Neutropenia and anemia with reduced serum vitamin B12

Authors

  • Rajesh Krishna,

    1. Department of Haematology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, Ducane Road, London W12 0HS, UK
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  • Emma O'Donovan,

    1. Department of Haematology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, Ducane Road, London W12 0HS, UK
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  • Barbara J. Bain

    Corresponding author
    1. Department of Haematology, St Mary's Hospital Campus of Imperial College Faculty of Medicine, St Mary's Hospital, Praed Street, London, W2 1NY, UK
    • Department of Haematology, St Mary's Hospital Campus of Imperial College, Faculty of Medicine, St Mary's Hospital, Praed Street, London, W2 1NY
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  • Conflict of interest: Nothing to report

1

Illustration 1.

A 55-year-old man presented with excessive tiredness and shivering at night. Nothing of note was found on physical examination. He was known to suffer from Crohn's disease and 10 years previously had been found to be deficient in vitamin B12 and had been treated briefly. A full blood count on this occasion showed pancytopenia: WBC 0.9 × 109/l, neutrophils 0.1 × 109/l, hemoglobin concentration 8.5 g/dl, mean cell volume 96 fl and platelet count 219 × 109/l. Serum B12 was below the level that could be quantified by the laboratory, <83 ng/l (normal range 160-800), confirmed on a repeat specimen. His peripheral blood film showed occasional blast cells and no neutrophil hypersegmentation. A bone marrow aspirate showed an increase both of cytologically normal proerythroblasts and of other primitive cells that were more pleomorphic than the proerythroblasts and had less cytoplasmic basophilia. The pleomorphic cells constituted 60% of bone marrow cells. Some of the mature erythroblasts had megaloblastic features. In view of the marked reduction of serum B12, the question arose as to whether the patient had a significant B12 deficiency, a hematological malignancy or both. Careful examination of the aspirate film showed some cells to contain Auer rods (Figure: red arrow, cell containing Auer rod; black arrow, proerythroblast, May–Grünwald–Giemsa). Sudan black B (SBB) staining confirmed the presence of Auer rods (Figure, inset) and showed some blast cells to have SBB-positive granules. A confident diagnosis of acute myeloid leukemia (AML) could therefore be made. The patient received daily vitamin B12 injections for 6 days with no alteration in counts and a repeat bone marrow examination showed that megaloblasts were still present. On flow cytometry the blast cells expressed CD13, CD33, CD34, CD117, HLA-DR and myeloperoxidase.

Misdiagnosis of severe megaloblastic anaemia as erythroleukemia is a well recognized pitfall. In this patient there was the potential for misdiagnosis of AML as megaloblastic anemia. However the blood count would have been very atypical for B12 deficiency since the neutropenia was severe and yet there was no thrombocytopenia. The detection of Auer rods permitted an unequivocal diagnosis. It is quite likely that there was no tissue deficiency of B12 despite the low serum concentration. Tissue delivery of vitamin B12 depends on transcobalamin concentration whereas assays are measuring also vitamin B12 bound to haptocorrin.

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