Functional Evaluation of an Inherited Abnormal Fibrinogen: Fibrinogen "Baltimore"

A B S T R A C T The rate of clotting and the rate of de-velopment and degree of turbidity after addition of thrombin to plasma or purified fibrinogen from a patient with fibrinogen Baltimore was delayed when compared with normal, especially in the presence of low concen-trations of thrombin. Optimal coagulation and develop-ment of translucent, rather than opaque, clots occurred at a lower pH with the abnormal fibrinogen than with normal. Development of turbidity during clotting of the abnormal plasma or fibrinogen was less than normal at each pH tested, but was maximal in both at approxi-mately pH 6.4. The physical quality of clots formed from fibrinogen Baltimore was abnormal, as demon-strated by a decreased amplitude on thromboelastog-raphy. The morphologic appearance of fibrin strands formed from fibrinogen Baltimore by thrombin at pH 7.4 was abnormal when examined by phase contrast or electron microscopy, but those formed by thrombin at pH 6.4 or by thrombin and calcium chloride were simi-lar to, though less compact, than normal fibrin. The periodicity of fibrin formed from fibrinogen Baltimore was similar to normal and was 231-233 A. A study of the release of the fibrinopeptides from the patient's fibrinogen and its chromatographic subfractions verified the existence of both a normally behaving and a defective form of fibrinogen in the patient's plasma. The defective form differed from normal in three func-tionally different ways: (a) the rate of release of fibrin-opeptides A and AP was slower than normal; (b) no visible clot formation accompanied either partial or com-Dr. Beck was a recipient of U. S. Public Health Servic