title: Altered fibrin architecture is associated with hypofibrinolysis and premature coronary atherothrombosis.
abstract: OBJECTIVE
  Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting.
  
  
  RESULTS
  Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post-myocardial infarction patients with angiographic-proven CAD and in 33 healthy volunteers matched for age and sex. Ex vivo plasma fibrin physical properties were assessed by measuring fibrin rigidity and fibrin morphological properties using a torsion pendulum and optical confocal microscopy. The fibrinolysis rate was derived from continuous monitoring of the viscoelastic properties after addition of lytic enzymes. Young CAD patients had a significant increase in plasma concentration of fibrinogen, von Willebrand factor, plasminogen activator inhibitor type 1, and lipoprotein(a) as compared with controls (P<0.05). Fibrin of young CAD patients was stiffer (P=0.002), made of numerous (P=0.002) and shorter fibers (P=0.04), and lysed at a slower rate than that of controls (P=0.03). Fibrin stiffness was an independent predictor for both premature CAD and hypofibrinolysis.
  
  
  CONCLUSIONS
  This first detailed study of clot properties in such a group of patients demonstrated that abnormal plasma fibrin architecture is an important feature of both premature CAD and fibrinolysis rate. The determinants of this particular phenotype warrant further investigation.
authors.affiliation: Department of Cardiology, Pitié-Salpêtrière University Hospital, Paris, France. jean-philippe.collet@psl.aphp.fr
authors.forename: J P
authors.initials: JP
authors.lastname: Collet
authors.forename: Y
authors.initials: Y
authors.lastname: Allali
authors.forename: C
authors.initials: C
authors.lastname: Lesty
authors.forename: M L
authors.initials: ML
authors.lastname: Tanguy
authors.forename: J
authors.initials: J
authors.lastname: Silvain
authors.forename: A
authors.initials: A
authors.lastname: Ankri
authors.forename: B
authors.initials: B
authors.lastname: Blanchet
authors.forename: R
authors.initials: R
authors.lastname: Dumaine
authors.forename: J
authors.initials: J
authors.lastname: Gianetti
authors.forename: L
authors.initials: L
authors.lastname: Payot
authors.forename: J W
authors.initials: JW
authors.lastname: Weisel
authors.forename: G
authors.initials: G
authors.lastname: Montalescot
mesh_terms: D000328:Adult; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D003328:Coronary Thrombosis / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D004548:Elasticity; D005260:Female; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D018613:Microscopy, Confocal; D009203:Myocardial Infarction / Q000209:etiology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011237:Predictive Value of Tests; D014783:Viscosity; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D017270:Lipoprotein(a); D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D005337:Fibrin; D005340:Fibrinogen