title: Fibrin resistance to lysis in patients with pulmonary hypertension other than thromboembolic.
abstract: BACKGROUND
  Reportedly, fibrin isolated from patients with chronic thromboembolic pulmonary hypertension (CTEPH) is resistant to lysis. Persistence of regions within the fibrin beta chain, which mediate cell signaling and migration, could trigger the organization of pulmonary thromboemboli into chronic intravascular scars.
  
  
  OBJECTIVE
  Ascertain whether fibrin resistance to lysis occurs in patients with pulmonary hypertension (PAH) other than CTEPH, and in those with prior pulmonary embolism (PE) and no pulmonary hypertension.
  
  
  METHODS
  Fibrinogen was purified from 96 subjects (17 with CTEPH, 14 with PAH, 39 with prior PE, and 26 healthy control subjects) and exposed to thrombin to obtain fibrin clots. Plasmin-mediated cleavage of fibrin beta chain was assessed hourly over a 6-hour period by polyacrylamide gel electrophoresis. Fibrin band intensity was measured by densitometry of stained gels. Data were normalized to the band intensity of the undigested protein.
  
  
  RESULTS
  By 1 hour of digestion, fibrin band intensity had decreased by a median of 25% (interquartile range [IQR], 20 to 27%) in control subjects, and by 15% (IQR, 11 to 18%) in patients with prior PE (P < 0.0001). The 1-hour median reduction in band intensity was 2% (IQR, 1 to 3%) in CTEPH, and 4% (IQR, 2 to 7%) in PAH (P < 0.0001 vs. control subjects and PE). The decline in fibrin band intensity remained significantly different among the four groups up to 6 hours (P < 0.0001).
  
  
  CONCLUSIONS
  Fibrin resistance to lysis occurs in pulmonary hypertension other than CTEPH and, to a smaller extent, in patients with prior PE and no pulmonary hypertension.
authors.affiliation: Dipartimento di Area Critica Medico Chirugica, Università di Firenze, Viale Morgagni 85, 50134 Florence, Italy. massimo.miniati@unifi.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Miniati
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorillo
authors.forename: Matteo
authors.initials: M
authors.lastname: Becatti
authors.forename: Simonetta
authors.initials: S
authors.lastname: Monti
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.forename: Carlo
authors.initials: C
authors.lastname: Marini
authors.forename: Elisa
authors.initials: E
authors.lastname: Grifoni
authors.forename: Bruno
authors.initials: B
authors.lastname: Formichi
authors.forename: Carolina
authors.initials: C
authors.lastname: Bauleo
authors.forename: Chiara
authors.initials: C
authors.lastname: Arcangeli
authors.forename: Daniela
authors.initials: D
authors.lastname: Poli
authors.forename: Paolo Antonio
authors.initials: PA
authors.lastname: Nassi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Domenico
authors.initials: D
authors.lastname: Prisco
mesh_terms: D000328:Adult; D001797:Blood Protein Electrophoresis; D004452:Echocardiography; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005337:Fibrin / Q000502:physiology*; D005342:Fibrinolysis; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000097:blood
chemical_list: D005337:Fibrin