Makrocytosis

Macrocytosis, sometimes spelled makrocytosis, is a morphological finding in which erythrocytes (red blood cells) are larger than normal. It is defined by an increased mean corpuscular volume (MCV) on a complete blood count, typically MCV greater than 100 femtoliters.

Macrocytosis occurs through two main patterns. In megaloblastic macrocytosis, impaired DNA synthesis causes delayed nuclear maturation and enlarged, oval erythrocytes, often with hypersegmented neutrophils. Non-megaloblastic macrocytosis occurs without DNA synthesis impairment and is seen in liver disease, chronic alcohol use, hypothyroidism, reticulocytosis, or with certain drugs. Reticulocytosis itself can contribute because immature red cells are larger.

Common causes include deficiency of vitamin B12 or folate (megaloblastic anemia), liver disease, chronic alcohol use, hypothyroidism, medications such as methotrexate, hydroxyurea, zidovudine, and some anticonvulsants, reticulocytosis from recent blood loss or hemolysis, myelodysplastic syndromes, and pregnancy.

Diagnosis is established by CBC showing MCV >100 fL; peripheral blood smear may show macro-ovalocytes and hypersegmented neutrophils in megaloblastic cases. Workup typically includes measurement of serum B12 and folate, liver function tests, thyroid-stimulating hormone, reticulocyte count, and review of medications; bone marrow examination may be considered if macrocytosis persists with cytopenias.

Management focuses on treating the underlying cause. B12 or folate supplementation for deficiencies; addressing alcohol use and liver disease; adjusting or stopping causative medications. Macrocytosis often improves with appropriate treatment and may resolve, but persistent macrocytosis warrants further evaluation for conditions such as myelodysplastic syndromes.