From the Guidelines
Low red blood cell (RBC) count combined with high mean corpuscular volume (MCV) typically indicates macrocytic anemia, which is most commonly caused by vitamin B12 deficiency, folate deficiency, alcoholism, liver disease, hypothyroidism, and certain medications, as supported by the most recent and highest quality study 1.
Causes of Macrocytic Anemia
The causes of macrocytic anemia can be categorized into several groups, including:
- Nutritional deficiencies: vitamin B12 deficiency, folate deficiency
- Alcoholism: direct toxic effects on bone marrow and interference with folate metabolism
- Liver disease: affects red blood cell membrane structure
- Hypothyroidism: slows overall metabolism including blood cell production
- Medications: anticonvulsants (phenytoin, valproic acid), chemotherapy drugs (methotrexate, 5-fluorouracil), and antiretrovirals
- Myelodysplastic syndromes: a group of disorders caused by poorly formed or dysfunctional blood cells
- Certain hereditary conditions: such as Fanconi anemia and telomere disorders
- Pregnancy: increased demand for folate and vitamin B12
Diagnostic Approach
The diagnostic approach to suspected macrocytic anemia includes:
- Complete blood count with peripheral smear
- Vitamin levels: vitamin B12 and folate
- Liver function tests
- Thyroid studies
- Bone marrow biopsy: to assess marrow cellularity, fibrosis, and topography
- Cytogenetics: to identify nonrandom chromosomal abnormalities As noted in 1, the diagnostic criteria aim to distinguish myelodysplastic syndromes from reactive causes of cytopenia and dysplasia as well as from other clonal stem cell disorders.
Treatment
Treatment depends on identifying and addressing the underlying cause, such as:
- Vitamin supplementation for deficiencies
- Alcohol cessation
- Medication adjustments
- Treatment of underlying liver disease or hypothyroidism As stated in 1, any cause of anemia that may be rectified independent of cancer therapy should be treated as indicated.
From the FDA Drug Label
Folic acid acts on megaloblastic bone marrow to produce a normoblastic marrow. In man, an exogenous source of folate is required for nucleoprotein synthesis and the maintenance of normal erythropoiesis Folic acid is a precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias.
The causes of anemia with low red blood cell (RBC) count and high mean corpuscular volume (MCV) include:
- Folic acid deficiency: This can lead to megaloblastic and macrocytic anemias, characterized by large red blood cells and a low RBC count 2, 2.
- Vitamin B12 deficiency: Although not directly stated in the provided text, it is implied that vitamin B12 deficiency can also cause megaloblastic anemia, which is characterized by a low RBC count and high MCV.
From the Research
Causes of Anemia with Low RBC Count and High MCV
The causes of anemia with low red blood cell (RBC) count and high mean corpuscular volume (MCV) can be classified into two main categories: megaloblastic and nonmegaloblastic anemia.
- Megaloblastic anemia is caused by impaired DNA synthesis, leading to the release of megaloblasts, which are large nucleated RBC precursors with chromatin that is not condensed 3.
- Nonmegaloblastic anemia entails normal DNA synthesis and is typically caused by chronic liver dysfunction, hypothyroidism, alcohol use disorder, or myelodysplastic disorders 3, 4.
Megaloblastic Anemia
Megaloblastic anemia is the most common cause of macrocytic anemia, and it is often due to a deficiency in vitamin B12 or folate 5, 6.
- Vitamin B12 deficiency is the most common cause of megaloblastic anemia, although folate deficiency can also contribute 3.
- Lack of vitamin B12 and/or folate can lead to elevated homocysteine levels, which is a key factor responsible for megaloblastic anemia 6.
Nonmegaloblastic Anemia
Nonmegaloblastic anemia can be caused by various diseases, including:
- Myelodysplastic syndrome (MDS) 4
- Liver dysfunction 3, 4
- Alcoholism 3, 4
- Hypothyroidism 3, 4
- Certain drugs 4
- Inherited disorders of DNA synthesis 4
Diagnosis and Treatment
Diagnosis of macrocytic anemia involves classifying the anemia into megaloblastic or nonmegaloblastic, and identifying the underlying cause 4.