A New Case Of Dysfibrinogenemia : Isolation Of The Abnormal, Unclottable Fibrinogen Population
In a 81-year-old healthy woman, gross abnormalities of fibrin formation in routine tests led to the discovery of a dysfibrinogenemia.Abnormal and control fibrinogens were purified in parallel using precipitation by glycine (Kazal) ; final clottability was 95-98 % for the control and 50 % for the patient’s fibrinogen. Electrophoretic behaviour of the fibrinogen momecule, the three chains and the products of fibrin cross-linking by factor XIII a was normal. Functional studies gave the following results : (i) delayed coagulation by thrombin, Reptilase and Venacil with gross abnormalities of the clot; (ii) inhibition of coagulation of normal fibrinogen ; (iii) poor fibrin monomer aggregation (opacimetry) ; (iv) delayed fibrinogen proteolysis by plasmin (SDS-PAGE) . Release of fibrinopeptide A by thrombin was incomplete (RIA).Fibrinogen NH2-terminal residues were found normal, but the presence of ALA-residue in fibrin clot and in the supernatant showed that part of fibrinogen was not clotted, either copolymerized with fibrin or remaining in solution. Gel filtration of the supernatant showed the presence of both soluble complexes and fibrinogen characterized by the elution volume of the peak and NH2-terminal analysis. This fibrinogen population was unclottable by thrombin and inhibited clotting of normal fibrinogen.These preliminary results suggest the existence of a defect on the A-a chain of this abnormal fibrinogen which was called fibrinogen Bondy.