The prolonged thrombin time of nephrotic syndrome.
OBJECTIVE
Little information is available that documents the incidence and possible etiology of a prolonged thrombin time (TT) found in children with nephrotic syndrome. We speculated that this prolonged TT might best be explained by an altered fibrinogen similar to that found in the newborn.


METHODS
We describe 20 children with nephrosis, an unexplained prolonged TT and reptilase time (RT), and an elevated fibrinogen level. Thrombin and/or plasmin effect on plasma fibrinogen was studied by analyzing for soluble monomer, D-dimer, fibrin degradation products, B beta 1-42 peptide, and by polyacrylamide gel electrophoresis (PAGE) and agarose electrophoresis. Structural changes in the fibrinogen molecule were investigated using two-dimensional gel (2D gel) electrophoresis. Fibrinogen was purified via glycine precipitation, and the sialic acid (SA) content was determined.


RESULTS
No evidence for in vivo thrombin and/or plasmin effect on fibrinogen could be detected in 13 of 20 children tested. Additionally, no fibrin/fibrinogen degradation products or soluble fibrin complexes were detected using PAGE or agarose electrophoresis in this group of patients. The B beta isoforms of nephrosis fibrinogen were similar in isoelectric point on 2D gel electrophoresis to those of fetal fibrinogen and demonstrated a greater electronegative shift when compared with normal adult fibrinogen. Also, the SA content of nephrosis and fetal fibrinogen were greater than that measured in adult fibrinogen. Both nephrosis and fetal fibrinogen were more resistant to neuraminidase treatment than was normal 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 both an increased negative charge and SA content.
Abshire
T C
TC
Department of Pediatrics, Keesler Medical Center, Keesler AFB, Mississippi 39534-2520, USA.
Fink
L K
LK
Christian
J
J
Hathaway
W E
WE
D000328:Adult; D001780:Blood Coagulation Tests; D002648:Child; D015180:Electrophoresis, Gel, Two-Dimensional; D005337:Fibrin / Q000032:analysis; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005341:Fibrinolysin / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D019158:N-Acetylneuraminic Acid; D009404:Nephrotic Syndrome / Q000097:blood*; D011446:Prospective Studies; D012794:Sialic Acids / Q000032:analysis; D013917:Thrombin / Q000032:analysis; D013918:Thrombin Time
D005338:Fibrin Fibrinogen Degradation Products; D012794:Sialic Acids; C011468:fibrinmonomer; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin; D005341:Fibrinolysin; D019158:N-Acetylneuraminic Acid