In Vivo Catabolism of Human Fibrinogen Fragment D in Normal Subjects and Patients with Liver Cirrhosis

The in vivo catabolism of purified 131-I-fragment D (Fg D) was studied in comparison with that of 125-I-Fibrinogen (Fg) simultaneously injected in 6 controls and 8 patients with liver cirrhosis. Fg D, M.W. 85,000, was obtained following prolonged (24 hours) plasmin digestion of human Fg. Labelling was performed using the chloramine T method. Linlabelled and labelled Fg and Fg D were characterized hy immunoelectrophoresis and SDS Polyacrylamide gel electrophoresis. Radioactivity was measured in thrombin-clottable (Fg) and TCA-precipitable (Fg D) proteins from plasma. Labelled Fg D present in plasma samples 1, 6 and 12 hours following injection eluted from Sephadex G 2D0 at the same position as native Fg D. A two compartment system was derived from the corresponding plasma disappearance curves for both Fg and Fg D in controls and patients. In controls, the first component of Fg D disappearance curve represented 54.1±13.4% of the total clearance with T 1/2 of 2.5±0.9 hours. The T 1/2 of the second component was 3.9±1.0 hours, Fg D disappeared more rapidly from plasma than Fg, and the ratio of Fg D to Fg was 0.11-0,02. In patients with liver cirrhosis, there was a significant (p<0.005) increase of T 1/2 of the second component (13.6±2.6 hours), whereas the in vivo survival of Fg was normal (4 cases) or decreased (2 cases). These results suggest that the liver interfers with the metabolic clearance rate of Fg D.