In this article, we will discuss three types of macrocytic anemia: B-12 Deficiency Anemia, Pernicious Anemia, and Folate Deficiency Anemia.
Introduction to Macrocytic Anemia
To determine whether it is microcytic, normocytic, or macrocytic anemia, we look at the mean corpuscular volume (MCV). If the MCV is less than 80, then it is considered microcytic anemia. If it’s between 80-100, then it is normocytic anemia. And if it is more than 100, it is macrocytic anemia.
There are many factors that can lead to the development of macrocytic anemia. Most of them involve GI absorption issues or poor diet. For example, B-12 and folate deficiency can be either due to malabsorption or poor diet. The same can be said about alcohol abuse.
Other causes of macrocytic anemia are drug-induced and liver disease.
Vitamin B-12 Deficiency
Vitamin B-12 is also known as cyanocobalamin. It is an essential vitamin that can be found in high concentrations in fish, milk, and red meat. Individuals on a strict vegan diet are at an increased risk of B-12 deficiency due to the lack of these foods in their diet.
How Vitamin B-12 Deficiency Leads to Anemia?
Vitamin B-12 acts as a co-factor for many of the biological processes, including red blood cell production. The lack of vitamin B-12 impedes this pathway, leading to a decrease in DNA synthesis. This results in a decreased amount of red blood cells, leading to anemia.
Vitamin B-12 is absorbed into the body in the terminal ileum by an intrinsic factor. As such,
bariatric surgery or removal of the ileum will result in a decreased capability to absorb vitamin B-12.
Medications that can lead to vitamin B-12 are metformin, PPI, and H2-blockers.
Patient Presentation and Relevant Lab Values
Early symptom (very non-specific): fatigue and lightheadedness
More severe symptoms: glossitis, disturbed vision, reduced sensation and tingling, pale/jaundice, and neuropsychiatric changes
Below normal labs: RBC, HGB, HCT, vitamin B-12
Above normal labs: MCV, MCH, methylmalonic acid (vitamin B-12 is a co-factor in the pathway to metabolize methylmalonic acid).
Treatment for Vitamin B-12 Deficiency
There are several factors that should be considered prior to the treatment initiation, such as hemoglobin level, neurologic symptoms, patient risk factors, and their ability to absorb vitamin B-12.
If hemoglobin is below 8 (normally 14-17 for males and 12-15 for females), it is considered severe anemia. In severe or symptomatic anemia, it is typically recommended that the patients be treated with parenteral cyanocobalamin.
Mild, asymptomatic, and maintenance cases can be treated with either parenteral cyanocobalamin or oral agents.
Parenteral B-12 is typically initiated 3 times weekly for 1 week, then decrease to once weekly for 4-8 weeks, and then decrease to once a month during the maintenance phase.
Oral B-12 is typically dosed once daily and can be obtained over the counter.
There is a nasal formulation that is available, but it is not commonly used due to the high cost.
Keep in mind that our body stores a very large supply of vitamin B-12 (5-10 years supply), so malabsorption may not show up until much later.
Monitoring
- Lab: CBC and vitamin B-12 level
- Counsel: appropriate needles and injection techniques
- Counsel: potential ADRs, such as headache, infection risk, or asthenia
Pernicious Anemia
Pernicious anemia is an autoimmune disease where intrinsic factor in the gut is targeted by auto-antibodies. Due to the lack of this intrinsic factor, the patient cannot absorb vitamin B-12 from the gut.
Because of this, patients cannot be treated by increasing oral intake of vitamin B-12 and must utilize cyanocobalamin (B-12) injection instead.
Folate Deficiency Anemia
Similarly to vitamin B-12, folate is an important co-factor in the pathway that produces red blood cells. A deficiency of folate leads to a reduction in the number of red blood cells and anemia. Folate is typically found in leafy green vegetables and is absorbed in the jejunum by conjugase enzymes. One of the primary causes of folate deficiency is an insufficient intake of folate stemming from alcoholism and poor diet. Also similarly to vitamin B-12 deficiency, bariatric surgery can lead to malabsorption. Celiac disease can also lead to malabsorption. The most common reason for folate deficiency is pregnancy due the increased utilization.
Folate is very important in pregnancy because it plays a crucial role in fetal development. Insufficient folate can lead to neural tube defects. It is generally recommended that pregnant individuals consume 400-1000 mcg of folate by mouth once daily.
Patient Presentation and Relevant Lab Values
Early symptoms are very non-specific. These include fatigue and light-headedness.
Advanced symptoms include oral ulcers, neuropsychiatric changes, and neural tube defects in the fetus.
Below normal lab values: RBC, HGB, HCT, Vitamin B-12 (or WNL), Folic acid
Above normal lab values: MCV and MCH
Folate deficiency does not affect the concentration of methylmalonic acid. As such, the value for methylmalonic acid should be within the normal limit (WNL). With folate deficiency, you can see low B-12. This is because B-12 plays a role in the folate pathway as well.
The main lab differences between vitamin B-12 and folate deficiency are methylmalonic acid (high in vitamin B-12 and normal in folate) and folate (normal in vitamin B-12 and low in folate).
Folate Deficiency Treatment
Unlike vitamin B-12, we don’t have as large of storage for folate. Typically, folate can be depleted over the course of weeks to months, and the storage is depleted at a quicker pace than vitamin B-12 due to a higher demand for cell division.
The first step is to replete the folate storage. This is done through oral folic acid 1-5mg once daily. There is an IV formulation available for patients who cannot tolerate oral formulation. Please note that this is not an appropriate dose for pregnancy (400-1000mg).
The second step is to maintain folate storage is needed. This is done with oral folic acid 400mcg once daily.
Follow-up and counseling are similar to those for vitamin B-12 deficiency.