We report on three unrelated individuals with the same uncommon type of dysfibrinogenemia,
originating from Bergamo, Essen and Perugia. None of them showed bleeding symptoms
while the Bergamo patient and members of her family presented with a thrombotic tendency.
The presence of a defective fibrinogen was suggested by prolonged thrombin and rep-tilase
times. Furthermore, fibrinogen concentrations of less than 0.28 g/L were determined
by the functional assay whereas values of 1.5-2.4 g/L were measured by heat precipitation
or electroimmunoassay. Fibrinogen was isolated by affinity chromatography on insoluble
fibrin monomer. The rate of fibrinopeptide release by thrombin was normal while the
fibrin polymerization reaction was strongly delayed. An abnormal peptide (γ265-310)
was isolated by high-performance liquid chromatography after cyanogen bromide cleavage
of the purified γ-chain of fibrinogen Bergamo II and Essen. The same peptide was also
isolated following cyanogen bromide treatment of the intact fibrinogen Perugia. Sequence
analyses of these peptides demonstrated the same amino acid exchange in all three
fibrinogens: γ275 arginine → histidine. The described fibrinogen variants appear to
possess a molecular defect which has thus far only been observed in fibrinogen Haifa.
Key words
Dysfibrinogenemia - Fibrinogen Essen - Fibrinogen Bergamo II - Fibrinogen Perugia
