Fibrinogen Adelaide: a familial hypodysfibrinogenaemia associated with abnormal alpha chains

A familial hypodysfibrinogenaemia occurring in four females with occasional haemorrhagic problems in an Adelaide family was investigated. Affected family members had slightly prolonged thrombin time, prothrombin time and Reptilase time tests, and apparently elevated levels of fibrin degradation products (FDPs). Fibrinogen assessed by reactivity with thrombin (Clauss method) was significantly less than fibrinogen determined by various other methods, though even by immunoquantitation fibrinogen levels were only slightly above half normal in affected family members. Isoelectric focussing (IEF) of the reduced patient's fibrinogen in urea/polyacrylamide gel revealed minor components with higher isoelectric points (pI) than present in normal fibrinogen or fibrin. These were shown to have a molecular weight similar to the alpha chain of fibrin by subsequent sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The abnormal species tended to remain in plasma after clotting with Reptilase or thrombin although polymerization of the clotted fibrin was normal. The magnitude of the pI shift relative to normal fibrin alpha chain indicated an increased positive charge on the abnormal species.