Anemia increases the risk of venous thromboembolism? Insights from genome-wide association studies

Venous thromboembolism (VTE) is a significant global health concern. Recent investigations indicate that anemia may increase the risk of VTE. Nevertheless, the presence of confounding variables in observational studies has rendered the causal association between anemia and VTE inconclusive. This study utilized a two-sample Mendelian Randomization methodology, employing genetic variants derived from specific large-scale genome-wide association studies as instrumental variables to investigate the causal relationship between anemia and VTE. Rigorous statistical analyses were conducted, including the primary analysis based on the inverse-variance weighted (IVW) method, along with supplementary analyses such as MR-Egger, weighted median, and MR-PRESSO, to ensure the reliability and validity of our results. Our analysis suggests a potential causal association between anemia and certain thrombotic events. Anemia was associated with an increased risk of thrombosis and embolism in unusual sites (OR = 1.446, 95% CI: 1.104–1.895, <i>p</i> = 0.007), while aplastic anemia showed a weak positive association with overall VTE risk (OR = 1.065, 95% CI: 1.003–1.131, <i>p</i> = 0.040). Anemia individuals face an increased risk of embolism and thrombosis events, and AA exhibits a potential association with VTE. Nevertheless, a comprehensive comprehension of the precise underlying mechanisms linking anemia/AA and VTE necessitates further exploration through supplementary research. Schematic representation of the two-sample MR analysis assessing the causal effects of anemia and its subtypes (IDA, HHA, AA) on VTE and related thrombotic outcomes (PE, DVT, PVT, and other embolism and thrombosis), using SNPs as instrumental variables. <b>Abbreviations:</b> AA, aplastic anemia; DVT, deep vein thrombosis; HHA, hereditary hemolytic anemias; IDA, iron-deficiency anemia; MR, Mendelian randomization; PE, pulmonary embolism; PVT, portal vein thrombosis; VTE, venous thromboembolism.