CureusSevere Combined Vitamin B12 and Folate Deficiency Presenting With Features Suggestive of Hemolytic Anemia in Two Long-Term Proton Pump Inhibitor Users: A Case Report

🧩 Diagnostic Reasoning Exercise / Teaching Case

Two middle-aged women receiving long-term proton pump inhibitor therapy presented with severe macrocytic anemia, markedly elevated LDH, undetectable haptoglobin, and surprisingly low reticulocyte counts. Initial laboratory findings suggested hemolysis before combined vitamin B12 and folate deficiency was identified.

Diagnostic Considerations

• Elevated LDH and low haptoglobin can reflect ineffective erythropoiesis rather than peripheral hemolysis.
• Low reticulocyte counts provided a key clue against autoimmune or microangiopathic hemolytic processes.
• Peripheral smear findings showed macrocytosis, hypersegmented neutrophils, and megaloblastic changes.
• Long-term PPI exposure was considered a potential contributor to vitamin B12 deficiency.

Practice Pearls

• Recognize low reticulocyte counts as a potential discriminator from true hemolysis.
• Interpret macrocytic anemia alongside vitamin B12 and folate testing early.
• Review medication histories for prolonged proton pump inhibitor exposure.
• Consider ineffective erythropoiesis when hemolytic markers appear discordant.