Nephrotic syndrome: increased platelet prostaglandin endoperoxide formation, hyperaggregability, and reduced platelet life span. Reversal following remission.

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Summary: Nephrotic syndrome is associated with an increased incidence of arterial and venous thrombosis. Platelet function was evaluated in 6 children with active disease (group I) and in 5 children in remission (group II). Platelet malonyldialdchyde in the presence of N-ethyl maleimide (1 mM) or thromhin (0.5 unit/ml) was used as an indicator of platelet prostaglandin endoperoxide formation in all patients evaluated, and platelet survivals were performed in 3 of 11. Platelet hyperaggregability was present in group 1 and was associated with a significant increase (P < O.001) in platelet MDA formation in the presence of either N-ethyl maleimide [4.0 ± 0.29 (1 S.D.) nmoles/109 platelets] or thrombin (1.77 ± 0.32) when compared to normal controls (3.20 ± 0.26: 1.26 ± 0.18). Other evidence for a “hypercoagulable” state included a marked reduction (P < 0.001) in plasma antithrombin III levels to 9.4 ± 3.8 mg/dl (controls, 24 ± 3) and a reduction in platelet life span in both children in whom this study was performed (half-life of 2.1 and 2.5 days), Group II patients in remission did not demonstrate platelet hyperaggregability. and platelet malonyldialdehyde was normal (3.21 ± 0.4; 1.13 ± 0.19). Antithrombin III levels were normal (26.5 ± 4.8), and platelet life-span was normal in both (iroup II children in whom this parameter was measured (half-life of 3.6 and 4.4 days). The normal half-life of 4.4 days was obtained in the same child in whom a half-life of 2.5 days was present during active disease. Platelet hyperaggregability in this syndrome appears to be due to increased prostaglandin endoperoxide synthesis. Inasmuch as a reduction in plasma antithrombin HI levels predisposes to thrombosis and a decrease in platelet survival has been documented to increase the risk of (hromboembolism in a number of pathologic states, these findings appear to be of importance in the etiology of hypercoagulability associated with nephrotic syndrome. Speculation: Platelet hyperaggregability and increased prostaglandin endoperoxide formation is seen in the nephrotic syndrome during disease activity. This platelet hyperfunctional state does not appear to be solely due to concomitant hypoalbuminemia. Other possible factors include a young, reactive platelet population with enhanced functional and thrombogenic potential or the presence of hypercholesterolemia which can he associated with platelet hyperaggregability (25). Antiplatelet aggregating agents have been used therapeutically in various disease states associated with a shortened platelet life span and an increased risk of thromboembolic complications. These agents may prove to be beneficial in decreasing the incidence of thromboembolic disease in children with the nephrotic syndrome.