Nephrotic Syndrome (NS): Evidence for Increased Platelet Prostaglandin Synthesis.

 

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NS is associated with an increased incidence of arterial and venous thrombosis. Hemostasia was evaluated in 11 children with NS (6 with active disease Grp I, and 5 in remission Grp II). Studies included assays for fibrinogen, FDP, Antithrombin III (AT III), platelet count and aggregations. Platelet malonyldialdehyde (MDA) in the presence of N-ethyl maleimlde (NEM) or thrombin was used as an indicator of endoperoxide formation, and platelet survivals were performed in 3/11. Platelet hyperaggregability was present in Grp I and was associated with significantly increased platelet MDA in the presence of both NEM (4.0 ± 0.29), or thrombin (1.77 ± 0.32) compared to normal controls (3.20 ± 0.26; 1.26 ± 0.18). Other evidence for a “hypercoagulable” state included a marked reduction in plasma AT III levels to 9.4 ± 3.8 (controls 24 ± 3 mg/100 ml), and a reduction in platelet life-span in both children in Grp I in whom this study was performed (T½ of 2.1 and 2.5 days). Grp II patients did not demonstrate platelet hyperaggregability and platelet MM was normal (3.21 ± 0.4; 1.13 ± 0.19). AT III levels were normal at 26.5 ± 4.8 mg/100 ml, and platelet life-span was normal in 2/2 children (T½ of 3.6 and 4.4 days). The normal half-life of 4.4 days was obtained in the same child in whom a T½ of 2.5 days was present during active disease. Since a reduction in platelet survival is associated with an increased risk of thromboembolism in a number of pathological states, this finding is of clinical significance and may identify the patient with NS who is at risk. Platelet hyperaggregability in this syndrome is prostaglandin related, and appears to be due to an increase in platelet endoperoxide formation.