What is Macrocytosis?
Macrocytosis is a condition where red blood cells are larger than normal. The size of these blood cells is measured in a routine blood test, or complete blood count (CBC), with a point called mean corpuscular volume (MCV). Often, a situation called elevated mean corpuscular hemoglobin can be linked to increased MCV values. Both of these factors suggest the presence of macrocytosis.
In some instances, finding macrocytosis may not require further evaluation or treatment. However, it’s important to understand that macrocytosis could potentially lead to a significant form of anemia (macrocytic anemia). It’s also critical to remember that macrocytosis can sometimes indicate issues with organ systems other than the blood.
Paying careful attention to the patient’s medical history, physical examination, and laboratory findings helps doctors identify the root cause of macrocytosis. This information guides them to the best course of treatment for their patients.
What Causes Macrocytosis?
Macrocytosis, a condition where red blood cells are larger than normal, can be caused by several things. In many cases, it’s due to issues with how red blood cells are developed or composed, or a high number of reticulocytes, which are immature red blood cells.
For instance, deficiencies in vitamin B12 or folate might cause improper red blood cell development. If you’ve been following a strictly vegan diet for a long time, you might be deficient in vitamin B12, because the body relies on the stomach and small intestine to absorb it. If your immune system interferes with the absorption process, you won’t get enough of the vitamin. Similarly, gastrointestinal issues like pernicious anemia, gastritis, celiac disease, inflammatory bowel disease, or surgeries like gastrectomy, gastric bypass, and ileal resection can impair vitamin B12 absorption. Certain medications like proton pump inhibitors and metformin or abuse of substances like nitrous oxide can also affect absorption.
Folate deficiency is another potential cause, especially in elderly people or those who consume a lot of alcohol. Like vitamin B12, folate needs a healthy small intestine to be absorbed properly. Your ability to absorb folate might be impaired if you have intestinal issues like celiac disease, inflammatory bowel disease, or if you’ve undergone small bowel resection. Certain medications, like methotrexate, phenytoin, and trimethoprim can interfere with folate metabolism, as can alcohol. Moreover, your body needs more folate when you’re pregnant or if you have chronic hemolysis, which is the destruction of red blood cells.
When your body has a high number of reticulocytes, it can also lead to macrocytosis since these immature red blood cells are quite large. This might occur in response to some types of anemia or during the recovery from conditions that hinder red blood cell production.
Other conditions that are believed to cause macrocytosis but aren’t fully understood include hypothyroidism, pregnancy, liver disease, Down syndrome, HIV, multiple myeloma, and hereditary stomatocytosis. Certain medications such as valproic acid, hydroxyurea, allopurinol, and reverse-transcriptase inhibitors like zidovudine, stavudine, and lamivudine may also cause macrocytosis.
It’s worth noting that lab test results may show an elevated MCV (measure of the average size of your red blood cells) for various reasons unrelated to macrocytosis, such as cold agglutinins (substances that cause red blood cells to clump together) or other inflammatory or neoplastic conditions. Having a high white blood cell count or high blood sugar levels might also lead to an overestimation of MCV.
Risk Factors and Frequency for Macrocytosis
Macrocytosis is a condition that is found in about 1.7% to 3.9% of people. It tends to affect males more, and it’s also more common in older individuals. It’s important to note that around 40% of people with macrocytosis also have anemia, a lack of healthy red blood cells. Furthermore, if a person with macrocytosis has anemia, there’s an increased likelihood that they might have a primary bone marrow disease.
Signs and Symptoms of Macrocytosis
Macrocytosis is a condition where your red blood cells are larger than usual. It’s often detected during routine blood tests and most people might not have symptoms or even know they have it. However, in some instances, macrocytosis could hint at an underlying medical condition. A detailed medical history and physical exam are crucial to identify possible reasons for this condition.
If the macrocytosis is accompanying anemia (low red blood cell count), people might feel tired, have difficulty breathing, feel lightheaded, experience palpitations, or even faint. These are all signs of anemia. Pale skin or abnormally pale mucous membranes (the moist lining of some parts of the body such as the nose and mouth) could also suggest anemia. Rapid heart rate could be a sign of severe anemia.
Doctors should get to know about all current and past medicines you’ve taken because certain medications could lead to macrocytosis. They’ll speak to you about your alcohol intake and diet as well, as your eating habits might suggest a lack of nutrients like folate and vitamin B12 – both important for red blood cells.
- Tiredness, difficulty breathing, heart palpitations, lightheadedness, or fainting (anemia symptoms)
- Pale skin or mucous membranes
- Rapid heart rate
- All medications you take or have recently taken
- Alcohol consumption
- Diet including the intake of folate and vitamin B12
On the other hand, if you have tingling sensations or impaired feeling of position in your extremities, it could suggest a vitamin B12 deficiency, which can result in macrocytosis. Findings like inflammation of the tongue (glossitis), signs of liver disease like jaundice, flush areas on the skin (telangiectasias), buildup of fluid in the abdomen (ascites) and tremors, could also be indicative of macrocytosis due to liver dysfunction. Swollen lymph nodes, enlarged liver or spleen, bone tenderness might point towards cancers like multiple myeloma. Some other findings like small, red or purple spots on the skin (petechiae), bruising, or nosebleeds could indicate a low platelet count or platelet function issue often seen with macrocytic anemia due to issues in the bone marrow.
Testing for Macrocytosis
If your complete blood count test shows a high mean corpuscular volume (MCV), this indicates that you may have a condition called macrocytosis, which means your red blood cells are larger than normal. To confirm this, your doctor might examine a sample of your blood under a microscope, a procedure known as a peripheral blood smear. This might reveal a condition known as megaloblastic change which affects the structure of your red blood cells.
There are several things your doctor might look for in your blood smear. For example, they may look for ‘target cells’, which can sometimes indicate liver disease. However, this isn’t a specific sign, meaning that it could indicate several different health problems, not just liver disease.
In order to pinpoint the cause of macrocytosis, your doctor may order additional tests. These might include a reticulocyte count (a measure of young red blood cells), levels of vitamin B12 and folate which are necessary for red blood cell production, methylmalonic acid and homocysteine levels for metabolism health, iron studies to check your body’s iron level, thyroid stimulating hormone (TSH) and free T4 levels for thyroid function, and liver and kidney function tests. They may also test for antibodies related to the HIV virus, and conduct a urinalysis to check for protein in your urine.
Depending on your results, your doctor may also conduct more specific tests to confirm a suspected cause. For example, if they suspect vitamin B12 deficiency, they may do a Schilling test to check how well your body can absorb this vitamin. If their suspicion is multiple myeloma, a type of cancer, a serum protein electrophoresis might be done. If they can’t determine the cause or if you have decreased levels of all blood cell types (pancytopenia), they might need to take a small sample of your bone marrow for testing.
Extra care is needed when assessing people who are at risk of iron deficiency or chronic diseases, such as cancer or inflammatory conditions. These conditions can sometimes make the MCV normal, making it harder to identify the underlying issue causing macrocytosis.
Treatment Options for Macrocytosis
Macrocytosis, a condition where red blood cells are larger than normal, can be managed differently based on its cause and whether it’s associated with anemia, a shortage of red blood cells. If the change in red blood cell size is relatively minor (with an MCV, or mean corpuscular volume, less than 115) and there isn’t a major drop in red blood cell count and the patient doesn’t exhibit worrying characteristics after a detailed disease history review, physical exam, and initial laboratory tests, no treatment might be needed.
If the person often drinks alcohol, macrocytosis and a correlating type of anemia might go away several months after they stop drinking alcohol. Changes in the bone marrow caused by alcohol can also reverse. Although in this case macrocytosis might not have a direct impact, reducing alcohol use can prevent issues like worsening liver disease, nutritional deficiencies, high blood pressure, inflammation of the pancreas, and mental health disorders.
If anemia is severe or the MCV is 115 or higher, more investigation should be done to figure out the cause. It’s the cause that will determine the best treatment approach. If the individual is deficient in vitamin B12, they can take supplements by mouth. If the body isn’t absorbing the vitamin properly, it may be given with an intramuscular injection monthly. Folic acid might be prescribed to be taken orally every day. If certain medications are causing the problem, dosage adjustments or stopping them might be necessary, depending on the doctor’s advice.
If the cause is a gastrointestinal issue preventing optimal absorption of nutrients, appropriate treatment should be identified with a relevant specialist referral. In cases where the cause might be abnormal cell growth or a blood cancer, the patient might need an oncology referral.
What else can Macrocytosis be?
Macrocytosis is a term that represents larger-than-normal red blood cells. It can be caused by a variety of things; doctors call all these possible causes ‘the differential diagnosis.’ However, sometimes what looks like macrocytosis is actually something called pseudomacrocytosis. Pseudomacrocytosis can be caused by a few factors:
- Red blood cells clumping together in the test tube or on the blood smear, which can happen if you have cold agglutinins, immune disorders, or if the anticoagulant in the test tube isn’t working properly.
- Severe high blood sugar (hyperglycemia).
- An extremely high white blood cell count (leukocytosis).
These conditions can make the red blood cells appear larger than they really are, which is why it’s called pseudomacrocytosis (pseudo means false). You can usually see these changes on a blood smear.
What to expect with Macrocytosis
The outlook or prognosis for someone’s recovery can change based on the cause of their symptoms and other health conditions they may have. For instance, patients who have an enlarged red blood cell condition called macrocytic anemia together with chronic kidney failure tend to have the lowest survival rates, which is about 40% after 5 years. Also, individuals with nutritional deficiencies have relatively poor survival chances, about 52%.
If macrocytic anemia is caused by a mix of factors, like medication reactions, survival rates tend to be higher. Similarly, if the condition is due to alcohol use, and there is no severe anemia or liver disease, the condition is relatively harmless and the prognosis is generally better.
Possible Complications When Diagnosed with Macrocytosis
Like other types of anemia, macrocytic anemia can lead to decreased exercise capabilities and functional level, lower physiological backup during acute illness or physical harm, and higher chances of death from any cause. However, macrocytosis, on its own, has no known direct complications.
Effects of Macrocytic Anemia:
- Decreased ability to exercise
- Reduced functional level
- Lower physiological backup during acute illness or injury
- Increase in all-cause mortality
Note: Macrocytosis itself does not cause any direct complications.
Preventing Macrocytosis
If you don’t have anemia or any other alarming signs based on your reports, medical history and physical examination, don’t worry too much about a slightly high MCV – it’s relatively common in healthy individuals. MCV, or Mean Corpuscular Volume, is a measure of the average size of your red blood cells. If you’re someone who drinks alcohol regularly, even if your other lab tests look fine and there’s no other sign of liver disease, you should be aware that this could be an early warning sign of too much drinking. Your doctor will talk with you about any other unusual findings in your examination and testing, as these will guide the next steps in your treatment plan.
