A 55-year-old man comes to the office due to fatigue for the past month. He has also had occasional heartburn but no chronic abdominal pain. Medical history is significant for hepatomegaly due to fatty liver. He has been drinking 3-4 shots of alcohol per day for several years. He does not smoke. Physical examination reveals pallor of skin and mucous membranes, and mild hepatomegaly. Laboratory results are as follows:
Hemoglobin 8.5 g/dL Leukocytes 8,000/mm3 Mean corpuscular volume 110 fL Platelets 150,000/mm3 Blood glucose 118 mg/dL Blood urea nitrogen 16 mg/dL Creatinine 1.0 mg/dL
What is the most likely cause of anemia in this patient?
This patient's heavy alcohol use, pancytopenia, and significant macrocytosis likely has megaloblastic anemia due to nutritional folate deficiency. Folate is an essential dietary nutrient found in leafy vegetables and fortified grains; because it has relatively limited total body stores, consumption of an unbalanced or nutrient-poor diet (as is common in those with alcohol use disorder) frequently results in folate deficiency within 5-10 weeks. Alcohol also directly hastens folate deficiency by reducing folate absorption in the small intestine, impairing uptake/storage in the liver, and increasing urinary excretion.
Although many cases are asymptomatic, patients often develop clinically significant megaloblastic anemia with macrocytosis (mean corpuscular volume [MCV] often >110 µm3) and mild thrombocytopenia/leukopenia. Alcohol may also cause other hematologic abnormalities such as microcytic anemia due to gastritis or bleeding varices (iron deficiency anemia) or normocytic anemia due to direct toxic effects on the bone marrow.
(Choice A) Vitamin B12 deficiency also causes megaloblastic anemia. Although patients with heavy alcohol use can develop vitamin B12 deficiency, nutritional folate deficiency arises far more quickly (due to smaller total body stores). In addition, vitamin B12 deficiency is rare in patients with alcohol use disorder who do not have chronic pancreatitis; most cases of vitamin B12 deficiency arise in older individuals with disorders of the stomach (eg, pernicious anemia, atrophic gastritis) or small intestine that impair absorption.
(Choice C) Chronic blood loss would cause iron deficiency or microcytic (MCV <80 µm3) anemia.
(Choice D) Anemia of chronic disease usually causes normochromic, normocytic anemia.
(Choice E) Thiamine deficiency is common in alcoholics, however it is not associated with megaloblastic anemia; rather it is associated with Wernicke encephalopathy.
Educational objective:
Heavy alcohol use is a common cause of nutritional folate deficiency in the United States and would cause megaloblastic anemia.