Inherited hypodysfibrinogenemia (fibrinogen Bern I) was found in four members (two
generations) of a family with no haemorrhagic or thrombotic history. Fibrin aggregation
curves (350 nm, 37°C) with patient plasma or purified fibrinogen Bern I, after addition
of thrombin, were normal at high calcium concentrations (5mM) but delayed at lower
calcium concentrations (≤0.lmM). The release of fibrinopeptide A was normal. Whereas
the polypeptide chains of fibrinogen Bern I were indistinguishable from normal fibrinogen
by SDS-gel-electrophoresis, an abnormal γ-chain with a decreased negative charge was
found by isoelectric focussing.
Plasmic degradation o| normal fibrinogen, in the presence of calcium (≥ImM), results
in only one terminal D fragment which is stabilized by calcium against further degradation
of γ-chains. In contrast, degradation of fibrinogen Bern I, under the same conditions,
yielded at least two additional smaller D fragments. In conclusion, fibrinogen Bern
I is characterized by defective calcium binding in the D domain of the γ-chain.
