Fib(420), the novel fibrinogen subclass: Newborn levels are higher than adult

Fib(420) is a recently identified subclass of normal human fibrinogen in which two extended alpha chain isoforms (alpha(E)) replace the common a chains, yielding a molecule (ca. 420 kD) which is larger than the more abundant 340-kD form. Evidence for preservation of this subclass throughout vertebrate evolution suggests it performs some as yet unidentified vital function. A survey was undertaken to establish the range of plasma Fib(420) levels in normal, healthy adults and in placental cord (fetal) blood. For measuring Fib(420), a quantitative Western blot assay was developed using monoclonal antibody against the exon-VI encoded C-terminus of the molecule's unique alpha(E) chain. This alpha(E) chain signal was normalized to that of the beta chain, common to both fibrinogen forms. Analysis of plasma samples from the adult and newborn cohorts in = 25 each; total fibrinogen ca. 2.6 mg/mL in both) revealed a statistically significant difference, with a mean level of 100 +/- 28 mu g/mL in the neonate compared to 34 +/- 7 mu g/mL in the adult. On average, 1 out of every 100 fibrinogen molecules in adult plasma belongs to the Fib(420) subclass. Unlike in the newborn, adult Fib(420) levels remained the same over a wide range of total plasma fibrinogen. The striking difference observed between these two cohorts suggests a changing developmental expression of the Fib(420) subclass and a homeostatic control operating in later stages of life. (C) 1997 by The American Society of Hematology.