Megaloblastic Anemia Masquerading as Hemolysis in Chronic PPI Therapy: Two Case Reports

Two middle-aged women on long-term proton pump inhibitors presented with severe macrocytic anemia and biochemical signs suggestive of hemolysis (very high LDH, undetectable haptoglobin) but showed a low reticulocyte count. Workup revealed combined vitamin B12 and folate deficiency causing ineffective erythropoiesis that mimicked hemolysis. Vitamin replacement and cessation of PPI therapy led to rapid clinical and hematologic improvement, highlighting that B12/folate deficiency can resemble hemolytic processes and that PPI use may contribute to B12 deficiency.