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

Summary . The molecular weight heterogeneity of fibrinogen from the whole plasma of 12 normal and seven cirrhotic individuals was examined by means of a novel two-dimensional sodium dodecyl sulphate (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 Aα, Bβ and γ chains on a second gel. Fibrinogen was resolved into two major bands, I and II, on the first gel. The ratio of fibrinogen II to fibrinogens I plus II was approximately 0.3 (range 0.2-0.35) for both normals and cirrhotic patients. Two major molecular weight (mol wt) forms of Aα chain were present in normal fibrinogen I: Aα/I and/or Aα/2, mol wt 7 × 10⁴ and 6.7 × 10⁴ respectively. Normal fibrinogen II contained either one of these Aα chains plus one of the smaller Aα chains, Aα/6-10, accounting for the 3–4 × 10⁴ mol wt difference between bands I and II. Aα/2 comprised 33% of the total Aα chains (range 27–41%) in normal fibrinogen I and approximately 25% of the Aα chains in normal fibrinogen II. In contrast, fibrinogen I from six out of the seven patients contained a lower percentage of Aα/2 (range 10–25%). Similarly fibrinogen II from these patients was deficient in Aα/2, although the protein contained normal levels of lower mol wt Aα derivatives. No correlation was found between per cent fibrinogen II and per cent Aα/2 in either normal or cirrhotic subjects. These results suggest that at least two independent processes are responsible for the observed levels of Aα heterogeneity in normals and cirrhotics and that the process controlling Aα/2 production is abnormal in cirrhotic individuals. This decrease in Aα/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.