When B12 therapy fails: two case reports of intravenous vitamin B12 resistance in pernicious anemia

BACKGROUND: Pernicious anemia is an autoimmune disorder causing vitamin B12 deficiency resulting from impaired absorption caused by intrinsic factor absence. Positive parietal cell and intrinsic factor antibodies confirm the diagnosis. Intravenous vitamin B12 effectively treats Pernicious anemia. Severe cytopenias (anemia, thrombocytopenia, neutropenia) may result, sometimes requiring emergency care and hospitalization. CASE PRESENTATIONS: Case A: A 54-year-old male presented with six months of generalized fatigue and dyspnea on exertion. Laboratory tests revealed severe macrocytic anemia (Hb: 4.7 g/dL, MCV: 120 fL), with a peripheral blood smear showing hyper-segmented neutrophils and macro-ovalocytes, suggestive of megaloblastic anemia. Bone marrow biopsy demonstrated decreased cellularity with megaloblastic changes. Despite six-weeks of intravenous vitamin B12 therapy, there was no improvement in hematological parameters. Endoscopy revealed atrophic gastritis, and biopsy showed anti-parietal cell antibodies. Following a trial of immunosuppressive therapy with cyclosporine, no significant response was observed. Bone marrow transplantation was recommended. Case B: A 62-year-old male presented with epigastric pain, dyspepsia, fatigue, and a three-month history of anorexia. He was diagnosed with macrocytic anemia (Hb: 6.7 g/dL, MCV: 100 fL), and peripheral blood smear indicated megaloblastic changes. Bone marrow biopsy confirmed decreased cellularity and megaloblastic anemia. Despite standard intravenous vitamin B12 therapy, the patient showed no hematological improvement. Endoscopic findings revealed atrophic gastritis. Immunosuppressive therapy with cyclosporine also failed, leading to the recommendation of bone marrow transplantation. CONCLUSION: Continued efforts in understanding the pathophysiology of Pernicious anemia and autoimmune-mediated bone marrow failure syndromes may pave the way for innovative therapeutic approaches in the future.