A 13-year-old girl with chronic aggressive hepatitis, postnecrotic cirrhosis, ulcerative colitis, and a coagulation defect acquired an antibody that specifically interfered with fibrin formation. We sought to characterize the antibody and determine the mechanism of its inhibitory activity. The patient's purified fibrinogen was functionally normal; however, the antibody inhibited the self-assembly of fibrin and prolonged the clotting times of the patient's plasma. This antibody, which belonged to the IgG class of immunoglobulins, acted early in the polymerization process to inhibit the association of fibrin monomers, as indicated by a prolonged lag time and a decreased slope in the polymerization curves. It did not inhibit fibrinopeptide cleavage or fibrin cross-linking. Affinity chromatography indicated that the antibody bound strongly to both fibrinogen and fibrin monomer.
SummaryHeterogeneity in human fibrinogen was examined using an improved two-dimensional isoelectric focusing-SDS polyacrylamide gel electrophoretic procedure. Four different preparations of fibrinogen were compared: single donor fibrinogen prepared from plasma by precipitation with ammonium sulfate or by affinity chromatography on fibrin-monomer Sepharose, fraction I—4 prepared from Cohn fraction I paste, and Kabi grade L. The subunit Aα, Bβ, and γ chains in all preparations had marked charge heterogeneity. The three chains were clearly separated from each other and a range of isoelectric points for each chain could be assigned. Minor variations in the subunit heterogeneity of the different preparations were found. Intermediates in the transition from fibrinogen to crosslinked fibrin were also examined. A striking increase in the heterogeneity of the α chain was observed during crosslinking.
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