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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2567.)
© 2006 American Heart Association, Inc.

Thrombosis

Altered Fibrin Architecture Is Associated With Hypofibrinolysis and Premature Coronary Atherothrombosis

J.P. Collet; Y. Allali; C. Lesty; M.L. Tanguy; J. Silvain; A. Ankri; B. Blanchet; R. Dumaine; J. Gianetti; L. Payot; J.W. Weisel; G. Montalescot

From the Departments of Cardiology (J.-P.C., Y.A., J.S., B.B., R.D., J.G., L.P., G.M.), Haematology (C.L., A.A.), and Biostatistics (M.L.T.), Pitié-Salpêtrière University Hospital, Paris, France; and Department of Cell & Developmental Biology (J.-P.C., J.W.W.), University of Pennsylvania School of Medicine, Philadelphia.

Correspondence to J.-P. Collet, MD, PhD, Department of Cardiology, Centre Hospitalier Universitaire Pitié-Salpêtrière, 47, boulevard de l’Hôpital, 75013 Paris, France. E-mail jean-philippe.collet{at}psl.aphp.fr

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.

Methods and 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.

Hypofibrinolysis promotes atherosclerosis and recurrent ischemic events in premature coronary artery disease (CAD). In the present investigation, plasma fibrin of young CAD patients was found to be significantly stiffer and more resistant to lysis as compared with matched controls. In addition, plasma fibrin stiffness was an independent correlate for both premature CAD and hypofibrinolysis, suggesting an important pathophysiological role of altered fibrin properties.

Key Words: acute coronary syndromes • coagulation • fibrinolysis • pathophysiology • fibrinogen • thrombophilia

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