Anemia as a Potent and Underrecognized Driver of Venous Thromboembolism: A Systematic Review

<b>Background</b>: Nutritional deficiency anemias-including iron, vitamin B12, and folate deficiencies-are common worldwide and are increasingly recognized as potential contributors to venous thromboembolism (VTE). Mechanistic and epidemiologic data suggest that anemia may promote thrombosis through hypoxia, endothelial activation, reactive thrombocytosis, and hyperhomocysteinemia. However, a focused synthesis of clinical and genetic evidence specifically linking nutritional deficiency anemia to VTE has been lacking. <b>Methods:</b> We conducted a systematic search of PubMed and the Cochrane Library from inception to 30 September 2025 to identify studies assessing nutritional deficiency anemia in relation to VTE outcomes. Eligible studies included observational designs, case reports, case series, and Mendelian randomization (MR) analyses. Quality assessment followed the Newcastle-Ottawa Scale (NOS), Joanna Briggs Institute (JBI) checklists, and ROB-MR. The review was registered in PROSPERO (CRD420251235479). <b>Results:</b> Seven studies met the inclusion criteria. Observational analytical studies consistently showed that anemia was associated with adverse VTE-related outcomes. Lower hemoglobin predicted higher short-term mortality in acute pulmonary embolism (HR 1.16 per 1 g/dL decrease), increased symptomatic VTE among hospitalized patients (RR 1.94), and greater long-term bleeding and mortality risk in VTE cohorts (HRs 1.41-2.89). Iron-deficiency anemia increased the odds of VTE in population-based data (OR 1.43), and case reports described unprovoked DVT in young adults with moderate to severe anemia. The MR study indicated a potential causal association between anemia traits and thrombosis at unusual anatomical sites (OR 1.446). No study demonstrated a significant association with recurrent VTE. Most analytical studies were rated as good-high quality. <b>Conclusion:</b> Across multiple study designs, anemia-particularly iron-deficiency anemia and low baseline hemoglobin-appears to be an underrecognized factor associated with elevated VTE risk and adverse VTE-related outcomes. However, direct evidence for vitamin B12- and folate-deficiency anemia remains limited, and further well-designed prospective studies are required to confirm causality and clarify the contribution of specific nutritional deficiency subtypes, as well as to support integration of anemia assessment into VTE risk models.