Causes of macrocytic anemia among 628 patients: mean corpuscular volumes of 114 and 130 fL as critical markers for categorization

Int J Hematol. 2016 Sep;104(3):344-57. doi: 10.1007/s12185-016-2043-x. Epub 2016 Jun 28.


There have been no studies on the distribution of causes of macrocytic anemia with respect to mean corpuscular volume (MCV) cutoff values. We retrospectively investigated the causes of macrocytic anemia (MCV ≥100 fL) among 628 patients who visited the outpatient hematology clinic in Tohoku University Hospital. To ensure data validity, we also analyzed data from 307 patients in eight other hospitals in the Tohoku district. The leading causes of macrocytic anemia (number of patients, %) were myelodysplastic syndromes (121, 19.3 %), suspected bone marrow failure syndromes (BMF; 74, 11.8 %), aplastic anemia (51, 8.1 %), plasma cell dyscrasia (45, 7.2 %), and vitamin B12 deficiency (40, 6.4 %) in Tohoku University Hospital. We made three primary findings as follows. First, the most common cause of macrocytic anemia is BMF. Second, lymphoid and solid malignancies are also common causes of macrocytosis. Third, macrocytic anemia may be classified into three groups: Group 1 (megaloblastic anemia and medications), which can exceed MCV 130 fL; Group 2 (alcoholism/liver disease, BMF, myeloid malignancy, and hemolytic anemia), which can exceed MCV 114 fL; and Group 3 (lymphoid malignancy, chronic renal failure, hypothyroidism, and solid tumors), which does not exceed MCV 114 fL. These conclusions were supported by the results from eight other hospitals.

Keywords: Bone marrow failure syndromes; MCV; Macrocytic anemia; Megaloblastic anemia; Solid tumors.

MeSH terms

  • Anemia, Aplastic
  • Anemia, Macrocytic / blood
  • Anemia, Macrocytic / classification
  • Anemia, Macrocytic / etiology*
  • Anemia, Macrocytic / pathology
  • Anemia, Megaloblastic
  • Bone Marrow Diseases
  • Bone Marrow Failure Disorders
  • Erythrocyte Indices
  • Hemoglobinuria, Paroxysmal
  • Humans
  • Neoplasms / complications
  • Retrospective Studies

Supplementary concepts

  • Bone Marrow failure syndromes