From the Guidelines
Macrocytosis and elevated Mean Corpuscular Hemoglobin (MCH) are most commonly caused by vitamin B12 deficiency and folate deficiency, as these conditions impair red blood cell maturation, resulting in larger cells with higher hemoglobin content. The most recent and highest quality study, 1, published in 2020, highlights the importance of vitamin B12 and folate in preventing macrocytic anemia. Other causes of macrocytosis and elevated MCH include alcoholism, liver disease, and certain medications, such as anticonvulsants, chemotherapy agents, and antiretrovirals, as noted in 1 and 1.
When investigating macrocytosis with elevated MCH, clinicians should obtain a complete blood count with peripheral smear, vitamin B12 and folate levels, liver function tests, thyroid studies, and a detailed medication and alcohol history.
- Key diagnostic tests include:
- Vitamin B12 and folate levels to identify deficiencies
- Liver function tests to assess liver disease
- Thyroid studies to evaluate hypothyroidism
- Medication and alcohol history to identify potential causes
- Treatment depends on addressing the underlying cause, such as:
- Vitamin supplementation (B12 1000 mcg daily or folate 1-5 mg daily) for deficiencies
- Alcohol cessation for alcohol-related macrocytosis
- Medication adjustment or discontinuation for medication-induced macrocytosis According to 1, treatment of vitamin B12 deficiency involves hydroxocobalamin 1 mg intramuscularly administered on alternate days until there is no further improvement, then hydroxocobalamin 1 mg intramuscularly administered every 2 months, while folate deficiency is treated with oral folic acid 5 mg daily for a minimum of 4 months.
From the Research
Common Causes of Macrocytosis and Elevated MCH
The common causes of macrocytosis, which is generally defined as a mean corpuscular volume (MCV) greater than 100 fL, and elevated Mean Corpuscular Hemoglobin (MCH) can be attributed to several factors, including:
- Vitamin B12 and folate deficiencies, which are among the most common etiologies 2, 3, 4, 5
- Alcoholism, which can lead to macrocytosis and elevated MCH 2, 5
- Medications, which can cause macrocytosis and affect MCH levels 2, 5
- Liver disease, which can result in mild and uniform macrocytosis 4, 5
- Hypothyroidism, which is a less common cause of macrocytosis and elevated MCH 2, 5
- Primary bone marrow dysplasias, including myelodysplasia and myeloproliferative disorders, which can affect MCH levels 2, 5
Megaloblastic vs Non-Megaloblastic Anemia
Macrocytic anemias can be classified into megaloblastic or non-megaloblastic anemia, with megaloblastic anemia being caused by deficiency or impaired utilization of vitamin B12 and/or folate 3, 5. Non-megaloblastic macrocytic anemia, on the other hand, is caused by various diseases such as myelodysplastic syndrome (MDS), liver dysfunction, alcoholism, hypothyroidism, and certain drugs 5.
Diagnostic Approach
A clinical assessment, together with blood count and blood film results, can ensure a correct interpretation of vitamin B12 and folate levels 6. The peripheral smear can also be helpful in delineating the underlying cause of macrocytosis, with megaloblastic anemia characterized by macro-ovalocytes and hyper-segmented neutrophils 2, 4.