Definition
- Macrocytic Anemia: Anemia characterized by macrocytosis (MCV > 100 fL) and reduced hemoglobin levels
Classification
- Megaloblastic Anemia: Due to impaired DNA synthesis, often from folate and/or vitamin B12 deficiencies. Features hypersegmented neutrophils.
- Non-Megaloblastic Anemia: Occurs due to various mechanisms without hypersegmented neutrophils.
Epidemiology
- Prevalence: Affects 2-4% of the population, with 60% having anemia.
- Common Causes: Alcohol use, folate and vitamin B12 deficiencies, medications.
- Demographics: More common in middle-aged women (autoimmune causes) and older patients (hypothyroidism, primary bone marrow disease, and vitamin B12 deficiency).
Etiology
- Megaloblastic:
- Folate deficiency: Poor intake, increased need, malabsorption, certain medications.
- Vitamin B12 deficiency: Poor intake, malabsorption (gastric bypass, certain infections, autoimmune conditions), presence of antagonists (nitrous oxide).
- Non-Megaloblastic:
- Alcohol consumption, hereditary spherocytosis, hypothyroidism, liver disease, and reticulocytosis from hemolysis or pregnancy.
Pathophysiology
- Mechanism: Macrocytic anemia results from large RBCs due to ineffective erythropoiesis caused by folate and vitamin B12 deficiencies, affecting DNA/RNA synthesis.
- Daily Needs: Folate (100-200 µg), Vitamin B12 (1 µg). Absorption rates: Folate (400 µg/day), Vitamin B12 (2-3 µg/day).
Histopathology
- Megaloblastic Anemia: Hypersegmented neutrophils, macro-ovalocytes, anisocytosis, and poikilocytosis.
- Non-Megaloblastic Anemia: Round macrocytes or macro reticulocytes without hypersegmented neutrophils, indicative of underlying conditions.
Clinical Presentation
- Symptoms: Dependent on cause, with common features including mood disturbances, neurologic symptoms (B12 deficiency), and signs of underlying diseases.
- Physical Exam: Nonspecific anemia signs, neurologic deficits, signs of underlying diseases (glossitis, hepatosplenomegaly, jaundice).
Evaluation
- Initial Workup: History, physical exam, PBS, reticulocyte count, serum B12.
- Further Tests: Liver and thyroid function tests, reticulocyte count, RBC folate level, homocysteine, methylmalonic acid (MMA).
Treatment and Management
- Folate Deficiency: Oral folic acid (1-5 mg daily), dietary folate-rich foods.
- Vitamin B12 Deficiency: Oral (1000 µg daily for 1 month, then 125-250 µg daily) or intramuscular B12 (1000 µg weekly for 4 weeks, then monthly).
- Monitoring: Improvement in reticulocytosis within 1-2 weeks, anemia resolution in 4-8 weeks. Neurologic symptoms take longer to resolve.
Prognosis and Complications
- Prognosis: Excellent with early identification and treatment.
- Complications: Chronic vitamin B12 deficiency can lead to permanent neurologic damage (subacute combined neurodegeneration).
Differential Diagnosis
- Folate deficiency anemia
- Anemia due to liver disease
- Hypothyroidism
- Myelodysplastic syndrome
- Alcoholism
Patient Education
- Causes and Symptoms: Nutrient deficiencies, poor absorption, underlying conditions. Symptoms include fatigue, memory disturbances, and tingling sensations.
- Diagnosis and Treatment: Office visit, lab work, addressing underlying cause, and nutrient supplementation.
Key Points
- Early identification and treatment are crucial for excellent prognosis.
- Specialist referral is rarely needed unless resistance to therapy or evidence of myelodysplasia/leukemia.
- Comprehensive team-based interprofessional care improves patient outcomes.
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