What is Macrocytic Anemia?
Macrocytic anemia refers to a condition where the average size of red blood cells is larger than normal (often measured as over 100 fL) and anemia, where there’s less hemoglobin (a protein in red blood cells that carries oxygen) than normal. Typically, for non-pregnant females, the normal amount of hemoglobin is 12 g/dL or above; for pregnant females, it’s 11 g/dL or above; and for males, it’s 13 g/dL or above. There are two types of macrocytic anemia: megaloblastic and non-megaloblastic.
Megaloblastic anemia happens when there’s a lack of folate or vitamin B12, which impairs DNA synthesis (the process of making DNA). On the other hand, non-megaloblastic anemia can occur due to various reasons.
What Causes Macrocytic Anemia?
Megaloblastic anemia is caused by a lack of folic acid and vitamin B12. Folic acid deficiency can occur due to not eating enough (seen in conditions like alcohol abuse or malnutrition), needing more than usual (as in certain blood conditions or pregnancy), or not being able to absorb it properly (due to genetic factors, certain surgeries, or medicines like cholestyramine or metformin).
Vitamin B12 deficiency can happen because of not eating enough, not being able to absorb it properly (such as in gastric conditions like atrophic gastritis or Zollinger-Ellison syndrome, tapeworm infection, certain surgeries, or certain parts of the small intestine being removed), or if substances like nitrous oxide are present that interfere with its absorption. Certain drugs that interfere with DNA synthesis, like methotrexate or 5-fluorouracil, can also cause these deficiencies.
Non-megaloblastic anemia, which does not show oversized neutrophils, can be present in a variety of situations. Harmless conditions bring about this issue, such as alcohol consumption, a genetic disorder that affects red blood cells, hypothyroidism, liver disease, or too many new red blood cells being produced due to conditions like excessive breakdown of red blood cells (hemolysis) or an illness affecting the bone marrow.
In some cases, larger than normal red blood cells are perfectly normal and might be due to genetics, or occur in infants, people with Down Syndrome, and pregnant women. Other times, it might be due to issues with testing – for example, high blood sugar can cause the blood to thicken and make red blood cells seem larger than they are, white blood cells or certain proteins might make the sample cloudy and lead to incorrect measurements of red blood cell size, or there might be mistakes from the testing procedure itself.
Risk Factors and Frequency for Macrocytic Anemia
Macrocytosis is a condition that affects 2% to 4% of the population, and 60% of those affected also suffer from anemia. It is most commonly caused by alcohol use, followed by a lack of certain nutrients, like folate and vitamin B12, and the use of certain medications. Women in middle-age are more likely to encounter this condition due to autoimmune causes, whereas older people often get the condition due to issues like hypothyroidism and primary bone marrow disease. The risk of developing a vitamin B12 deficiency, which can lead to macrocytosis, becomes more likely in people over 60 years of age.
- Macrocytosis affects 2% to 4% of the population.
- 60% of people with macrocytosis also have anemia.
- Causes include alcohol use, lack of folate and vitamin B12, and certain medications.
- Autoimmune causes are common in middle-aged women.
- Hypothyroidism and primary bone marrow disease cause macrocytosis in older patients.
- Vitamin B12 deficiency risk is higher for patients over 60 years old.
- Mild macrocytosis is likely caused by benign conditions.
- More severe macrocytosis usually results from primary bone marrow disease or deficiencies in folate or vitamin B12.
Signs and Symptoms of Macrocytic Anemia
Macrocytic anemia is a type of blood disorder that can lead to various signs and symptoms. These depend largely on the root cause. For example, people who have low levels of Vitamin B12 may experience mood changes and neurologic issues, such as memory loss, balance problems, or numbness and tingling (paresthesias). They may also have nerve damage in their hands and feet (peripheral neuropathy). Other symptoms are often related to the specific underlying condition — things like general body symptoms from primary bone marrow disease, stomach upset because of enteral malabsorption, or a slower metabolism due to hypothyroidism.
If the macrocytic anemia is caused by a lack of folate, the symptoms will be similar, except the patient usually won’t have any neuropsychiatric complaints. The individual may also have a history of certain surgeries, such as gastric bypass for weight loss or ileal resection for disorders of the colon. Those with personal or family histories of autoimmune diseases or hemolytic anemias might be more at risk. Certain medications, excessive alcohol consumption, or a diet with limited variety (such as consuming mostly tea and toast) can also contribute to it.
During a physical exam, a doctor might find signs of anemia like pale conjunctiva (the inside of your eyelids), neurologic issues if there’s a deficiency in Vitamin B12 (like having trouble determining where your body is in space, struggling with feelings of vibration, or a positive Romberg sign). The doctor might also identify signs of the underlying disease, such as a red, shiny tongue from autoimmune atrophic gastritis, an enlarged liver or spleen from familial hemolytic anemias, skin that’s lost its color from vitiligo, or yellow skin and tiny blood vessels that resemble spiders from excessive alcohol use.
Testing for Macrocytic Anemia
If your doctor suspects you might have macrocytic anemia, which is a condition where your red blood cells are larger than normal, they will start by taking a detailed health history and conducting a physical examination. After these initial steps, they’ll order specific lab tests that include measures of your red blood cells, how fast new red blood cells are being produced (reticulocyte count), and levels of vitamin B12 in your blood.
The doctor then looks at your lab results. If they find large red blood cells but no signs of megaloblastic RBCs, which are unusually large and immature red blood cells that can be a sign of macrocytic anemia, they might order further tests. These include checking for disorders in the liver or thyroid, as these are commonly associated with this type of anemia.
If there are signs of megaloblastic RBCs, the doctor will then check the reticulocyte count. If it’s less than 1%, this means that there’s not enough new red blood cells being produced. On the other hand, a count higher than 2% could indicate that your body is producing too many red blood cells because of other health conditions like hemolysis (where red blood cells are destroyed) or hemorrhage (heavy bleeding).
The level of vitamin B12 in your blood can also provide clues. Low levels (less than 100 pg/mL) could indicate a deficiency. In cases where B12 levels are above 400 pg/mL, the doctor is likely to check your red blood cell folate level, which should not be confused with serum folate as that isn’t as sensitive a test. Low folate levels can indicate a deficiency. However, if they are normal, further tests might be required, like examining the bone marrow.
In cases where B12 levels are between 100 and 400 pg/mL, your doctor may check the levels of homocysteine and methylmalonic acid (MMA) in your blood. These are substances found in the body that use folate and vitamin B12 to help with cell metabolism. High levels of these compounds can indicate vitamin B12 or folate deficiency. If the values are normal, your doctor may consider consulting with a hematologist for further testing, including a bone marrow study.
If there are issues with the shape or size of your red blood cells or other types of blood cells, your doctor may recommend getting a specialist’s opinion. In some cases, testing for specific causes of megaloblastic anemia, such as pernicious anemia, might be based on other symptoms or presentations. Pernicious anemia is often associated with antibodies against certain proteins in the body called intrinsic factor or parietal cells. A Schilling test, which was once used to measure how well your body absorbs vitamin B12, is seldom used these days.
Treatment Options for Macrocytic Anemia
In treating a type of anemia called macrocytic anemia, doctors aim at restoring the levels of folate and vitamin B12 in the body and addressing its root cause. They may recommend folic acid supplements, typically between 1 and 5 milligrams per day. Naturally, folate-rich foods such as fortified cereals and leafy vegetables are also encouraged. If the patient is on medication that affects folate levels or if they are a pregnant woman with a history of neural tube defects or using anti-seizure medications, they should take daily supplements to prevent deficiencies.
Vitamin B12 deficiency is also a common cause of macrocytic anemia and it’s crucial not to overlook it. While treating a folate deficiency can alleviate the anemia, it won’t help the neurological effects if the cause is vitamin B12 deficiency. To address this, doctors may prescribe 1000 micrograms of oral vitamin B12 daily for a month, followed by 125 to 250 micrograms daily or administer 1000 micrograms of vitamin B12 as an injection every week for a month and then monthly to replenish vitamin B12 levels. This injection form is usually chosen for patients with a specific type of anemia called pernicious anemia or altered forms of the digestive system.
In patients who are getting vitamin B12 treatment, doctors might provide additional supplements of folate (400 micrograms to 1 g/day). After 1 to 2 weeks of treatment, the number of immature red blood cells will start to increase, which is a sign of improvement. Anemia usually goes away after 4 to 8 weeks. There is no need to constantly monitor red blood cell counts or check folate or vitamin B12 levels during active treatment. However, some doctors do yearly complete blood counts for those on long-term vitamin B12 therapy. Neurologic symptoms resulting from low levels of vitamin B12 take longer to improve. If alcohol consumption has caused the macrocytic anemia, stopping alcohol will resolve the issue.
Sometimes, macrocytosis is a result of the use of certain medications (like methotrexate or zidovudine), which alone does not require treatment beyond the usage of supplements to prevent anemia.
What else can Macrocytic Anemia be?
- Anemia caused by a lack of folate (a type of vitamin)
- Anemia caused by liver disease
- Underactive thyroid (hypothyroidism)
- A condition affecting the bone marrow (myelodysplastic syndrome)
- Alcoholism
What to expect with Macrocytic Anemia
With early detection and proper treatment of the root cause, macrocytic anemia has a very good prognosis. The need for a specialist referral is quite rare, unless the anemia is resistant to treatment or there are signs of more serious underlying conditions like myelodysplasia or leukemia.
Possible Complications When Diagnosed with Macrocytic Anemia
People with a long-term condition called megaloblastic anemia, caused by a deficiency in vitamin B12, can suffer permanent nerve damage. This nerve damage is known as subacute combined neurodegeneration. Symptoms can include coordination issues when walking, memory loss, damage to the peripheral nerves (those not in the brain or spinal cord), and mental health disturbances. If someone has a form of anemia called macrocytic anemia due to other health conditions, they may also experience complications related to those conditions.
Common Symptoms:
- Coordination issues when walking
- Memory loss
- Damage to the peripheral nerves
- Mental health disturbances
Preventing Macrocytic Anemia
Macrocytic anemia is a specific type of blood disorder that occurs when the body can’t produce enough blood cells due to a lack of important nutrients. This issue can arise if a person isn’t consuming enough of these nutrients, like folate and vitamin B12, in their diet. Some people may have a hard time absorbing these nutrients, or they might have another health condition that makes it challenging for the body to meet its nutrient needs. If you have this condition, you might feel fatigued, experience changes in your memory or mood, or feel a tingling sensation in your arms and legs. Doctors can identify this form of anemia during a routine check-up and through lab tests. Treating macrocytic anemia usually involves addressing the root cause of the nutrient deficiency and supplementing with these necessary nutrients.
