Accelerated prostacyclin degradation in the thrombotic thrombocytopenic purpura.
Plasma prostacyclin (PGI2) degradation rate was measured in a 39-year-old man with chronic thrombotic thrombocytopenic purpura (TTP). His disease responded to plasma exchange, or plasma infusion alone, given at 3-4 week intervals. Plasmapheresis with albumin replacement had an adverse effect. PGI2 degradation rate was measured by incubation of exogenous PGI2 with plasma at 37 degrees C and recording of PGI2 activity after one, five, and fifteen min incubation  by measurement of inhibition of platelet aggregation. The PGI2 degradation rate of the patient was significantly higher than that of normal subjects. The degradation rate improved after each plasma treatment and correlated well with clinical improvement. Moreover, the degradation rate of PGI2 could be corrected in vitro by the addition of normal plasma. When the patients plasma was incubated with aortic rings, PGI2 activity was reduced but the level of its inactive end product, 6-keto-PGF1 alpha, was normal. These findings indicate that our patient had normal PGI2 stimulating activity but had an abnormal rate of PGI2 degradation. Accelerated PGI2 degradation which leads to PGI2 deficiency may be important in the pathogenesis of microvascular thrombosis.
D000328:Adult; D002908:Chronic Disease; D011464:Epoprostenol / Q000172:deficiency* / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008297:Male; D010951:Plasma Exchange; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000172:deficiency* / Q000378:metabolism*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000209:etiology* / Q000628:therapy
D011453:Prostaglandins; D011464:Epoprostenol