title: Evidence for age-related differences in human fibrinogen.
abstract: Fibrinogen has previously been demonstrated to exist in a 'fetal' form, in cord blood of term infants, with increased sialic acid content compared to adult fibrinogen. The functional implications of these differences are reflected in prolonged thrombin clotting times in newborns as well as differences in polymerization of fibrin from 'fetal' fibrinogen. Despite numerous studies of fibrinogen structure and function, the age at which 'fetal' fibrinogen reverts to the adult form, as well as the physiological significance of this phenomenon remains unknown. This study was designed to determine whether the difference between the 'fetal' and the 'adult' fibrinogen molecule persists in a 'childhood' form throughout progression from infancy to adulthood. The results demonstrate that although the concentration of fibrinogen from day 1 neonates is decreased compared to adult fibrinogen, functional activity of this protein is comparable in both age groups. In addition, despite there being quantitatively less fibrinogen in day 3 and 11-16-year age groups, this protein is functionally more active compared to adult fibrinogen. In addition, the molecular weight of the Aα fibrinogen chain was consistently higher by up to 1500 Da in neonates and children compared to adults, suggesting age-specific differences in posttranslational modification of this chain of the protein.These age-related differences in fibrinogen could provide a protective mechanism against excessive polymerization and proteolysis of this protein, providing a possible explanation of the thromboprotective mechanism that is functioning in neonates and children.
authors.affiliation: Haematology Research, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia. verai@unimelb.edu.au
authors.forename: Vera
authors.initials: V
authors.lastname: Ignjatovic
authors.forename: Aysel
authors.initials: A
authors.lastname: Ilhan
authors.forename: Paul
authors.initials: P
authors.lastname: Monagle
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000097:blood; D002648:Child; D004591:Electrophoresis, Polyacrylamide Gel; D005337:Fibrin / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry / Q000378:metabolism*; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D013058:Mass Spectrometry; D058105:Polymerization; D012794:Sialic Acids / Q000097:blood; D013918:Thrombin Time
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D012794:Sialic Acids; C464794:fibrinogen Aalpha; D005337:Fibrin; D005340:Fibrinogen