Differential Diagnosis for Persistent Elevated MCV with Normal Hgb

Single Most Likely Diagnosis

• Vitamin B12 or Folate Deficiency: This is the most common cause of elevated Mean Corpuscular Volume (MCV) with normal hemoglobin (Hgb) levels. Deficiencies in either vitamin B12 or folate can lead to impaired DNA synthesis, resulting in the production of larger than normal red blood cells (macrocytosis) without necessarily causing anemia.

Other Likely Diagnoses

• Alcohol Abuse: Chronic alcohol consumption can lead to macrocytosis due to its toxic effects on the bone marrow, leading to the production of larger red blood cells. Alcohol abuse can also lead to nutritional deficiencies, including vitamin B12 and folate deficiency.
• Hypothyroidism: Some cases of hypothyroidism can present with macrocytic anemia or elevated MCV without significant anemia. The mechanism is not fully understood but may involve decreased metabolism and altered lipid metabolism affecting red blood cell membranes.
• Liver Disease: Certain liver diseases, such as cirrhosis, can cause macrocytosis. The liver plays a role in lipid metabolism, and abnormalities can affect the red blood cell membrane, leading to larger cells.

Do Not Miss Diagnoses

• Myeloproliferative Neoplasms (e.g., Polycythemia Vera, Essential Thrombocytosis): Although these conditions more commonly present with elevated blood cell counts, some cases can have a macrocytic component. Missing these diagnoses could lead to significant morbidity and mortality due to the risk of thrombosis and transformation to acute leukemia.
• Paroxysmal Nocturnal Hemoglobinuria (PNH): A rare, acquired, life-threatening disease of the blood characterized by the destruction of red blood cells, bone marrow failure, and the potential for thrombotic events. Macrocytosis can be a feature, and missing this diagnosis could be fatal.

Rare Diagnoses

• 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 often macrocytosis.
• Pharmaceutical Causes: Certain medications, such as hydroxyurea, azathioprine, and some anticonvulsants, can cause macrocytosis as a side effect. While not rare in the context of patients taking these medications, they are less common causes overall.