Metabolism and Distribution of Fibrinogen. I. FIBRINOGEN TURNOVER IN PHYSIOLOGICAL CONDITIONS IN HUMANS

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Abstract
Summary: The metabolism of human fibrinogen, labelled with radioactive iodine, was studied in 35 healthy subjects over a 5 yr period using eight fibrinogen preparations in 23 labelling procedures. The labelled fibrinogen was highly clottable and homogeneous on agarose gel filtration, immunoelectrophoresis and auto‐radiography. Results in the control subjects were: plasma volume 42 ± 7 ml/kg; plasma fibrinogen concentration 284 ± 71 mg/100 ml; total plasma fibrinogen pool 119 ± 40 mg/kg, representing 0.72 ± 0.07 of the total body pool; fibrinogen half‐life 4.14 ± 0.56 days; fractional catabolic rate 0.24 ± 0.04 of the plasma pool/day; fractional transcapillary efflux rate 0.60 ± 0.26 of the plasma pool/day. Comparable results were obtained for all labelled fibrinogen batches. Anticoagulation with heparin in five control subjects had no influence on the fibrinogen half‐life. Inhibition of the fibrinolytic system with tranexamic acid in five control subjects had no influence on the fibrinogen half‐life in four of them but resulted in a prolongation in one subject.A mathematical compartmental model for the metabolism of fibrinogen is proposed, consisting of one extra vascular compartment and three catabolic pathways (basic protein turnover, intravascular fibrin formation, and intravascular fibrino(geno)lysis). In physiological conditions intravascular fibrin formation or fibrino(geno)lysis are not essential in the fibrinogen turnover.