Megaloblastic anemia

Causes and risk factors

The most common causes are inadequate intake, impaired absorption, or increased requirement for key vitamins needed for DNA synthesis. Deficiencies of folate (vitamin B9) and vitamin B12 are central; other rare causes include certain medications and inherited defects of nucleotide metabolism. For general information on vitamins and nutrition see vitamins.

Pathology and characteristics

When folate or vitamin B12 are lacking, cell division in the marrow slows while cell growth continues, producing large red cell precursors with abnormal nuclei. Peripheral blood shows macrocytic (large) red cells and often a low reticulocyte count. Bone marrow examination, when performed, reveals hypercellularity with megaloblastic changes.

Symptoms, signs, and diagnosis

Symptoms overlap with other anemias and can include fatigue, pallor, shortness of breath, and palpitations. Vitamin B12 deficiency may also cause neurological features such as numbness, balance problems, or cognitive changes. Clinicians use blood counts, mean corpuscular volume, peripheral smear, and targeted assays of folate and vitamin B12 to reach a diagnosis.

Treatment and prevention

Management depends on the cause. Replacement therapy with folic acid or vitamin B12 relieves hematologic abnormalities; however, isolated folic acid can mask B12 deficiency and allow neurologic damage to progress. Addressing malabsorption, dietary insufficiency, or medication causes is essential. For resources on vitamin B12 specifically see vitamin B12.

Notable distinctions

Megaloblastic anemia is distinct from other macrocytic anemias caused by alcohol, liver disease, or hypothyroidism, which may share large red cells but differ in underlying mechanisms and management. Timely diagnosis is important because hematologic and neurologic outcomes are often reversible with appropriate therapy.