Catabolism of Fibrinogen and its Derivatives

Abstract

SummaryAlthough the site and manner of normal catabolism of most of the fibrinogen pool is uncertain, certain pathways have been defined for various fibrinogen derivatives. Several organs, including the kidneys and reticuloendothelial system (RES) have been directly implicated as catabolic sites for various fibrinogen derivatives. The catabolic sites are not the same for different derivatives. These differences in catabolism are probably in part related to biochemical differences between fibrinogen and its various derivatives. Fibrinogen itself may be catabolized in endothelial cells, although little experimental data is available. RES uptake of intact fibrinogen does not occur, and removal of sialic acid does not result in the rapid hepatic uptake seen with other desialop rote ins. In contrast, a variety of studies have shown that fibrin is taken up by the RES by at least 2 mechanisms. The first is phagocytosis of microparticulate fibrin. The second involves a RES cell membrane binding of soluble fibrin which remains soluble in the blood, when complexed to fibrinogen or degradation products. Fibrinogen degradation products alone may in part also be cleared in the RES. Fragments D and E appear to be catabolized in the kidney, although both the intrarenal site of catabolism and the means of cellular uptake is unknown. It is clear that normally there is no urinary excretion of D and E. Another fibrinogen derivative, low molecular weight clottable fraction 1–8, is derived in vivo from intact fibrinogen. 1–8 is found normally in the blood and has a shorter t ½ than fibrinogen although much longer than D and E. While originally thought to be the result of limited plasmin degradation, 1–8 may be the result of another type of proteolysis. The sites of both 1–8 formation and degradation are unknown. Catabolism via fibrin, 1–8, or D and E appears to be only a small percent of normal turnover, albeit of much greater significance in disease. The relationship of these pathways to the as yet unknown catabolic site for the bulk of normal fibrinogen remains to be determined.