Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1–2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE.

Background: Valvular heart disease remains a major global health issue, with mechanical prosthetic heart valves (MPHVs) widely used in surgical valve replacement. However, these devices carry a risk of thrombosis, particularly in the mitral position. Several mechanisms may be involved in this risk, but the role of oxidative stress (OxS) remains unclear. Our aim was to assess the relationship between OxS impairment and platelet activation. Methods: We analyzed data from a pilot, observational, monocentric study conducted at our anticoagulation clinic at Sapienza University of Rome, involving adult patients with MPHVs (aortic or mitral) on vitamin K antagonist therapy, enrolled between June and September 2024. Clinical data and blood samples were collected to evaluate markers of NOX2-mediated OxS (sNOX2-dp, H₂O₂) and platelet activation (sCD40L) using ELISA-based assays. Results: Our cohort included 30 patients with mitral MPHVs and 30 patients with aortic MPHVs (46.7% males, 53.3% females). Serum sNOX2-dp and H₂O₂ were significantly higher in patients with mitral MPHVs (28.69 [25.08–33.18] vs. 24.27 [17.30–26.41] pg/mL, p = 0.001, and 22.94 [15.79–27.33] vs. 16.73 [12.50–20.87] µM, p = 0.013, respectively) compared with aortic MPHV patients. sCD40L was significantly elevated in mitral versus aortic MPHVs (5.61 [3.69–6.89] vs. 3.65 [2.14–5.54] ng/mL, p = 0.009). Spearman’s correlation analysis showed a significant correlation between sNOX2-dp levels and sCD40L in both groups (mitral MPHVs: r_s = 0.521, p = 0.003; aortic MPHVs: r_s = 0.443, p = 0.014). Conclusions: Mitral MPHVs are associated with heightened OxS and platelet activation compared to aortic MPHVs. These findings may help explain the higher thrombotic risk observed with mitral valves and support differential management strategies.