Studies of platelet fibrinogen from a subject with a congenital plasma fibrinogen abnormality (fibrinogen Paris I)

Abstract

Abstract Fibrinogen from normal platelets and plasma was compared with material derived from a subject with the congenital fibrinogen abnormality termed fibrinogen Paris I. The molecular abnormality in this subject is characterized by the presence (in plasma molecules) of relatively large mutant γ-chains (γ-Paris I) that replace 50% or more of the normal γ-chain population and that, unlike normal γ-chains, do not form covalently linked γ-dimers in the presence of plasma transglutaminase (factor XIIIa). Extracts of washed or washed and trypsin-treated platelets that had been lysed in the presence of 8 M urea were subjected to CM-cellulose chromatography in the presence of 8 M urea. The fibrinogen-containing chromatographic peak from each sample was then concentrated and analyzed by dodecyl sulfate gel electrophoresis. All unreduced samples (5% polyacrylamide gels) possessed a fibrinogen band migrating in the same position as plasma fibrinogen. Unstained gel slices containing platelet fibrinogen were reduced with dithiothreitol and again subjected to dodecyl sulfate gel electrophoresis (10% polyacrylamide gels). All such samples showed bands corresponding in position and in relative staining intensity to the Aα, Bs, and γ-chains of normal plasma fibrinogen, findings confirming the observation that platelet fibrinogen is not significantly different in size from that in plasma. The band corresponding to the γ-Paris I chain was not observed in any sample. The absence of mutant γ-chains from platelet fibrinogen molecules derived from the Paris I subject is confirmatory evidence that platelet and plasma fibrinogen pools are separate from one another. The results also indicate that the subject's platelet and plasma fibrinogens, at least as far as their γ-chains are concerned, are not assembled from identical gene products. It remains to be shown whether this finding reflects a more general situation regarding hepatic and platelet fibrinogen from normal individuals.