Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease

To evaluate the possibility that the carbohydrate composition of fibrinogen may be altered in the dysfibrinogenemia associated with liver disease, we studied the sialic acid content of purified fibrinogen from 12 patients with liver disease and its relationship to the prolongation of the thrombin time. Purified fibrinogen showed that Aalpha-, Bbeta-, and gamma-chains when reduced and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and exhibited prolongation of the thrombin time similar to that of the plasma from which it was derived. Sialic acid content of the purified fibrinogen ranged from 12.7 to 71.4% higher in patient fibrinogens when compared to normal controls. A progressive delay in thrombin time was associated with increasing sialic acid content of the patient fibrinogen. Enzymatic removal of sialic acid from four of the abnormal fibrinogens resulted in a shortening of their thrombin times to the range of the desialylated normal control. Periodic acid-Schiff reagent stained only the Bbeta- and gamma-chains of the reduced patient fibrinogens after sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting that the excess sialic acid is located on these two chains. These studies demonstrate a biochemical alteration of the functionally abnormal fibrinogen found in some patients with liver disease, and indicate that the excess sialic acid plays an important role in the functional defect of this protein.