Metabolism and distribution of fibrinogen. II. Fibrinogen turnover in polycythaemia, thrombocytosis, haemophilia A, congenital afibrinogenaemia and during streptokinase therapy.

Abstract

Summary.The kinetics of fibrinogen metabolism in humans were investigated by turnover studies in various pathological conditions in order to evaluate the proposed flow diagram of labelled fibrinogen. Six patients with primary or secondary polycythaemia had a significantly shortened fibrinogen half‐life of 2.87 ± 0.35 days and a signlficantly increased fractional catabolic rate of 0.33 ± 0.06 of the plasma poollday. This shortened fibrinogen half‐life together with the correcting effect of heparinization on the fibrinogen turnover indicated that fibrinogen was consumed by chronic disseminated intravascular coagulation. The average fibrinogen half‐life of 3.17 ± 0.54 days and the average fractional catabolic rate constant of 0.31 rt: 0.08 in eight patients with thrombocytosis were significantly different from the cor‐ responding control values. A prolongation of the plasma radioactive decay was induced by anticoagulation as well as by fibrinolytic inhibition, demonstrating the close relationship between in vivo coagulation and (secondary?) fibrinolysis. The turnover of fibrinogen in 11 haemophilia A patients was significantly shortened, the half‐life being 3.73 k 0.36 days and the fractional catabolic rate being 0.271 0.05 of the plasma poollday. Autologous and homologous fibrinogen, prepared in different ways, behaved identically in haemophiliacs. The accelerated fibrinogen catabolism could be explained either by consumption in tissue repair mechanisms, by fibrino(geno)lytic breakdown or by immunological phenomena. No influence on the first order fibrinogen catabolism was observed, either during elevation of the plasma fibrinogen concentration by cryoprecipitate transfusion in two haemo‐ philiacs or during decrease in fibrinogen level as seen in two patients with congenital afibrinogenaemia. Activation of the fibrinolytic system by streptokinase in six patients resulted in a markedly accelerated fibrinogen turnover by in vivo fibrino‐ (gen0)lysis. These experiments demonstrate that fibrinogen catabolism by in uiuo coagulation and (or) fibrino(gen0)lysis are distinct pathways in the flow diagram of labelled fibrinogen metabolism.