Altered fibrin architecture is associated with hypofibrinolysis and premature coronary atherothrombosis

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.