Quantitative Abnormality of an Aα Chain Molecular Weight Form in the Fibrinogen of Cirrhotic Patients

Publisher Website
Google Scholar
Abstract
The MW heterogeneity of fibrinogen from the whole plasma of 12 normal and 7 cirrhotic individuals were examined by a novel 2-dimensional sodium dodecyl sulfate (SDS) gel electrophoretic technique. Fibrinogen was first separated from other plasma proteins on a large pore gel, cut out of the gel, reduced and separated into its component A.alpha., B.beta. and .gamma. chains on a 2nd gel. Fibrinogen was resolved into 2 major bands, I and II, on the 1st gel. The ratio of fibrinogen II to fibrinogens I plus II was approximately 0.3 (range 0.2-0.35) for normals and cirrhotic patients. Two major MW forms of A.alpha. chain were present in normal fibrinogen I: A.alpha./1 and/or A.alpha./2, MW 7 .times. 104 and 6.7 .times. 104, respectively. Normal fibrinogen II contained either one of these A.alpha. chains plus one of the smaller A.alpha. chains, A.alpha./6-10, accounting for the 3-4 .times. 104 MW difference between bands I and II. A.alpha./2 comprised 33% of the total A.alpha. chains (range 27-41%) in normal fibrinogen I and approximately 25% of the A.alpha. chains in normal fibrinogen II. Fibrinogen I from 6 out of the 7 patients contained a lower percentage of A.alpha./2 (range 10-25%). Similarly fibrinogen II from these patients was deficient in A.alpha./2, although the protein contained normal levels of lower MW A.alpha. derivatives. No correlation was found between percent fibrinogen II and per cent A.alpha./2 in normal or cirrhotic subjects. At least 2 independent processes are apparently responsible for the observed levels of A.alpha. heterogeneity in normals and cirrhotics and the process controlling A.alpha./2 production is apparently abnormal in cirrhotic individuals. This decrease in A.alpha./2 does not affect the coagulability of fibrinogen. Fibrin monomer aggregation studies indicate that a serum component is, in part, responsible for the abnormally transparent clot formed from the plasma of cirrhotics.