Macrocytic Anemia | Megaloblastic vs Non-Megaloblastic | Approach & Causes

Macrocytic Anemia

In this lesson, we will discuss macrocytic anemia, its definition, causes and approach to diagnosis.

Definition of Macrocytic Anemia

• A low hemoglobin level is considered anemia.

• Hemoglobin less than 13g/dL in men, less than 12g/dL in non-pregnant women and less than 11g/dL in pregnant women is considered anemia.

• MCV (mean corpuscular volume) tells us the average size of cells.

• MCV greater than 100 indicates macrocytic anemia.

Approach to Diagnosis

• Blood smear looking at PMNs or polymorphonuclear leukocytes can help diagnose macrocytic anemia.

• If a neutrophil has more than five lobes on a blood smear, it is megaloblastic. Less than five lobes indicate non-megaloblastic.

• Megaloblastic means there are hypersegmented neutrophils indicating impaired DNA synthesis.

• Non-megaloblastic means there is no issue with DNA synthesis.

Causes of Macrocytic Anemia

Megaloblastic Anemia

This section discusses the causes of megaloblastic anemia which include deficiencies and other factors that affect DNA synthesis.

Deficiencies

• Folate deficiency can cause macrocytic megaloblastic anemia.

• Sources of folate come from leafy greens and fortified grains.

• Reduced dietary intake, compromised absorption, impaired metabolism and increased demand during pregnancy are some causes of folate deficiency.

Other Factors Affecting DNA Synthesis

• Vitamin B12 deficiency can also cause megaloblastic anemia due to impaired DNA synthesis.

• Pernicious anemia is a type of vitamin B12 deficiency caused by autoimmune destruction of parietal cells in the stomach.

• Other causes of megaloblastic anemia include drugs that interfere with DNA synthesis such as methotrexate and hydroxyurea.

Non-Megaloblastic Anemia

This section discusses the causes of non-megaloblastic anemia which include liver disease, alcoholism, hypothyroidism and certain medications.

Causes

• Liver disease can cause non-megaloblastic anemia due to impaired production of red blood cells.

• Alcoholism can lead to non-megaloblastic anemia due to poor nutrition and impaired absorption of nutrients.

• Hypothyroidism can also cause non-megaloblastic anemia due to decreased erythropoietin production.

• Certain medications such as zidovudine and chemotherapeutic agents can also cause non-megaloblastic anemia.

Vitamin B12 and Folate Deficiency

This section discusses the causes of vitamin B12 deficiency, how to distinguish between folate and vitamin B12 deficiencies, and the neurological symptoms associated with vitamin B12 deficiency.

Causes of Vitamin B12 Deficiency

• Vitamin B12 deficiency can be caused by reduced dietary intake or compromised absorption.

• Reduced dietary intake is common in vegans who do not supplement their diet appropriately.

• Compromised absorption can be seen in pernicious anemia where the body is unable to absorb vitamin B12 properly.

Distinguishing Between Folate and Vitamin B12 Deficiencies

• Both folate and vitamin B12 deficiencies cause macrocytic megaloblastic anemia.

• To distinguish between the two, look at folate levels and vitamin B12 levels.

• If folate levels are very low but normal for vitamin B12, it indicates a folate deficiency.

• If vitamin B12 levels are very low but normal for folate, it indicates a vitamin B12 deficiency.

• If both levels are equivocal, look at methylmalonic acid level:

• High methylmalonic acid level indicates a vitamin B12 deficiency.

• Normal methylmalonic acid level indicates a folate deficiency.

Neurological Symptoms Associated with Vitamin B12 Deficiency

• Vitamin B12 deficiency can lead to neurological symptoms such as paresthesias (tingling sensation), issues with proprioception (awareness of body position), and two-point discrimination.

Causes of Macrocytic Megaloblastic Anemia

This section discusses the causes of macrocytic megaloblastic anemia and how to distinguish between vitamin B12 and folate deficiencies.

Causes of Macrocytic Megaloblastic Anemia

• Vitamin B12 and folate deficiencies are not the only causes of macrocytic megaloblastic anemia.

• The D's mnemonic can help remember other causes:

• DNA affecting drugs such as methotrexate, azathioprine, sulfonamides, antivirals, antiepileptics, chemotherapies, pyrimethamine, sulfasalazine, and triamterene.

Distinguishing Between Vitamin B12 and Folate Deficiencies

• To distinguish between vitamin B12 and folate deficiencies causing macrocytic megaloblastic anemia:

• Look at neutrophils on a blood smear. If they're hyper-segmented (more than five or six lobes), it indicates megaloblastic anemia.

• Look at methylmalonic acid level:

• High methylmalonic acid level indicates a vitamin B12 deficiency.

• Normal methylmalonic acid level indicates a folate deficiency.

Causes of Macrocytic Non-Megaloblastic Anemia

This section discusses the causes of macrocytic non-megaloblastic anemia.

Causes of Macrocytic Non-Megaloblastic Anemia

• Endocrine causes such as hypothyroidism can cause macrocytic non-megaloblastic anemia.

• Genetic causes such as hereditary spherocytosis and Down syndrome can also cause this type of anemia.

• Reactive causes include reticulocytosis.

Macrocytic Non-Megaloblastic Anemia

This section discusses the causes of macrocytic non-megaloblastic anemia.

Causes of Macrocytic Non-Megaloblastic Anemia

• Reactive causes and some other causes of macrocytic non-megaloblastic anemia include pregnancy, which is related to reticulocytosis.

• Liver disease and alcoholism are two major causes of macrocytic non-megaloblastic anemia. Hypothyroidism is another cause.

• Other possible causes include medications, such as chemotherapy drugs, and certain genetic disorders.

Conclusion

• In conclusion, this lesson provided an overview of macrocytic non-megaloblastic anemia and its various causes.