Catabolism of Fibrinogen and its Derivatives

Summary

Although 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.

• References

• 1 Ardaillou N, Dray L, Budzynski A. Z, Marder V. J, Larrieu M. J. 1977; The half-life of plasmin degradation products of human fibrinogen in rabbits. Thrombosis and Haemostasis 37: 201.
• 2 Ashwell G, Morell A. G. 1974; The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Advances in Enzymology 41: 99.
• 3 Astrup T. 1956; The biological significance of fibrinolysis. Lancet II: 565.
• 4 Bang N. U, Hansen M. S, Smith G. F, Mosesson M. W. 1973. Properties of soluble fibrin polymers encountered in thrombotic states. In: Present status of Thrombosis. (ed.) Losito R. New York: 1973. F. K. Schattauer Verlag; 75.
• 5 Bone J. M, Sherman L. A, Valdes A. J, Lubowitz H. 1977; On the origin of urinary fibrin-fibrinogen-related antigen in glomerulonephritis. Journal of Laboratory and Clinical Medicine 89: 1043.
• 6 Catanzaro A, Edgington T. S. 1974; The in vivo behavior of the terminal derivatives of fibrinogen and fibrin cleared by plasmin. Journal of Laboratory and Clinical Medicine 83: 458.
• 7 Chang M. L, Boxer L. A. 1976; Cellular clearance of fibrinogen-fibrin degradation products. Federation Proceedings 35: 648 Abstract.
• 8 Chang M. L, Bang N. U, Truex L, Boxer L, Mattler L. E, Marks L. A. 1977; Degradation of soluble fibrin complexes, fibrinogen, and fibrin by macrophage enzymes. Thrombosis and Haemostasis 38: 102 Abstract.
• 9 Fletcher A. P, Alkjaersig H, O’Brien J, Tulevski V. G. 1970; Blood hypercoagulability and thrombosis. Transactions of the Association of American Physicians 83: 159.
• 10 Fletcher A. P, Alkjaersig N, Sherry S. 1961; Pathogenesis of the coagulation defect developing during pathological plasma proteolytic (fibrinolytic) states. I. The significance of fibrinogen proteolysis and circulating fibrinogen breakdown products. Journal of Clinical Investigation 41: 896.
• 11 Harker L. A, Slichter S. J. 1974; Arterial and venous thrombosis: kinetic characterization and evaluation of therapy. Thrombosis et Diathesis Haemorrhagica 31: 188.
• 12 Hayne O. A, Sherman L. A. 1973; In Vivo behavior of fibrinogen fragment D in experimental renal, hepatic and reticuloendothelial dysfunction. American Journal of Pathology 2: 219.
• 13 Hemker H. C, Fekkes N, Hensen A, Schrijvr H, Loeliger E. A. 1966; Quantitation of circulating fibrinogen breakdown products in intravascular clotting. Thrombosis et Diathesis Haemorrhagica Suppl. 20: 227.
• 14 Horn R. G. 1973; Evidence for participation of granulocytes in the pathogenesis of the generalized Shwartzman reaction: a review. Journal of Infectious Diseases 128 Suppl. 134.
• 15 Iio A, Rutherford W. E, Wochner R. D, Spilberg L, Sherman L. A. 1976; The roles of renal catabolism and uremia in modifying the clearance of fibrinogen and its degradative fragments D and E. Journal of Laboratory and Clinical Medicine 87: 934.
• 16 Kierulf P. 1973; Studies on soluble fibrin in plasma. II. N-terminal analysis of a modified fraction I (Cohn) from patient plasmas. Scandinavian Journal of Clinical Laboratory Investigation 31: 37.
• 17 Korst D. R, Kratochril C. H. 1955; »Cryofibrinogen« in case of lung neoplasma associated with thrombophlebitis migran. Blood 10: 945.
• 18 Kowalski E. 1968; Fibrinogen derivatives and their biologic activities. Seminars in Hematology 5: 45.
• 19 Lewis J. H, Szeto I. L, Bayer W. L, Curiel D. C. 1972; Leukofibrinolysis. Blood 40: 844.
• 20 Lipinska L, Lipinski B, Gurewich V. 1974; Fibrinogen heterogeneity in human plasma. Electrophoretic demonstration and characterization of two major fibrinogen components. Journal of Laboratory and Clinical Medicine 84: 5.
• 21 Lipinska L, Lipinski B, Gurewich V, Hiffmann K. D. 1976; Fibrinogen heterogeneity in cancer, in occlusive vascular disease, and after surgical procedures. American Journal of Clinical Pathology 66: 958.
• 22 Lipinski B, Lipinska I, Gurewich V. 1974; The fibrinogenolytic pathway of fibrinogen catabolism: Additional comments. Thrombosis Research 4: 891.
• 23 Lipinski B, Nowak A, Gurewich V. 1974; The organ distribution of ¹²⁵I-fibrin in the generalized Shwartzman reaction and its relation to leucocytes. British Journal of Haematology 28: 221.
• 24 Lipinski B, Worowski K. 1968; Detection of soluble fibrin monomer complexes in blood by means of protamine sulfate test. Thrombosis et Diathesis Haemorrhagica 20: 44.
• 25 Martinez J, Palascak J, Paters C. 1977; Functional and metabolic properties of human asialofibrinogen. Journal of Laboratory and Clinical Medicine 89: 367.
• 26 Mcfarlane A. S. 1958; Efficient trace-labeling of proteins with iodine. Nature 182: 53.
• 27 Mcfarlane A. S. 1963; In vivo behavior of I¹³¹-fibrinogen. Journal of Clinical Investigation 42: 346.
• 28 McKee P. A, Kalbfleisch J. M, Bird R. M. 1963; Incidence and significance of cryofibrinogenemia. Journal of Laboratory and Clinical Medicine 61: 203.
• 29 Merskey C. 1973; Editorial: Defibrination syndrome or …?. Blood 41: 599.
• 30 Moroz L. A, Gilmore N. J. 1976; Fibrinolysis in normal plasma and blood: Evidence for significant mechanisms independent of the plasminogen-plasmin system. Blood 48: 531.
• 31 Mosesson M. W, Colman R. W, Sherry S. 1968; Chronic intravascular coagulation syndrom: report of a case with special studies of an associated plasma cryoprecipitate (»cryofibrinogen«). New England Journal of Medicine 278: 815.
• 32 Mosesson M. W, Sherry S. 1966; The preparation and properties of human fibrinogen of relatively high solubility. Biochemistry 5: 2829.
• 33 Mosesson M. W, Umfleet R. A. 1970; The cold-insoluble globulin of human plasma. I. Purification, primary characterization, and human relationship to fibrinogen and other cold-insoluble fraction components. Journal of Biological Chemistry 245: 5728.
• 34 Mosesson M. W, Finlayson J. S. 1974; The fibrinogenolytic pathway of fibrinogen catabolism: A rebuttal. Thrombosis Research 4: 895.
• 35 Muller-Berghaus G, Eckhardt T, Kramer W. 1976; The role of leukocytes and platelets in the precipitation of fibrin in vivo: Mechanisms of the generation of microclots from soluble fibrin. Thrombosis Research 8: 725.
• 36 Muller-Berghaus G, Mahn I, Koveker G, Maul F.-D. 1976; In vivo behavior of homologous urea-soluble ¹³¹I-fibrin and ¹²⁵I-fibrinogen in rabbits: the effect of fibrinolysis inhibition. British Journal of Haematology 33: 61.
• 37 Nilsson I. M, Hedner U. 1971. FDP and renal disease. In: Immunological Mechanisms in Blood, Coagulation, Thrombosis, and Hemostasis. (eds.) Duckert F, Brinkhous K. M. New York: Schattauer Verlag; 203.
• 38 Nossel H. L, Butler Jr. V. P, Canfield R. E, Yudelman I, Ti M, Spanodis K, Soland T. 1975; Potential use of fibrinopeptide: A measurement in the diagnosis and management of thrombosis. Thrombosis et Diathesis Haemorrhagica 33: 426.
• 39 Nossel H. L, Yudelman I, Canfield R. E, Butler Jr. V. P, Spanodis K, Wilner G. D, Qureshi G. D. 1974; Measurement of fibrinopeptide A in human blood. Journal of Clinical Investigation 54: 43.
• 40 Plow E. F, Edgington T. S. 1975; An alternative pathway for fibrinolysis. I. The cleavage of fibrinogen by leukocyte proteases at physiologic pH. Journal of Clinical Investigation 56: 30.
• 41 Poortmans J, Luke K. H, Zipursky A, Bienenstock J. 1971; Fibrinolytic activity and fibrinogen split products in exercise proteinuria. Clinica Chimica Acta 35: 449.
• 42 Regoeczi E. 1970. Abnormal fibrinogen metabolism. In: Rothschild M. A, Waldmann T. (eds.) Plasma protein metabolism. Academic Press; New York: 459.
• 43 Sasaki T, Page I. H, Shainoff J. R. 1966; Stable complex of fibrinogen and fibrin. Science 152: 1069.
• 44 Shainoff J. R, Page I. H. 1960; Cofibrins and fibrin-intermediates as indicators of thrombin activity in vivo. Circulation Research 8: 1013.
• 45 Shainoff J. R, Page I. H. 1962; Significance of cryoprofibrin in fibrinogen-fibrin conversion. Journal of Experimental Medicine 116: 687.
• 46 Sherman L. A. 1972; Fibrinogen turnover: Demonstration of multiple pathways of catabolism. Journal of Laboratory and Clinical Medicine 79: 710.
• 47 Sherman L. A, Fletcher A. P, Sherry S. 1969; In vivo transformation between fibrinogen of varying ethanol solubilities: a pathway of fibrinogen catabolism. Journal of Laboratory and Clinical Medicine 73: 574.
• 48 Sherman L. A. 1974; Reply to the fibrinogenolytic pathway of fibrinogen catabolism. A comment. Thrombosis Research 4: 901.
• 49 Sherman L. A, Harwig S, Lee J. 1975; In vitro formation and in vivo clearance of fibrinogen: fibrin complexes. Journal of Laboratory and Clinical Medicine 86: 100.
• 50 Sherman L. A, Lee J. 1977; Specific binding of soluble fibrin to macrophages. Journal of Experimental Medicine 145: 76.
• 51 Sherman L. A, Lee J, Jacobson A. 1977 Quantitation of the reticuloendothelial system clearance of soluble fibrin. British Journal of Haematology. in press.
• 52 Sherman L. A, Lee J, Stewart C. C. 1977; Release of fibrinolytic enzymes by macrophages in response to soluble fibrin. Thrombosis and Haemostasis 38: 46 Abstract.
• 53 Smith R. T, von Korff R. W. 1957; Heparin-precipitable fraction of human plasma. I. Isolation and characterization of fraction. Journal of Clinical Investigation 36: 596.
• 54 Takeda Y. 1966; Studies on the metabolism and distribution of fibrinogen in healthy men with autologous ¹²⁵I-labeled fibrinogen. Journal of Clinical Investigation 45: 103.
• 55 Tytgat G. N, Collen D, Vermylen J. 1972; Metabolism and distribution of fibrinogen. II. Fibrinogen turnover in polycythemia, thrombocytosis, haemophilia A, congenital afibrinogenemia, and during streptokinase therapy. British Journal of Haematology 22: 701.
• 56 Unkeless J. C, Gordon S, Reich E. 1974; Secretion of plasminogen activator by stimulated macrophages. Journal of Experimental Medicine 139: 834.
• 57 von Hugo R, Hafer R, Stein B, Stemberger A, Rjosk H, Graeff H. 1977; Incorporation of ¹²⁵I-fibrinogen in circulating soluble fibrin monomer complexes during hypercoagulability. Thrombosis Research 10: 703.
• 58 Wegrzynowicz Z, Kopec M, Latallo Z. S. 1971; Formation of soluble fibrin complexes and some factors affecting their solubility. Scandinavian Journal of Haematology Suppl. 13: 49.