From the Guidelines
Macrocytosis without anemia is most commonly caused by factors such as alcohol consumption, certain medications, liver disease, hypothyroidism, vitamin B12 or folate deficiency, myelodysplastic syndromes, and reticulocytosis. These conditions can lead to an increase in mean corpuscular volume (MCV) without a significant decrease in hemoglobin levels. Some of the key causes include:
- Alcohol consumption, which directly affects red blood cell membrane formation 1
- Certain medications, such as anticonvulsants, chemotherapy agents, and antiretrovirals, that interfere with DNA synthesis in developing red blood cells 1
- Liver disease, which affects cell membrane composition 1
- Hypothyroidism, which slows cellular metabolism and red cell turnover 1
- Vitamin B12 or folate deficiency, which may show macrocytosis before anemia develops 1
- Myelodysplastic syndromes, which cause abnormal blood cell production 1
- Reticulocytosis, which occurs during recovery from blood loss or hemolysis 1 It's essential to note that some medications, such as azathioprine and 6-mercaptopurine, can induce macrocytosis through myelosuppressive activity 1. Diagnosis typically involves a complete blood count, peripheral blood smear, liver function tests, thyroid studies, and vitamin level measurements to determine the specific cause while the patient may remain asymptomatic from a hematologic perspective. In patients with inflammatory bowel disease (IBD), folate deficiency can be caused by low intake, malabsorption, excess folate utilization due to mucosal inflammation, and medications 1. The most recent and highest quality study recommends monitoring iron status and folate levels in IBD patients who are pregnant and supplementing with iron and/or vitamin B9/folic acid in case of deficiencies 1.
From the Research
Causes of Macrocytosis without Anemia
Macrocytosis, defined as a mean corpuscular volume (MCV) greater than 100 fL, can occur without anemia. The causes of macrocytosis without anemia are varied and can be categorized into several groups:
- Alcohol abuse: Studies have shown that alcohol abuse is a common cause of macrocytosis without anemia 2.
- Liver disease: Liver disease can cause macrocytosis due to impaired liver function and altered lipid metabolism 3.
- Hypothyroidism: Hypothyroidism can cause macrocytosis due to decreased thyroid hormone production and altered metabolism 3.
- Primary bone marrow disorders: Primary bone marrow disorders, such as myelodysplastic syndrome (MDS) and myeloproliferative disorders, can cause macrocytosis without anemia 4, 3.
- Medications: Certain medications, such as those used to treat cancer and autoimmune disorders, can cause macrocytosis without anemia 3.
- Unknown causes: In some cases, the cause of macrocytosis without anemia may be unknown, and further evaluation and follow-up may be necessary to determine the underlying cause 4.
Evaluation and Diagnosis
The evaluation and diagnosis of macrocytosis without anemia involve a combination of laboratory tests, medical history, and physical examination. The following tests and evaluations may be useful:
- Complete blood count (CBC) to determine the MCV and rule out anemia
- Reticulocyte count to evaluate bone marrow function
- Peripheral smear to evaluate erythrocyte and leukocyte morphology
- Vitamin B12 and folate levels to rule out deficiency
- Liver function tests to evaluate liver function
- Thyroid function tests to evaluate thyroid function
- Bone marrow biopsy to evaluate bone marrow function and rule out primary bone marrow disorders 4, 3.