What type of anemia is deficient in folate (Vitamin B9) and Vitamin B12?

Megaloblastic Anemia is Caused by Deficiencies in Folate and Vitamin B12

Deficiencies in both folate (vitamin B9) and vitamin B12 cause megaloblastic anemia, characterized by macrocytic red blood cells and ineffective erythropoiesis. 1, 2

Pathophysiology and Classification

• Megaloblastic anemia is a macrocytic anemia (MCV > 100 fL) resulting from impaired DNA synthesis and ineffective red blood cell production 1
• Both vitamin B12 and folate are essential for DNA synthesis, and deficiency in either or both leads to megaloblastic changes in the bone marrow 2
• Megaloblastic anemia is characterized by:
  • Macrocytic (large) red blood cells 1
  • Ineffective erythropoiesis in the bone marrow 3
  • Pancytopenia (anemia, leukopenia, thrombocytopenia) 1

Clinical Manifestations

• Common symptoms include fatigue, weakness, pallor, glossitis, and angular stomatitis 1
• Neurological symptoms (including sensory disturbances, motor weakness, and gait abnormalities) occur in vitamin B12 deficiency but not in isolated folate deficiency 1, 2
• Both deficiencies can cause:
  • Megaloblastic changes in the bone marrow 3
  • Glossitis and oral ulcers 1
  • Neuropsychiatric manifestations (depression, irritability, cognitive impairment) 1

Diagnostic Approach

• Diagnosis begins with identification of macrocytosis (MCV > 100 fL) on complete blood count 1
• Laboratory evaluation should include:
  • Serum vitamin B12 levels 1
  • Serum folate and/or red blood cell folate levels 1
  • Plasma homocysteine (elevated in both deficiencies) 1
• Important warning: Always check vitamin B12 levels before treating folate deficiency, as folate supplementation can mask B12 deficiency while allowing neurological damage to progress 1, 4

Causes of Deficiency

Vitamin B12 Deficiency

• Pernicious anemia (autoimmune destruction of intrinsic factor) 2
• Gastric surgery or disorders affecting the stomach 2
• Intestinal malabsorption disorders 1
• Strict vegetarian/vegan diet without supplementation 2
• Medications (e.g., metformin, proton pump inhibitors) 1

Folate Deficiency

• Inadequate dietary intake (less common since food fortification) 1
• Increased demand (pregnancy, hemolytic anemia) 1
• Malabsorption syndromes 1
• Medications (anticonvulsants, methotrexate, sulfasalazine) 1
• Alcoholism 1

Treatment Approach

For Vitamin B12 Deficiency

• Always treat B12 deficiency before initiating folate supplementation 1, 4
• For patients with neurological involvement:
  • Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then 1 mg every 2 months 1
  • Urgent neurological and hematological consultation 1
• For patients without neurological involvement:
  • Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, followed by maintenance with 1 mg every 2-3 months lifelong 1
• Oral vitamin B12 supplementation (2,000 mcg daily) may be effective in some cases 1

For Folate Deficiency

• After excluding vitamin B12 deficiency, treat with:
  • Oral folic acid 5 mg daily for a minimum of 4 months 1
• Investigate potential causes of folate deficiency, including medication effects and malabsorption 1

Important Clinical Considerations

• Folate supplementation can mask the hematologic manifestations of B12 deficiency while allowing neurological damage to progress - this is why B12 deficiency must be ruled out before treating with folate 1, 4
• The prevalence of folate deficiency has decreased significantly in countries with mandatory food fortification programs 1
• Both deficiencies often coexist, especially in elderly patients and those with malabsorption disorders 1
• Elevated MCV and MCH may be present before anemia develops, suggesting that monitoring these parameters can help with early detection 5
• Response to appropriate vitamin replacement therapy should be evident within days to weeks, with reticulocytosis occurring first, followed by normalization of hemoglobin levels 6