THE PROLONGED THROMBIN TIME OF NEPHROTIC SYNDROME

Purpose: Little information is available that documents the incidence and possible etiology of a prolonged thrombin time (TT) found in child ren with nephrotic syndrome. We speculated that this prolonged TT migh t best be explained by an altered fibrinogen similar to that found in the newborn. Patients and Methods: We describe 20 children with nephro sis, an unexplained prolonged TT and reptilase lime (RT), and an eleva ted fibrinogen level. Thrombin and/or plasmin effect on plasma fibrino gen was studied by analyzing for soluble monomer, D-dimer, fibrin degr adation products, B beta 1-42 peptide, and by polyacrylamide gel elect rophoresis (PAGE) and agarose electrophoresis. Structural changes in t he fibrinogen molecule were investigated using two- dimensional gel (2 D gel) electrophoresis. Fibrinogen was purified via glycine precipitat ion, and the sialic acid (SA) content was determined. Results: No evid ence for in vivo thrombin and/or plasmin effect on fibrinogen could be detected in 13 of 20 children tested. Additionally, no fibrin/fibrino gen degradation products or soluble fibrin complexes were detected usi ng PAGE or agarose electrophoresis in this group of patients. The B be ta isoforms of nephrosis fibrinogen were similar in isoelectric point on 2D gel electrophoresis to those of fetal fibrinogen and demonstrate d a greater electronegative shift when compared with normal adult Fibr inogen. Also, the SA content of nephrosis and fetal fibrinogen were gr eater than that measured in adult fibrinogen. Both nephrosis and fetal fibrinogen were more resistant to neuraminidase treatment than was no rmal adult fibrinogen. Conclusions: These data support the notion that an altered fibrinogen exists in some children with nephrotic syndrome characterized by an increased TT and RT, elevated fibrinogen, and bot h an increased negative charge and SA content.