Macrocytosis Clinical Presentation

Updated: Oct 07, 2022
  • Author: Vincent E Herrin, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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The symptoms of macrocytosis are attributable either to the anemia itself or to the underlying condition causing the anemia. They may include the following:

  • Dyspnea – This is a consequence of anemia; in acute or severe anemia, the volume of hemoglobin in the blood is inadequate to provide appropriate oxygenation of the tissues

  • Headache – This is a symptom of anemia due to decreased oxygenation of the tissues

  • Fatigue – This may be attributed to underlying disease, if present, or to inadequate blood volume

  • Sore tongue – This may reflect glossitis or atrophy of the tongue, which are common findings in folate and vitamin B12 deficiencies [20]

  • Diarrhea or other gastrointestinal (GI) symptoms – These may be present in patients with tropical or celiac sprue; sprue may cause folate or vitamin B12 deficiencies [21]

  • Paresthesia or gait disturbances – These suggest vitamin B12 deficiency

A history of alcohol abuse may be an important clue to the cause of the increased mean cell volume (MCV). Long-term use of alcohol may have a direct toxic effect on the bone marrow, causing macrocytosis; in addition, macrocytosis may result from poor nutritional intake in this population. [22]  An increased prevalence of depression and psychosis have been reported in patients with macrocytosis; those psychiatric disorders may share a common etiology with macrocytosis (eg, vitamin B12 deficiency). [23]

A thorough examination of the patient’s medication regimen is also crucial in the workup of macrocytosis, because a variety of medications may have an effect on the MCV. Recent acute blood loss may signal that reticulocytosis is causing the MCV increase.


Physical Examination

The following physical findings may be noted:

  • Glossitis suggests that the macrocytosis stems from deficiency of vitamin B12, folate, or both.
  • Tachycardia is usually modest and is common in patients with severe anemia.
  • Flow murmurs usually are noted only in patients with severe anemia.
  • Splenomegaly may be quite remarkable when the macrocytosis is due to hemolysis, infiltrative disorders, or neoplasms.
  • Jaundice suggests liver disease or hemolysis, both of which may lead to an increased MCV.
  • Conjunctival pallor is evident in patients with severe anemia.
  • Neurologic disorders, such as ataxia, loss of posterior column sensations, loss of deep tendon reflexes (particularly ankle reflex), and confabulation, may suggest thiamine deficiency.