Reduced plasma fibrin clot permeability and susceptibility to fibrinolysis are associated with increased intima-media thickness in patients with primary antiphospholipid syndrome

Abstract

IntroductionFormation of denser fibrin networks displaying impaired lysability has been reported in subjects at an increased risk of atherosclerosis. Given recent data on prothrombotic fibrin clot phenotype reported in patients with antiphospholipid syndrome (APS), we tested the hypothesis that altered fibrin clot properties are associated with increased intima-media thickness (IMT) observed in PAPS. Materials and methodsWe studied 30 consecutive patients with PAPS and 30 controls matched for age, sex and the type of previous thromboembolism. We assessed plasma fibrin clot permeability (Ks) and clot lysis time (CLT) with their potential determinants. The IMT was measured in 3 segments of the carotid arteries. ResultsPatients with APS had 15.2% lower Ks (p=0.002) and 9.7% prolonged CLT (p=0.039) compared with controls. The IMT in the APS group was greater in the common carotid artery (5.7%; p=0.002), at the bifurcation (17.46%; p<0.001), and the internal artery (9.26%; p=0.015). Patients with triple positivity in the antiphospholipid antibody profile (n=9; 30%) had lower Ks and greater IMT (both, p<0.05), compared with those with single positivity (n=13; 43.3%). Multivariate analysis adjusted for potential confounders showed that in APS patients, oxidized low-density lipoproteins (p=0.019) were the only independent predictor of Ks, while thrombin activatable fibrinolysis inhibitor activity (p<0.001) predicted CLT. Plasminogen activator inhibitor-1 (PAI-1) was found to be the independent predictor of the IMT in the common carotid artery (p=0.004), and in the internal carotid artery (p<0.001). ConclusionsReduced Ks and susceptibility to lysis are associated with greater IMT in PAPS, which might contribute to the early atherosclerosis in this disease.