Dysfibrinogenemia Associated with Liver Disease

Abstract

A B S T R A CT To test the possibility that a functionally abnormal fibrinogen may exist in some patients with liver disease, we studied the plasma and purified fibrinogens of five patients whose plasma thrombin times were prolonged at least 40% over normal controls. In no patient was there evidence of disseminated intravascular coagulation and/or fibrinolysis. No abnormalities were detected by immunoelectrophoresis of plasmas or purified fibrinogens. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reduced patient fibrinogens showed normal mobility and amount of Aa, B,3, and y chains. Alkaline polyacrylamide gel electrophoresis and gradient elution, DEAEcellulose chromatography of admixtures of radioiodinated patient 125I-fibrinogen and normal 1311-fibrinogen showed identical mobility in the gel and simultaneous elution from the column, respectively. Thrombin and Reptilase (Abbott Scientific Products Div., Abbott Laboratories, South Pasadena, Calif.) times of purified patient fibrinogens were prolonged, and calcium ions improved but did not completely correct these defects. Increasing amounts of thrombin progressively shortened the clotting times of patient fibrinogens but not to the level of normal. Addition of equal amounts of patient fibrinogen to normal fibrinogen resulted in a prolongation of the thrombin time of the normal protein. Thrombin-induced fibrinopeptide release was normal. Fibrin monomers prepared from patient plasmas and purified fibrinogens demonstrated impaired aggregation at low (0.12) and high (0.24) ionic strength. These studies demonstrate that some patients with liver disease and prolonged plasma thrombin times have a dysfibrinogenemia functionally characterized by an abnormality of fibrin monomer polymerization.

Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease.

“…Abnormal fibrin monomer polymerization is the most common functional defect reported both in the congenital dysfibrinogenemias (10) and in the acquired dysfibrinogenemias associated with liver disease (1,2) and with hepatoma (11,12). However, in neither the acquired nor the congenital dysfibrinogenemias characterized exclusively by an abnormality of fibrin monomer polymerization has the biochemical basis for this defect been defined.…”

“…All diagnoses were based on clinical and histological criteria. The functional characterization of the abnormal fibrinogen of five of these patients formed the basis of a recent report (1).…”

“…Sodium dodecyl sulfate (SDS)1-polyacrylamide gel electrophoresis of the purified fibrinogen and asialofibrinogen reduced with f8-mercaptoethanol was performed using 7.5% 1 Abbreviations used in this paper: PAS, periodic acidSchiff; SDS, sodium dodecyl sulfate.…”

“…A dysfibrinogenemia functionally characterized by an abnormality of fibrin monomer polymerization has been described in some patients with liver disease (1,2). Because of a suggestion that the carbohydrate composition of fibrinogen may be altered in liver disease (3), and because of previous work in which we This work was presented at the 6th International Congress on Thrombosis and Hemostasis, Philadelphia, Pa., 30 June…”

Type IIB von Willebrand factor with normal sialic acid content induces platelet aggregation in the absence of ristocetin. Role of platelet activation, fibrinogen, and two distinct membrane receptors.

“…Fibrinogen was purified and characterized as reported (21). It was stored in 0.02 M Tris* HCI, 0.15 M NaCl, pH 7.3, at -70'C.…”