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An elderly man with hemolysis and myelophthisic anemia

  • Author Footnotes
    1 RH and AM contributed equally to this work.
    Robert Horn
    Footnotes
    1 RH and AM contributed equally to this work.
    Affiliations
    Department of Internal Medicine, The University of Texas Health Sciences Centre at Houston, Houston, TX, USA
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  • Author Footnotes
    1 RH and AM contributed equally to this work.
    Abhishek Maiti
    Footnotes
    1 RH and AM contributed equally to this work.
    Affiliations
    Department of Internal Medicine, The University of Texas Health Sciences Centre at Houston, Houston, TX, USA
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  • Sujith V. Cherian
    Correspondence
    Corresponding author at: The University of Texas Health Science Center at Houston, McGovern School of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Suite 600, 6410 Fannin Street, Houston, TX 77030, USA.
    Affiliations
    Department of Internal Medicine, The University of Texas Health Sciences Centre at Houston, Houston, TX, USA

    Department of Critical Care, Pulmonary and Sleep Medicine, The University of Texas Health Sciences Centre at Houston, Houston, TX, USA
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  • Author Footnotes
    1 RH and AM contributed equally to this work.

      1. Case description

      A 64-year-old man with history of chronic anemia and dyspepsia presented with fatigue, exertional chest pain, pedal edema and dyspnea for 2 weeks. His temperature was 37o C, heart rate 74/min, blood pressure was 133/66 mmHg, respiratory rate 18/min, and SpO2 of 96% on ambient air. Laboratory studies showed hemoglobin of 2.73 mmol/L (Normal: 8.56–10.67 mmol/L), mean corpuscular volume (MCV) of 123 fL, platelet count on 32 × 109/L and white blood cell count of 2.8 × 109/L. His indirect bilirubin was 47.9 μmol/L (normal <18 μmol/L), lactate dehydrogenase was 104.7 μkat/L (normal: 1.4–4.1 μkat/L), reticulocyte count was 1.2%, haptoglobin level was <3.65 μmol/L (normal 3.76–25.17 μmol/L) folic acid level was 40.7 nmol/L (normal, >9.1 nmol/L), vitamin B12 was 89.9 pmol/L (normal, >221 pmol/L). Peripheral blood smear (Fig. 1) was concerning for myelophthisic anemia and hence a bone marrow biopsy was performed (Fig. 1b). What is the diagnosis?
      Fig. 1
      Fig. 1a. Peripheral blood smear (hematoxylin and eosin stain, 50× magnification) showing pancytopenia with macrocytes, dacryocytes and nucleated red blood cells; b. bone marrow biopsy (hematoxylin and eosin stain, 40× magnification) showing markedly hypercellular marrow, with erythroid hyperplasia, prominent dyspoiesis in the erythroid and megakaryocyte lineages, and no increase in blasts.

      2. Discussion

      The patient has cobalamin deficiency which was found to be secondary to pernicious anemia.
      Myelophthisic anemia is due to bone marrow invasion and displacement of immature cells into circulation, by infiltration of abnormal tissue e.g. metastatic cancer, fungal infection, and granulomatous diseases [
      • Makoni S.N.
      • Laber D.A.
      Clinical spectrum of myelophthisis in cancer patients.
      ]. Hence, finding of nucleated red blood cells (RBC) on peripheral smear is very concerning and usually triggers work-up for ominous causes of myelophthisic anemia. While, cobalamin deficiency is relatively benign and easily managed. Pernicious anemia is caused by intrinsic factor deficiency. It is a protein secreted from parietal cells of gastric mucosa, which binds ingested cobalamin and enables its absorption in distal ileum. Cobalamin deficiency leads to nuclear-cytoplasmic asynchrony resulting in megaloblastic anemia with a hypercellular marrow [
      • Toh B.H.
      • van Driel I.R.
      • Gleeson P.A.
      Pernicious anemia.
      ]. Despite the hypercellularity, erythropoiesis is ineffective as the abnormal and fragile RBC precursors' breakdown leading to intramedullary hemolysis, and resultant abnormality of hemolysis labs. While megaloblastic anemia is a universally recognized presentation of cobalamin deficiency, other features like leukoerythroblastosis, hemolytic picture, and splenomegaly are less known [
      • Halfdanarson T.R.
      • Walker J.A.
      • Litzow M.R.
      • Hanson C.A.
      Severe vitamin B12 deficiency resulting in pancytopenia, splenomegaly and leukoerythroblastosis.
      ]. These features were common knowledge in the past. However, more modern literature on cobalamin deficiency often fails to mention these aspects [
      • Halfdanarson T.R.
      • Walker J.A.
      • Litzow M.R.
      • Hanson C.A.
      Severe vitamin B12 deficiency resulting in pancytopenia, splenomegaly and leukoerythroblastosis.
      ].
      The patient was treated with vitamin B12 injections. At 9-month follow-up, he was asymptomatic with normal hemoglobin and improved MCV of 94 fL.

      Contributors

      AM provided care for the patient. All authors wrote and revised the manuscript.

      Funding information

      This report received no specific funding.

      Conflict of interests

      There are no competing interests.

      Informed consent

      Written consent to publication was obtained.

      Ethics committee approval

      Not applicable.

      References

        • Makoni S.N.
        • Laber D.A.
        Clinical spectrum of myelophthisis in cancer patients.
        Am J Hematol. 2004; 76: 92-93
        • Toh B.H.
        • van Driel I.R.
        • Gleeson P.A.
        Pernicious anemia.
        N Engl J Med. 1997; 337: 1441
        • Halfdanarson T.R.
        • Walker J.A.
        • Litzow M.R.
        • Hanson C.A.
        Severe vitamin B12 deficiency resulting in pancytopenia, splenomegaly and leukoerythroblastosis.
        Eur J Haematol. 2008; 80: 448-451