Elevated plasma vitamin B12 levels and risk of venous thromboembolism among cancer patients: A population-based cohort study

- Both venous thromboembolism and high vitamin B12 mark occult and aggressive cancer.
- No previous association between the two has been shown.
- Danish health registries provided data to this cohort study.
- High vitamin B12 was associated with venous thromboembolism in cancer patients.

IntroductionBoth venous thromboembolism (VTE) and high plasma vitamin B12 levels (cobalamin, Cbl) are markers of occult cancer and aggressive cancer with a poor prognosis. In this population-based cohort study, we assessed VTE risk among cancer patients with high plasma Cbl levels.Materials and methodsWe used Danish health registries to identify a Cb1 cohort of 25,310 cancer patients with a plasma Cbl measurement prior to cancer diagnosis. The cohort was subdivided according to Cbl levels (pmol/L): 200-600 (population reference range), 601-800 and > 800. All VTE events were considered provoked and categorised as either cancer-associated if no other provoking factors were present before VTE or provoked by other risk factors (surgery, trauma, or pregnancy). We calculated cumulative incidence proportions and adjusted hazard ratios computed from Cox regression analysis (reference: plasma Cbl of 200-600 pmol/L) for the risk of VTE before and after the cancer diagnosis date (index date).ResultsThe risk of cancer-associated VTE 30 days after index date increased with higher Cbl levels. The cumulative incidence (95% CI) by Cbl levels was: 200-600 pmol/L: 0.24 (0.18-0.31); 601-800 pmol/L: 0.63 (0.34-1.09); > 800 pmol/L: 0.86 (0.49-1.40). Adjusted hazard ratios (95% CI) were: 601-800 vs. 200-600: 2.55 (1.32-4.92); > 800 vs. 200-600: 2.36 (1.19-4.71). We found similar results for VTE provoked by other risk factors and for VTE occurring before index date, but scarcity of events produced uncertain risk estimates.ConclusionWe demonstrated an association between high plasma Cbl levels and risk of VTE in cancer patients. Any clinical implications warrant further study.