An Abnormal Fibrinogen with Delayed Fibrinopeptide a Release

An investigation has been carried out of a coagulation defect occuring in three generations of a family as an autosomal dominant trait. Coagulation tests revealed a slightly elevated fibrinogen concentration, a normal FDP level yet prolonged thrombin clotting time, suggesting a congenital dysfibrinogenemia. Further plasma clotting studies demon strated no pH dependence of the defect, little correction by calcium ions, but a total correction when normal and patient plasma were mixed in equal amounts. A dysfibrinogenemla was confirmed when fibrinogen purified from plasma of one of the patients exhibited delayed clotting with thrombin. A small delay in the rate of polymerisation of monomers was evident when purified patient monomers were compared with those of normals. Electro-phoretic, immunoelectrophoretic and immunodiffusion experiments were able to detect neither structural nor immunological abnormalities associated with the intact molecule nor with the A α, Dβ, and γ chains of fibrinogen. Factor XIIIa induced cross linking of fibrin appeared normal as judged by SDS Polyacrylamide gel electrophoresis. However, using a specific radioimmunoassay to fibrinopeptide A the major defect has been Localised to a delay in the rate of release of this peptide by thrombin when the patient fibrinogen is converted to fibrin. The abnormality has been tentatively designated fibrinogen Manchester.