Iron Deficiency Anemia with Elevated Vitamin B12

Primary Diagnostic Considerations

Inflammatory bowel disease (IBD) is a leading consideration for iron deficiency anemia with elevated vitamin B12, as it causes both iron deficiency from chronic blood loss and can present with elevated B12 levels in the context of active inflammation 1, 2.
The anaemia of chronic disease (ACD) frequently coexists with true iron deficiency in IBD, creating a mixed picture 3, 4.
Gastrointestinal cancers (colorectal, gastric) commonly present with iron deficiency from chronic occult bleeding 5, 6.
Elevated B12 can occur with various malignancies as an acute phase reactant or due to increased B12 binding proteins 2.
Hematologic malignancies including myelodysplastic syndrome should be considered, particularly if other cell lines are affected 7, 8.
Hepatic dysfunction can cause elevated B12 levels due to impaired hepatic storage and release 2.

Chronic kidney disease (CKD) causes anaemia of chronic disease and can present with functional iron deficiency, and B12 levels may be elevated due to reduced renal clearance 7.
Malabsorption syndromes (celiac disease, post-bariatric surgery) can cause iron deficiency while B12 levels may be elevated if recently supplemented 2.

Complete blood count with indices should assess MCV, MCH, RDW to confirm iron deficiency 9, 6, 8.
Reticulocyte count should be low or normal to confirm deficiency state rather than hemolysis 9, 8.
Inflammatory markers such as CRP, ESR should be assessed to evaluate for chronic inflammation 3, 4.
Transferrin saturation <16-20% confirms iron-restricted erythropoiesis 2, 3.
Comprehensive metabolic panel should assess liver and kidney function 7.
Ferritin interpretation: without inflammation, ferritin <30 μg/L confirms iron deficiency 2, 8, 10, and with inflammation, ferritin up to 100 μg/L may still indicate iron deficiency 2, 3, 8.

Do not rely on ferritin alone in inflammatory states, as it can be falsely normal or elevated despite true iron deficiency 3, 4, 6.
Do not overlook drug-induced causes, such as NSAIDs, anticoagulants, and immunosuppressants, which can contribute to both bleeding and anaemia 1, 3.
Do not miss combined deficiencies, and check folate levels and consider bone marrow evaluation if multiple cell lines are affected or if the diagnosis remains unclear after initial workup 9, 7, 8.