My patient with anemia has an abnormally high mean red blood cell corpuscular volume (MCV). What conditions should I routinely consider as a cause of his macrocytic anemia?

Anemia with mean corpuscular volume (MCV) above the upper limit of normal (usually ≥ 100 fL) is considered macrocytic anemia. The numerous causes of macrocytic anemia can be divided into major categories (1,2) (Figure 1).

First, a reticulocyte production index should be calculated and if elevated the MCV can be above the normal range due to the large size of reticulocytes. Once high MCV is not thought to be related to reticulocytosis, the majority of macrocytic anemias can be categorized according to one of two major mechanisms: 1. Liver disease; and  2. Impairment of DNA synthesis, which includes nutritional deficiencies (folate, B12), drug effect (e.g co-trimoxazole, anti-neoplastic agents and certain anti-retroviral drugs) and “idiopathic” causes (myelodysplastic syndromes).

Mild macrocytosis can also be seen in hypothyroidism and hypoproliferative anemias such as aplastic anemia.  Macrocytosis without anemia or liver disease can also be a manifestation of heavy alcohol intake.

Macrocytic anemia in liver disease is due to excess lipid deposition in the red blood cell (RBC) membrane, not impairment of DNA synthesis. Enlarged RBCs are usually round and  often have a targeted appearance in liver disease; acanthocytes (spur cells) may also be present (Fig 2). In contrast, in disorders of impaired DNA synthesis, enlarged RBCs are often oval-shaped (macro-ovalocytes) (Fig 3).

Other common abnormalities seen with macrocytic anemia include hypersegmented neutrophils (eg, induced by B12 or folate deficiency), and in the case of myelodysplastic syndromes, hypogranulated neutrophils and Pelger-Huet neutrophil abnormalities.

Bonus pearl: Did you know that the MCV unit, fL, stands for femtoliters or 1/1,000,000,000,000,000 L? 


Figure 1. Major causes of macrocytic anemia. MDS: myelodysplastic syndrome.


Macrocytic_Anemia_Figure 1

Fig 2. Round macrocytes with targeting and abundant acanthocytes (spur cells) in a patient with hepatic cirrhosis.


Macrocytic_Anemia_Figure 2

Fig 3. Oval macrocytes in a patient with large granular cell leukemia and an MCV of 125 fL who received cyclophosphamide.


  1. Ward PC. Investigation of Macrocytic Anemia. Postgrad Med 1979; 65: 203-207.
  2. Green R, Dwyre DM. Evaluation of macrocytic anemias. Semin Hematol 2015; 52: 279-286.


Contributed by Tom Spitzer, MD, Director of Cellular Therapy and Transplantation Laboratory, Massachusetts General Hospital, Boston, MA.

My patient with anemia has an abnormally high mean red blood cell corpuscular volume (MCV). What conditions should I routinely consider as a cause of his macrocytic anemia?

Should I order a blood transfusion based on the hemoglobin (Hgb) or the hematocrit (Hct)?

Despite the frequent interchangeability of Hgb (g/dL) and Hct (%) by a ratio of ~1:3, directly-measured blood Hgb levels may be preferred for assessing the need for blood transfusion for at least 3 reasons:

First, in contrast to the widely-used automated measurements of Hct, Hgb is not affected by conditions that affect the size of the RBCs or the mean corpuscular Hgb concentration (MCHC). This is because the Hct is not a direct measure of Hgb; rather it’s the proportion of blood occupied by RBCs which, in automated systems, is derived by multiplying the number of RBCs by the mean corpuscular volume (MCV).1-3

This may not be a significant issue when MCHC is normal, but when MCHC is abnormal, HCT may not accurately reflect the blood Hgb concentration. For example, in patients with hypochromic iron deficiency anemia with RBCs containing less hemoglobin (ie, low MCHC), the Hct may overestimate blood Hgb levels. Conversely in hereditary spherocytosis with its attendant low RBC volume and high MCHC, the Hct may underestimate Hgb levels.

Second, Hct results may also be more subject to technical factors in the lab. For example, blood at room temperature between 6-24 h may be associated with RBC swelling and increased Hct without any change in its Hgb concentration.4

Finally, national and international guidelines on blood transfusion generally target Hgb, not Hct results.5-7

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  1. Tefferi A, Hanson CA, Inwards DJ. How to interpret and pursue an abnormal complete blood cell count in adults. Mayo Clin Proc 2005;80:923-36.
  2. Macdougall IC, Ritz E. The Normal Haematocrit Trial in dialysis patients with cardiac disease: are we any the less confused about target hemoglobin? Nephrol Dial Transplant 1998;13:3030-33.
  3. Kelleher BP, Wall C, O’Broin SD. Haemoglobin, not haematocrit, should be the preferred parameter. Nephrol Dial Transplant 2001;16:1085-87.
  4. Hayuanta HH. Can hemoglobin-hematocrit relationship be used to assess hydration status? CDK-237/vol 43 no.2, th. 2016
  5. Blood transfusion. NICE guideline, November, 2015. uk
  6. National Blood Authority: Australia. Patient blood management, November 2016.
  7. Carson JL, Guyatt G, Heddle NM, et al. Clinical practice guidelines from the AAABB: red blood cell transfusion thresholds and storage. JAMA 2016; 316:2025-2035.


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Should I order a blood transfusion based on the hemoglobin (Hgb) or the hematocrit (Hct)?