THE DYSFIBRINOGEN OF CHILDHOOD NEPHROSIS

An abnormal fibrinogen (Fib) related to increased sialic acid (SA) has been described in adults with liver disease. This dysfibrinogen (Dysfib) seems most like fetal Fib. A review of 11 patients with nephrosis revealed an unexplained prolonged thrombin time (TT) and otherwise normal coagulation studies. Based on these observations, we sought to answer whether the prolonged TT defined a Dysfib and if this abnormal Fib was similar to fetal Fib. Pooled adult, fetal plasma, and the plasma of 3 patients with nephrosis were studied with TT and reptilase times (RT). Fib was measured by functional (Fib-act) and immunologic (Fib-ag) assays. An enzyme linked immunosorbent assay (ELISA) was established using antifibrinogen as the first antibody and either peroxidase conjugated Fib or a lectin (Limulus Polyphemus) specific for SA as the second antibody. The optical density was recorded per μgm Fib for both conjugated antifibrinogen or lectin and the ratio compared in order to estimate SA reactivity. Patient 3 was also studied by: 1) crossed immunoelectrophoresis (CIE) employing lectin in the first dimension and 2) polyacrylamide gel electrophoresis (PAGE) with transfer to nitrocellulose paper using Western Blot technique.Results of the CIE showed patient 3 and fetal plasma were similar in electrophoretic pattern and different from adult plasma. The PAGE with Western Blot revealed a similar pattern of Fib for patient 3, fetal and adult plasma. We conclude that the prolonged TT and RT, the greater amount of Fib-ag when compared to Fib-act in patients 1-3 and fetal plasma and the absence of evidence for Fib degradation products, support the diagnosis of Dysfib. The similarity of the CIE for patient 3 and fetal plasma and the difference between ELISA lectin/Fib ratio of patients 1-3 and fetal compared with adult plasma suggest that the Dysfib of nephrosis may be similar to fetal Fib.