Not All Hemolysis Is Hemolytic: A Case of Pernicious Anemia

Vitamin B12 deficiency is classically associated with megaloblastic anemia and neurologic or neuropsychiatric manifestations; however, in rare cases, it may present with pancytopenia and laboratory features that mimic hemolytic anemia. Pernicious anemia is a common cause of vitamin B12 deficiency classically described in older adults of Northern European descent; however, it can occur across all ages and ethnic backgrounds, and demographic assumptions should not delay diagnosis. We report a 35-year-old African American man with no significant past medical history who presented with progressive weakness, decreased appetite, and fatigue. Initial laboratory evaluation revealed profound macrocytic anemia, thrombocytopenia, elevated lactate dehydrogenase, indirect hyperbilirubinemia, and low haptoglobin. Despite these findings, the reticulocyte response was inappropriately low, the direct antiglobulin test was negative, and the peripheral blood smear demonstrated no schistocytes, consistent with ineffective erythropoiesis rather than true hemolysis. Further evaluation revealed severe vitamin B12 deficiency with normal folate levels and positive intrinsic factor antibodies, and biopsy findings consistent with autoimmune metaplastic atrophic gastritis supporting a diagnosis of pernicious anemia. Treatment with intramuscular vitamin B12 resulted in rapid clinical and hematologic improvement, emphasizing the reversibility of hematologic manifestations with prompt therapy. This case highlights pernicious anemia as a reversible cause of pseudo-hemolytic anemia and underscores the importance of recognizing its distinguishing features to avoid unnecessary interventions such as plasma exchange or immunosuppressive therapy.