title: Reduced plasma fibrin clot permeability and susceptibility to lysis are associated with increased risk of postthrombotic syndrome.
abstract: BACKGROUND
  The postthrombotic syndrome (PTS) is a severe complication of deep vein thrombosis (DVT). Reduced plasma clot permeability and lysability have been linked to DVT and residual vein obstruction. OBJECTIVES We investigated whether altered fibrin clot properties are associated with the occurrence of PTS.
  
  
  METHODS
  Plasma fibrin clot permeability (Ks ) and lysability were investigated in a cohort of 197 consecutive patients aged 18 to 65 years recruited 3 months following the first-ever DVT. Patients with severe thrombophilia or comorbidities known to adversely affect clot phenotype were ineligible.
  
  
  RESULTS
  During a 1-year follow-up PTS developed in 48 (24%) patients, who were characterized by lower Ks , prolonged fibrin clot lysis time (CLT) and slower release of D-dimer from clots (D-Drate ), together with higher plasma D-dimer, C-reactive protein and thrombin-activatable fibrinolysis inhibitor (TAFI). No PTS-associated differences in fibrinogen, thrombin generation, factor VIII, other fibrinolysis proteins and the quality of anticoagulation were observed. Ks (r = -0.71), CLT (r = 0.45), D-Drate (r = -0.30) and TAFI activity (r = 0.38) were associated with the Villalta scale (all P < 0.05). Recurrent VTE occurred also more commonly in PTS patients during follow-up and the 26 (13.2%) patients had lower Ks , longer CLT and lower D-Drate (all P < 0.05). A multivariate model adjusted for age, body mass index, fibrinogen and glucose showed that independent predictors of PTS were idiopathic DVT, plasma D-dimer, Ks , D-Drate , tissue plasminogen activator and TAFI activity.
  
  
  CONCLUSIONS
  This study demonstrates that formation of more compact fibrin clots displaying impaired susceptibility to lysis predisposes to PTS.
authors.affiliation: Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Siudut
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Grela
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.|Innovative Laboratory Diagnostic Center, John Paul II Hospital, Krakow, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Wypasek
authors.affiliation: Data Analysis Center, Krakow Cardiovascular Research Institute, Krakow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Plens
authors.affiliation: Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland.|Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Undas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D015331:Cohort Studies; D005260:Female; D005337:Fibrin / Q000737:chemistry*; D063285:Fibrin Clot Lysis Time; D005342:Fibrinolysis; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010539:Permeability; D054070:Postthrombotic Syndrome / Q000097:blood* / Q000276:immunology; D012306:Risk; D013917:Thrombin / Q000737:chemistry; D014680:Veins / Q000503:physiopathology; D020246:Venous Thrombosis / Q000097:blood* / Q000276:immunology; D055815:Young Adult
chemical_list: D005337:Fibrin; D013917:Thrombin
keywords: fibrin; fibrinogen; fibrinolysis; postthrombotic syndrome; thrombosis