title: Increased resistance to plasmic degradation of fibrin with highly crosslinked alpha-polymer chains formed at high factor XIII concentrations.
abstract: We have previously demonstrated that increasing factor XIII concentrations above that present in plasma (1 U/mL) results in the formation of very high molecular weight alpha fate polyacrylamide and agarose gel electrophoresis (SDS-PAGE). In this report, we have examined the effect of such crosslinking on plasmic susceptibility of fibrin prepared from purified fibrinogen and from plasma in the presence of factor XIII concentrations between 0 and 10 U/mL. The crosslinking achieved with purified fibrinogen at 1 U/mL factor XIII increased resistance to plasmic degradation by 32% as measured in a radiolabeled clot lysis system. However, further increases in plasmic resistance occurred at factor XIII concentrations of 2 and 10 U/mL, the latter decreasing the lysis rate to 45% of that which occurred in the absence of factor XIII. To achieve the same rate of clot lysis with fibrin formed using 10 U/mL rather than 1 U/mL of factor XIII, an increase in plasmin concentration of up to 4.2-fold was required. Similar results were obtained using clots prepared from plasma in the presence of factor XIII concentrations greater than 1 U/mL. Since the alpha 2-plasmin inhibitor content was the same for fibrin at 1 or 10 U/mL factor XIII, the increasing plasmic resistance could not be attributed to increased binding of the inhibitor. We conclude that fibrin prepared in the presence of factor XIII at concentrations exceeding that in plasma shows increased resistance to plasmic degradation, which is likely explained by the formation of very high molecular weight alpha polymer chains.
authors.affiliation: Department of Medicine, University of Rochester School of Medicine and Dentistry, NY 14642.
authors.forename: C W
authors.initials: CW
authors.lastname: Francis
authors.forename: V J
authors.initials: VJ
authors.lastname: Marder
mesh_terms: D003432:Cross-Linking Reagents / Q000494:pharmacology; D005176:Factor XIII / Q000494:pharmacology*; D005337:Fibrin / Q000096:biosynthesis; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D000979:alpha-2-Antiplasmin / Q000494:pharmacology
chemical_list: D003432:Cross-Linking Reagents; D000979:alpha-2-Antiplasmin; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; D005341:Fibrinolysin