Dysfibrinogenaemia characterized by abnormal fibrin monomer polymerization and normal fibrinopeptide A release.
Routine testing on plasma from a patient due to undergo a coronary artery bypass graft operation revealed a prolonged thrombin clotting time associated with a normal plasma fibrinogen level when this was determined by a method not dependent upon the rate of fibrin formation. Fibrinogen purified from the patient's plasma by precipitation with beta-alanine also gave a prolonged thrombin time and this confirmed the presence of a dysfibrinogenaemia. Increasing calcium chloride concentration, addition of protamine sulphate and decreasing ionic strength all produced a partial correction of the clotting defect. Addition of normal plasma to patient's plasma failed to correct the prolonged thrombin clotting time and a pH dependence of the defect was also observed. Kinetic studies of fibrinopeptide release, using a specific radioimmunoassay, demonstrated no delay in the release of patient fibrinopeptide A. The functional defect was localized as an abnormality in the polymerization of fibrin monomers by studying fibrin monomers prepared and isolated from plasma and from purified fibrinogen solution. An electrophoretic examination of the patient's fibrinogen using both agarose and polyacrylamide gels failed to demonstrate any alteration in mobility or any structural defect associated with the polypeptide chains A alpha, B beta and gamma. All seven of the living siblings of the propositus and also his daughter showed no abnormality in any clotting assay. However, because the propositus did not suffer from liver disease it has been assumed that the abnormality is genetic in origin.
D000328:Adult; D001778:Blood Coagulation Disorders / Q000097:blood / Q000235:genetics*; D001780:Blood Coagulation Tests; D004591:Electrophoresis, Polyacrylamide Gel; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D005779:Immunodiffusion; D007122:Immunoelectrophoresis; D046911:Macromolecular Substances; D008297:Male; D010375:Pedigree; D013917:Thrombin / Q000378:metabolism
D046911:Macromolecular Substances; D005344:Fibrinopeptide A; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin