis might be implicated in the pathogenesis. We report here that in one of these patients the plasma defect was still detectable 1 year after clinical remission (without recurrencies). Two of this patient’s 4 children had a simile,though less severe, plasma defect. The proposita is a 54-year-old woman admitted with a clinical and laboratory picture of haemolytic uraemic syndrome. Unlike normal plasma, the patient’s plasma had a low capacity to stimulate PGI2 production by rat aortic rings (previously washed until their endogenous PGI2 activity was exhausted). After plasma treatment the patient’s plasma behaved normally in this respect, but again appeared deficient at outpatient follow-up. PGI2 stimulating activity was normal in 2 daughters but consistently low (20-60% of control) in both patient’s sons. None of them had any history or clinical signs of microangiopathic disorders. Detection of this plasma defect in apparently healthy subjects and in patients who have recovered from thrombotic microangiopathic episodes could have clinical implications. Our observations support previous suggestions that some people have a congenital (or hereditary) predisposition to thrombotic microangiopathy. (Supported by Ass. Berg. Mal. Ren. and Italian CNR, Rare disease Project).