Vitamin B12 deficiency: This is often the most common cause of macrocytic anemia due to the crucial role of vitamin B12 in DNA synthesis. A deficiency leads to ineffective erythropoiesis, resulting in large, immature red blood cells.

Folate deficiency: Similar to vitamin B12, folate is essential for DNA synthesis. Its deficiency can lead to macrocytic anemia, often seen in pregnancy, alcoholism, or with certain medications.
Alcoholism: Chronic alcohol abuse can lead to macrocytic anemia through multiple mechanisms, including direct toxicity to the bone marrow, folate deficiency, and liver disease.
Hypothyroidism: Although less common, hypothyroidism can cause macrocytic anemia, possibly due to decreased erythropoiesis and altered lipid metabolism.

Pernicious anemia: An autoimmune condition leading to vitamin B12 deficiency due to the lack of intrinsic factor, necessary for B12 absorption. It's crucial to diagnose as it requires specific treatment.
Bone marrow disorders (e.g., myelodysplastic syndromes): These conditions can present with macrocytic anemia and have significant implications for prognosis and treatment.
Medication-induced macrocytosis: Certain drugs, such as methotrexate, can cause macrocytic anemia. Recognizing these side effects is essential for managing patients on long-term medications.

Orotic aciduria: A rare genetic disorder affecting pyrimidine synthesis, leading to macrocytic anemia.
Congenital dyserythropoietic anemias: A group of rare genetic disorders characterized by ineffective erythropoiesis and macrocytosis.
Liver disease: Although more commonly associated with other types of anemia, severe liver disease can rarely cause macrocytic anemia due to impaired liver function affecting folate and vitamin B12 metabolism.