Overview

Macrocytosis is a term used to describe erythrocytes or red blood cells that are larger than normal, it is typically found on routine examination when you do a complete blood count (CBC), macrocytosis is reported as mean cell volume or mean corpuscular volume (MCV), which describes the average size of your red blood cells, you have macrocytosis if your MCV is higher than 100 fL or femtoliters.¹

Macrocytosis isn’t always a sign of a serious underlying condition and may not need further investigations and management, but your healthcare provider may be concerned about the existence or development of anaemia (macrocytic anaemia), or other underlying conditions that necessitate timely and efficient management.

Macrocytosis isn’t a disease or a condition on its own, so there are no signs and symptoms. The only sign of macrocytosis is an increased mean corpuscular volume. If there are any other signs and symptoms, they are typically related to the underlying cause of macrocytosis.

Causes of macrocytosis

Any problem or abnormality in the production or structure of the red blood cells can lead to macrocytosis, also the presence of immature red blood cells (reticulocytes) in your blood can reflect as macrocytosis due to the fact that reticulocytes are larger in size in mature blood cells (erythrocytes). In some cases, the presence of an underlying condition could be the cause of macrocytosis. Specific causes of macrocytosis include the following:^2,3

• Vitamin B12 and folate deficiency:  To make healthy mature blood cells, your body needs nutrients like vitamin B12 and folate. Any deficiency or underlying condition that may prevent your body from absorbing these nutrients will lead to an abnormal development of red blood cells and macrocytic anaemia
• Medications: Many medications can cause macrocytosis, the most common medication that causes higher MCV is hydroxyurea for treating sickle cell disease. Chemotherapy drugs for cancer treatment and antiretroviral drugs for HIV treatment have also been associated with macrocytosis
• Alcohol abuse: Chronic abuse of alcohol is toxic and prevents your body from absorbing essential nutrients like folate needed for the production of normal red blood cells. Stopping alcohol can rapidly correct a high mean corpuscular volume
• Liver disease: Liver disease can cause macrocytosis. Sometimes liver disease and macrocytosis can be an indicator of alcohol abuse
• Reticulocytotic (haemolysis or haemorrhage): The existence of a haemolytic condition like sickle cell anaemia,glucose-6-phosphate-dehydrogenase (G6PD) deficiency, or haemorrhage and severe blood loss can cause haemolysis or immature loss of red blood cells, the bone marrow compensate this loss by releasing reticulocytes into the blood causing macrocytosis
• Myelodysplastic syndrome: It is a type of cancer that prevents the bone marrow from producing normal red blood cells
• Hypothyroidism: The condition may cause macrocytosis with or without anaemia

Diagnosis of macrocytosis

Macrocytosis isn’t a diagnosis, if your healthcare provider is concerned about the existence of an underlying disease or condition, they will investigate further by asking about your medical history including history of medications, family medical history, diet, and alcohol consumption. They may carry out the following investigations to confirm the diagnosis if they are suspecting any condition:³

• Peripheral blood smear: Your healthcare provider will examine your cells under a microscope to look for any abnormalities that can lead to macrocytosis
• Vitamin B12 and folate level: Deficiency in these nutrients can be the main cause of macrocytosis by depriving the red cells of what they need to develop healthy
• Reticulocyte count: This is to determine if the macrocytosis is due to the presence of immature blood cells
• Liver function test: To ensure that your liver is functioning well and able to absorb the nutrients needed to make healthy red blood cells
• Bone marrow biopsy: This test is carried out if your healthcare provider suspects the problem is with the production of red cells in the bone marrow. A sample of your bone marrow will be examined to confirm if there is a problem within the bone marrow

Management of microcytosis

Management of macrocytosis depends on two factors: first is the underlying cause and the second is if there is an associated anaemia. If the MCV count is < 115 and there is no anaemia, your provider will take proper history to exclude any underlying cause, if from initial history and examinations no underlying condition is suspected, no treatment is required. If the problem is alcohol abuse, the macrocytosis is usually corrected after stopping alcohol consumption.

If there is significant anaemia and the MCV count is ≥ 115, more tests should be performed to determine the cause, and accordingly the appropriate treatment.  If nutritional deficiency was found to be the cause of macrocytosis, vitamin B12 supplements may be given orally or IM monthly.  Folic acid may also be supplemented daily. In case the cause of it was any medications used, they should be withdrawn or adjusted after consulting with the specialist. Oncology referral is advised in case of malignancy.⁴

FAQS

How serious is macrocytosis?

Macrocytosis isn’t serious in most of the cases, but your healthcare provider will carry out the necessary examinations and investigations to ensure everything is fine and to manage the cause of the problem if there is any.

Does macrocytosis cause fatigue?

If the cause of macrocytosis was anaemia, you may feel fatigue and tiredness. If you notice any signs or symptoms contact your healthcare provider.

Can you reverse macrocytosis?

Yes, in most cases treating the underlying cause corrects the macrocytosis. Your doctor will ask for a complete blood count to check your MCV after you finish your treatment. Follow up and periodic check is necessary especially in cases of anaemia.

Summary

Macrocytosis is a condition characterized by the presence of abnormally large red blood cells in the blood, often detected through a complete blood count (CBC) that shows an elevated mean corpuscular volume (MCV). The diagnosis of macrocytosis involves identifying the underlying cause, which can include vitamin B12 or folate deficiency, alcohol use, liver disease, hypothyroidism, bone marrow disorders, and certain medications. To diagnose the specific cause, a thorough patient history, physical examination, and targeted laboratory tests, such as serum vitamin B12 and folate levels, liver function tests, and thyroid function tests, are essential. In some cases, a bone marrow biopsy may be necessary. Treatment of macrocytosis focuses on addressing the underlying cause. For instance, vitamin B12 or folate deficiencies are treated with appropriate supplementation. If alcohol use or medication is the cause, reducing alcohol intake or adjusting the medication may resolve the condition. Managing underlying diseases like hypothyroidism or liver disease is also crucial. In cases where a bone marrow disorder is the cause, more specialized treatments, such as bone marrow-stimulating agents or other therapies, may be required. Regular monitoring is important to ensure that the treatment is effective and that the MCV returns to normal.