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

Megaloblastic anemia may present with biochemical features suggestive of hemolysis, creating diagnostic uncertainty. We describe two middle-aged women who presented with severe symptomatic macrocytic anemia, markedly elevated lactate dehydrogenase (LDH), undetectable haptoglobin, and low reticulocyte counts. Further investigation confirmed a combined vitamin B12 and folate deficiency. No definitive underlying cause was identified, although long-term proton pump inhibitor (PPI) use was considered a potential contributing factor to vitamin B12 deficiency. Both patients were treated with vitamin replacement therapy and discontinuation of PPI therapy, resulting in rapid clinical and hematological improvement. These cases highlight that combined vitamin B12 and folate deficiency may mimic hemolytic anemia and that the combination of elevated LDH, low haptoglobin, and a low reticulocyte count should raise suspicion of ineffective erythropoiesis rather than true hemolysis.