Stimulation of fibrinogen synthesis: a possible functional role of fibrinogen degradation products.

Fibrinogen production. measured by the rate of incorporation of 75Se-selenomethionine into newly synthesized circulating fibrinogen. was determined in rabbits administered urokinase and ancrod to generate degradation products of fibrinogen or fibrin in vivo. Fibrinogen degradation products appeared in elevated titers in metabolically normal animals after receiving infusions of urokinase. Fibrinogen production was increased fourfold to fivefold. while the basal synthesis of nonclottable proteins was unaffected. In rabbits rendered afibrinogenemic by intravenous ancrod. 2 U/kg. fibrinogen production was not accelerated unless 1 50 mg of homologous fibrinogen were infused slowly into the afibrinogenemic animals at the time of peak generation of degradation products. This technique produced a threefold increase in fibrinogen synthesis. When partial defibrinogenation was accomplished with ancrod. 0.75 U/kg over 1 hr. elevated titers of degradation products were detected and. subsequently. f.brinogen synthesis was enhanced twofold. These data suggest that ancrod at 2 U/kg may convert fibrinogen to fubrin so rapidly that only fibrin degradation products are formed. These probably do not influence fibrinogen synthesis; however. if fibrinogen is available as a substrate for the activated plasminogen-plasmin system. fibrinogen degradation products may be generated and subsequently may mediate the stimulation of fibrinogen synthesis.