title: The effect of blood coagulation factor XIII on fibrin clot structure and fibrinolysis.
abstract: BACKGROUND
  Factor XIII is a 320 kDa tetramer, comprising two enzymatic A-subunits and two carrier B-subunits (FXIII A₂ B₂). Activated FXIII (FXIIIa) catalyses the formation of ε-(γ-glutamyl)lysyl covalent bonds between γ-γ, γ-α and α-α chains of adjacent fibrin molecules and also cross-links the major plasmin inhibitor, α2-antiplasmin, to fibrin.
  
  
  OBJECTIVE
  We investigated the role of FXIII cross-linking of fibrin directly in clot morphology and its functional effect on clot formation and lysis, in the absence of α2-antiplasmin.
  
  
  CONCLUSIONS
  Our data show that the presence of FXIII during clot formation results in fibrin clots that have a significant 2.1-fold reduction in pore size, as determined by the Darcy constant, Ks, and formed thinner fibers (74.7 ± 1.5 nm) and higher density of fibers compared with those without FXIII (86.0 ± 1.7 nm, P < 0.001), as determined by scanning electron microscopy. Additionally, fibrinolysis showed a significant increase in the time to lysis for clots formed in the presence of FXIII in both static and flow systems. These data demonstrate that independent of α2-antiplasmin, FXIII activity plays a role in increasing the stability of the fibrin clot by altering its structure and increasing the resistance to fibrinolysis.
authors.affiliation: Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, Faculty of Medicine and Health, Leeds Institute for Genetics Health and Therapeutics, University of Leeds, Leeds, UK.
authors.forename: E L
authors.initials: EL
authors.lastname: Hethershaw
authors.forename: A L
authors.initials: AL
authors.lastname: Cilia La Corte
authors.forename: C
authors.initials: C
authors.lastname: Duval
authors.forename: M
authors.initials: M
authors.lastname: Ali
authors.forename: P J
authors.initials: PJ
authors.lastname: Grant
authors.forename: R A S
authors.initials: RA
authors.lastname: Ariëns
authors.forename: H
authors.initials: H
authors.lastname: Philippou
mesh_terms: D002850:Chromatography, Gel; D005176:Factor XIII / Q000502:physiology*; D005337:Fibrin / Q000737:chemistry / Q000502:physiology*; D005342:Fibrinolysis; D006801:Humans; D018613:Microscopy, Confocal
chemical_list: D005337:Fibrin; D005176:Factor XIII
keywords: blood coagulation; electron microscopy; factor XIII; fibrin; fibrinolysis