title: Denser plasma clot formation and impaired fibrinolysis in paroxysmal and persistent atrial fibrillation while on sinus rhythm: association with thrombin generation, endothelial injury and platelet activation.
abstract: BACKGROUND
  Formation of compact and poorly lysable fibrin clots have been demonstrated in patients following ischemic stroke. Recently, it has been shown that denser fibrin networks and impaired fibrinolysis occurs in subjects with permanent atrial fibrillation (AF). Fibrin clot phenotype in other types of AF remains to be established. We evaluated fibrin clot properties in paroxysmal (PAF) and persistent AF (PsAF).
  
  
  METHODS
  We studied 88 non-anticoagulated patients with AF on sinus rhythm and free of stroke (41 with PAF, 47 with PsAF) versus 50 controls. Ex-vivo plasma fibrin clot permeability (Ks) and clot lysis time (CLT) were evaluated along with von Willebrand factor (vWF), peak thrombin generation (TG), platelet factor 4 (PF4) and fibrinolytic proteins.
  
  
  RESULTS
  Compared with control subjects, clots obtained from plasma of patients with PAF and PsAF had similarly lower Ks (-7.7%, P=0.01; -8.6%, P=0.005, respectively) and prolonged CLT (+10.8%, P=0.006; +7.8% P=0.04, respectively). No associations of Ks and CLT with CHA2DS2-VASc and HAS-BLED score were observed. Patients with AF had higher TG, vWF, PF4 and plasminogen activator inhibitor-1 (PAI-1) antigen compared with controls. Multiple linear regression adjusted for age, gender, body mass index and fibrinogen showed that TG (β=-0.41), vWF (β=-0.29) and PF4 (β=-0.28) are the independent predictors of Ks (R(2)=0.78), while CLT was independently predicted by TG (β=0.37), PAI-1 antigen (β=0.29) and vWF (β=0.26) in the AF group (R(2)=0.39).
  
  
  CONCLUSIONS
  Patients with PAF and PsAF while on sinus rhythm display unfavorably altered fibrin clot properties, which might contribute to thromboembolic complications.
authors.affiliation: John Paul II Hospital, Krakow, Poland; Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Drabik
authors.affiliation: Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Wołkow
authors.affiliation: John Paul II Hospital, Krakow, Poland; Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. Electronic address: mmundas@cyf-kr.edu.pl.
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
mesh_terms: D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications; D001777:Blood Coagulation; D002908:Chronic Disease; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D013917:Thrombin / Q000378:metabolism; D013923:Thromboembolism / Q000097:blood* / Q000209:etiology; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000209:etiology
chemical_list: D005337:Fibrin; D013917:Thrombin
keywords: Atrial fibrillation; Clot lysis time; Fibrinolysis; Thrombin; Thromboembolism