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Fib420 , the Novel Fibrinogen Subclass: Newborn Levels Are Higher Than Adult

Gerd Grieninger, Xianghan Lu, Yan Cao, Yiping Fu, Bohdan J. Kudryk, Dennis K. Galanakis, and Kathe M. Hertzberg

From the Lindsley F. Kimball Research Institute of the New York Blood Center, New York, NY; the Department of Pathology, SUNY at Stony Brook, NY.

Fib420 is a recently identified subclass of normal human fibrinogen in which two extended alpha  chain isoforms (alpha E ) replace the common alpha  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 Fib420 levels in normal, healthy adults and in placental cord (fetal) blood. For measuring Fib420 , 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 (n = 25 each; total fibrinogen ca. 2.6 mg/mL in both) revealed a statistically significant difference, with a mean level of 100 ± 28 µg/mL in the neonate compared to 34 ± 7 µg/mL in the adult. On average, 1 out of every 100 fibrinogen molecules in adult plasma belongs to the Fib420 subclass. Unlike in the newborn, adult Fib420 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 Fib420 subclass and a homeostatic control operating in later stages of life.

Blood, Vol. 90 No. 7 (October 1), 1997: pp. 2609-2614
© 1997 by The American Society of Hematology.


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