Elevated plasma levels of P-selectin glycoprotein ligand-1-positive microvesicles in patients with unprovoked venous thromboembolism

Background: Microvesicles (MVs) express antigens from their parental cells and have a highly procoagulant surface. Animal studies suggest that P-selectin glycoprotein ligand-1-positive (PSGL-1(+)) MVs play a role in the pathogenesis of venous thromboembolism (VTE). Objective: The aim of this study was to determine plasma levels, the cellular origin and the morphological characteristics of PSGL-1(+) MVs in patients with unprovoked VTE. Methods: We conducted a population-based case-control study in 20 patients with a history of unprovoked VTE and 20 age- and sex-matched healthy controls recruited from the general population. Plasma levels, the cellular origin and the morphological characteristics of PSGL-1(+) MVs were evaluated using flow cytometry, electron microscopy and confocal microscopy. Results: Plasma levels of PSGL-1(+) MVs were associated with increased risk of VTE. The odds ratio per one standard deviation increase in PSGL-1(+) MVs was 3.11 (95% confidence interval [CI], 1.41-6.88) after adjustment for age and sex, and 2.88 (95% CI, 1.29-6.41) after further adjustment for body mass index. The PSGL-1(+) MVs originated mainly from monocytes and endothelial cells determined by double staining with markers of parental cells using flow cytometry and transmission electron microscopy. Scanning electron microscopy of PSGL-1-labeled plasma-derived MVs displayed dominantly spherical vesicles that varied between 50 and 300 nm in diameter. Conclusions: Increased plasma levels of PSGL-1(+) MVs are associated with the risk of unprovoked VTE. Large population-based prospective studies are required to validate our findings.