Fibrinogen Cleveland II AN ABNORMAL FIBRINOGEN WITH DEFECTIVE RELEASE OF FIBRINOPEPTIDE A EDWARD

were all prolonged. 16 of 24 tested relatives had the defect, which appeared to be transmitted as an autosomal dominant characteristic. The thrombin time of normal plasma was slightly inhibited by the proband's plasma. The abnormally long thrombin time of fibrinogen Cleveland II was partially corrected by addition of calcium ions. Fibrinogen Cleveland II was indistinguishable from normal fibrinogen by immunoelectrophoresis, DEAE-cellulose column chromatography, or polyacrylamide gel electrophoresis of reduced fibrinogen in sodium dodecyl sulfate. The major defect detected appeared to be impaired release of fibrinopeptide A when fibrinogen Cleveland II was incubated with thrombin. This defect was localized to the NH2-terminal disulfide knot portion of the molecule. An abnormality of polymerization of fibrin monomers was also present, but the abnormal fibrin demonstrated relatively normal crosslinking. Despite these defects, fibrinogen Cleveland II achieved a degree of coagulability similar to normal fibrinogen and appeared to incorporate some molecules of fibrin with intact fibrinopeptide A into the clot. The fibrin clot that was formed appeared to be abnormal by This work has appeared previously as an abstract: Crum, E. D., J. R. Shainoff, and 0. D. Ratnoff. 1973. Fibrinogen Cleveland II. Clin. Res. 21: 550. Dr. Graham is the recipient of an N.I.H. Career Development Award, AM 42397. Dr. Ratnoff is a Career Investigator of the American Heart Association. Received for publication 21 September 1973 and in revised form 13 December 1973. electron microscopy. These functional defects and other descriptive characteristics appear to distinguish fibrinogen Cleveland II from other inherited abnormal fibrinogens.