A 45–year–old black female presented with 2 weeks history of worsening fatigue, malaise, shortness of breath upon exertion and dizziness. She also reported irregular menstrual periods. Laboratory analysis showed: Leukocyte count 2.36 × 103/mL, Platelet count 97 × 103/mL, Hemoglobin 5.8 g/dL, Mean Corpuscular Volume (MCV) 91.1 fL, and Red Cell Distribution Width (RDW) 31.9%. Iron studies were normal. Peripheral blood smear showed schistocytosis, anisocytosis, and poikilocytosis with hypersegmented neutrophils. Other test revealed: Lactated dehydrogenase (LDH) level 4632 IU/L, Total Bilirrubin 2.3 mg/dL, Haptoglobin 26 mg/dL, Corrected Reticulocyte count 0.53%, Vitamin B12 level 153 pg/mL, Folate level 413 ng/mL, Homocysteine level 73.3 mmol/L, and Methylmalonic Acid (MMA) 60.93 mmol/L. Hemoglobin electrophoresis and G6PD screen were normal. Direct Coombs and fecal occult blood were negative. Pelvic sonogram revealed a normal endometrium and a normal sized uterus with a small fibroid. Bone Marrow aspiration and biopsy showed hypercellularity with megaloblastic changes. Flow cytometry showed no evidence of increase blast cells. Anti–intrinsic Factor Antibody was positive, hence, a diagnosis of Pernicious Anemia was made. Treatment with Vitamin B12 injections resulted in normalization of the pancytopenia, LDH, Bilirrubin and trasaminases levels.
Intramedullary hemolysis can result in severe anemia in patients with Vitamin B12 Deficiency. Although this patient presented with irregular menstrual periods and anemia with elevated RDW, her normal iron indices and normal endometrial thickness, excluded the diagnosis of Iron Deficiency Anemia. Schistocytosis, high LDH and low Haptoglobin pointed towards hemolysis, and the low Reticulocyte count indicated an inadequate bone marrow response to the anemia. The hypercellular bone marrow with megaloblastic changes and the peripheral smear with hypersegmented neutrophils indicated Folic Acid or Vitamin B12 Deficiency. The patient’s low normal Vitamin B12 with high MMA levels and a positive Anti–intrinsic Factor Antibody, demonstrated she had Vitamin B12 Deficiency due to Pernicious Anemia, resulting in severe intramedullary hemolysis and ineffective erythropoiesis. Although Vitamin B12 Deficiency normally presents with high MCV, in this case, the normal MCV could be explained by average size of macrocytes and schistocytes.
Clinicians should consider vitamin B12 deficiency anemia in differential when working up hemolytic anemia.
Figure 1Peripheral Smear.
Figure 2Bone Marrow Biopsy.