Red blood cells, also known as erythrocytes, are disc-shaped cells that play a central role in human health. Their primary function is carrying oxygen from the lungs to tissues and organs, and transporting carbon dioxide, a waste product, back to the lungs. When these vital cells are larger than their typical size, it signals an underlying health issue. This article explores reasons why red blood cells might appear larger than normal.
Understanding Macrocytosis
The medical term for larger-than-normal red blood cells is macrocytosis. This condition is typically identified during a routine Complete Blood Count (CBC). An elevated Mean Corpuscular Volume (MCV), which measures average red blood cell size, indicates macrocytosis; a normal MCV usually ranges between 80 and 100 femtoliters (fL), so a value above 100 fL indicates enlarged cells. Red blood cell size affects their ability to efficiently transport oxygen and can indicate issues with production or maturation in the bone marrow. Macrocytosis is not a disease but a sign warranting further investigation.
Nutritional Deficiencies
Common causes of large red blood cells include deficiencies in vitamin B12 and folate (vitamin B9). These nutrients are crucial for DNA synthesis in red blood cell precursors within the bone marrow. A shortage of B12 or folate impairs DNA production, delaying cell division. This causes red blood cells to grow larger before dividing, forming large, immature cells called megaloblasts.
Vitamin B12 deficiency can stem from inadequate dietary intake, common in strict vegans or vegetarians as B12 is primarily found in animal products. More frequently, it arises from malabsorption. Conditions like pernicious anemia, an autoimmune disorder preventing intrinsic factor production for B12 absorption, or gastrointestinal surgeries and Crohn’s disease can hinder absorption. Some medications, such as proton pump inhibitors and metformin, can also interfere with B12 absorption.
Folate deficiency can also result from insufficient dietary intake; folate is found in leafy green vegetables, legumes, and citrus fruits but is easily destroyed by heat and alcohol. Increased demand, such as during pregnancy, can also lead to deficiency. Malabsorption due to conditions like celiac disease, chronic alcohol abuse, and medications like methotrexate and some anticonvulsants (e.g., phenytoin) can also deplete folate levels.
Other Medical Conditions
Other medical conditions can also lead to large red blood cells. Liver disease, especially advanced stages, often causes macrocytosis. This can occur due to increased cholesterol and phospholipid deposits on red blood cell membranes, enlarging their surface area. Liver dysfunction can also contribute to folate deficiency, further impacting red blood cell size.
Chronic alcohol abuse frequently causes macrocytosis, even without liver disease or overt vitamin deficiencies. Alcohol has a direct toxic effect on bone marrow, interfering with red blood cell development and leading to larger cells. This effect is often compounded by poor nutritional intake and malabsorption of B12 and folate common in individuals with alcohol use disorder. Macrocytosis associated with alcohol typically reverses within a few months of abstinence.
Hypothyroidism, where the thyroid gland does not produce enough hormones, can also be associated with macrocytosis. Thyroid hormones play a role in red blood cell production; their deficiency can affect bone marrow activity. While anemia in hypothyroidism is often normocytic, macrocytosis can occur, sometimes due to direct hormone deficiency or indirectly through impaired B12 and folate absorption.
Medications can also induce macrocytosis by interfering with DNA synthesis or bone marrow function. Examples include chemotherapy drugs like hydroxyurea, some anticonvulsants, and antiviral medications. Primary bone marrow disorders, such as Myelodysplastic Syndromes (MDS) or aplastic anemia, involve abnormal blood cell production, resulting in enlarged red blood cells. Reticulocytosis, an increased number of immature red blood cells (reticulocytes) in the bloodstream, can elevate the MCV. Reticulocytes are naturally larger than mature red blood cells and are produced in response to significant blood loss or hemolysis (red blood cell destruction).
Diagnosis and Management
Diagnosing the underlying cause of large red blood cells involves a systematic approach. An elevated MCV from a Complete Blood Count (CBC) serves as a starting point. To pinpoint the reason, additional diagnostic tests are often ordered. These include specific blood tests to measure vitamin B12 and folate levels.
Further blood tests may involve liver and thyroid function tests, and tests for specific antibodies, such as those associated with pernicious anemia. If a primary bone marrow disorder is suspected, a bone marrow biopsy may be necessary to examine the bone marrow. Identifying the specific cause is important because effective management depends on addressing the underlying condition. A healthcare professional interprets all test results within a person’s overall health and medical history to provide an accurate diagnosis and develop a personalized management plan. Always consult a healthcare provider for health concerns; self-diagnosis or self-treatment is not advisable.