title: Up-regulation of the extrinsic coagulation pathway in acute asthma--a case study.
abstract: BACKGROUND
  In the normal airway, the hemostatic balance is antithrombotic and favors fibrinolysis. Acute asthma is associated with inflammatory cell infiltrate and plasma exudation in the airways. Postmortem specimens following status asthmaticus suggest a role for the activation of the extrinsic coagulation cascade and intraluminal fibrin formation. The authors report a chance observation of fibrin formation in the airways of a patient with moderate asthma 5 days before a severe exacerbation requiring hospital admission.
  
  
  METHODS
  Alpha-2 macroglobulin, an index of plasma leakage, coagulation factors, and D-dimers were measured by enzyme-linked immunosorbent assay (ELISA) in hypertonic saline-induced sputum, as part of a study into airway repair in stable asthma. All subjects were required to have stable symptoms and measures of asthma prior to sampling.
  
  
  RESULTS
  The subject's baseline forced expiratory volume in one second (FEV(1)) was 94% predicted and fraction of exhaled nitric oxide (FeNO) level was 30 ppb prior to sputum induction. Differential sputum cell count revealed an airways neutrophilia (neutrophils 81.1%, eosinophils 0.19%). D-dimers were 70-fold and 22-fold higher than the median value for patients with stable moderate and severe asthma, respectively. Plasma exudation was 42-fold higher than in stable moderate asthma, but on a par with levels found in severe stable asthma, and locally produced coagulation factors may therefore be involved. Levels of fibrinogen, plasminogen, plasminogen activator inhibitor (PAI)-1 and thrombin-activatable fibrinolysis inhibitor (TAFI) were all at least an order of magnitude higher than those seen in stable moderate or severe asthma.
  
  
  CONCLUSIONS
  Acute exacerbation of moderate asthma appears to be associated with a shift to a profibrinogenic, possibly antifibrinolytic, environment in the airways.
authors.affiliation: Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK. fraserbrims@googlemail.com
authors.forename: Fraser J H
authors.initials: FJ
authors.lastname: Brims
authors.forename: Anoop J
authors.initials: AJ
authors.lastname: Chauhan
authors.forename: Bernie
authors.initials: B
authors.lastname: Higgins
authors.forename: Janis K
authors.initials: JK
authors.lastname: Shute
mesh_terms: D000368:Aged; D001249:Asthma / Q000097:blood* / Q000276:immunology; D001777:Blood Coagulation / Q000276:immunology*; D025901:Carboxypeptidase B2 / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005337:Fibrin / Q000276:immunology; D005338:Fibrin Fibrinogen Degradation Products / Q000276:immunology; D005340:Fibrinogen / Q000276:immunology; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010958:Plasminogen / Q000276:immunology; D017395:Plasminogen Activator Inhibitor 1 / Q000276:immunology; D013183:Sputum / Q000276:immunology; D015854:Up-Regulation
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C036309:fibrin fragment D; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D025901:Carboxypeptidase B2