HEME 02-05: Macrocytic Anemia (Vitamin B12 and Folate Deficiency) Flashcards
What are the signs and symptoms specific to vitamin B12 deficiency?
- neurologic complications – myelin damage, axonal degeneration, neurotransmitter disruption
- paresthesia
- decreased vibratory sense or gait abnormality
What are the labs for vitamin B12 levels? (1)
vitamin B12 levels
- note: deficiency may exist before presence of low serum levels – serum values maintained by B12 tissue store
What are the labs for folic acid levels? (2)
- serum folic acid level
- erythrocyte folic acid level – less variable than serum, less susceptible to rapid changes in intake (alcohol/diet)
Macrocytic Anemia
CBC Levels
- Hb: decreased
- MCV: increased (> 100 fL)
- reticulocyte count: decreased – destruction of fragile, abnormal megaloblastic erythroid precursor
What additional labs can be done if serum vitamin B12 is borderline? (2)
- methylmalonic acid (MMA): elevated in vitamin B12 deficiency
- homocysteine: may be elevated in both vitamin B12 and folate deficiency
Macrocytic Anemia
Peripheral Blood Smear (2)
- macrocytosis (RBCs appear larger than normal)
- neutrophils with ≥ 5 lobes (normally ≤ 3 lobes) – due to defective DNA synthesis
What are the causes of macrocytic anemia? (3)
- abnormalities in RBC production in bone marrow
- altered RBC membrane composition
- increase in % of reticulocytes (which are larger than mature RBCs)
What is megaloblastic macrocytic anemia?
ineffective erythropoiesis
- nuclear maturation impaired – cannot replicate and condense properly
- folic acid and vitamin B12 required for RBC maturation
What is non-megaloblastic macrocytic anemia?
larger RBCs (macrocytosis) w/o DNA synthesis impairment
- caused by liver disease, alcoholism, hypothyroidism, myelodysplastic syndrome
What is the recommended daily allowance for vitamin B12?
- adults: 2 µg
- pregnant or breastfeeding: 2.6 µg
What are the risk factors for vitamin B12 deficiency?
- inadequate intake
- decreased ileal absorption
- decreased intrinsic factor
- medications/drugs
What drugs can cause vitamin B12 deficiency?
- H2 receptor antagonists
- PPIs
- metformin
- anticonvulsants (phenobarbital, pregabalin, primidone, topiramate)
What is the cut-off for serum B12 deficiency levels?
varies from 150-220 pmol/L
Who should have a B12 test done?
clinically symptomatic patients with specific features of B12 deficiency
- for asymptomatic patients with risk factors, consider supplementation in lieu of testing
What is the recommended dose for vitamin B12 in symptomatic anemia, neurologic or neuro-psychiatric findings, and pregnancy?
1000 mcg IM/SC every other day initially for approximately 2 weeks, followed by once monthly
- when initial deficiency has been corrected, oral trial is reasonable based on patient preference and adequate B12 levels
What is the recommended dose for vitamin B12 in adults with pernicious anemia?
1000 mcg (1mg) IM/SC once per week for 4 weeks, followed by 1000 mcg once per month
- treat for life
- when all things normalized and no symptoms: 1000-2000 mcg (1-2 mg) PO daily x lifelong
What is the recommended dose for vitamin B12 in adults with dietary deficiency (vegans, vegetarians, infants exclusively breastfed by B12-deficient mother)?
500-2000 mcg orally once daily
Cyanocobalamin (3)
- oral/sublingual tab: 250, 500, 1000, 2500 mcg
- liquid: 200 mg/mL
- injection (IM or SC): 1000 mcg/mL
Methylcobalamin (1)
- tab: 1000, 2500, 5000 mcg
What are possible adverse reactions of vitamin B12 supplementation?
headache, weakness, hypokalemia
What are the minimum daily requirements of folic acid?
- general: 50-100 µg
- pregnant: 600 µg
- lactating: 500 µg
- increased in conditions with high metabolic rate and cellular division rate – pregnancy, infancy, infection, malignancies, hemolytic anemia
What is the average dietary intake of folic acid?
50-2000 mcg of folate per day
- result of food fortification
- deficiency has become quite rare
What are the risk factors for folate deficiency? (6)
- alcoholic
- pregnancy
- conditions with rapid cellular turnover
- diet lacking in folate (weight-loss)
- diseases that impair absorption from the small intestine
- drugs that alter folate metabolism
note: few patients have inborn errors of folate metabolism
How can folate deficiency be prevented in pregnancy?
supplement with 400 mcg folic acid via prenatal vitamin to reduce risk of neural tube defects
How can folate deficiency be prevented in patients with specific risk factors?
supplementation of 1 mg daily is recommended
Folic Acid (2)
tab: 0.4, 1, 5 mg
- 1-5 mg PO daily
injection (IM/SC): 5 mg/mL
- 0.4-1 mg IM/SC daily
Describe vitamin B12 levels in pregnancy.
maintained at sufficient levels during pregnancy – does not typically require supplementation
- exceptions: strict vegans, some vegetarians, patients with malabsorption (pernicious anemia)
Describe folic acid levels in pregnancy.
- prevalence of deficiency in pregnancy varies – higher in economically deprived regions
- poor nutrition, intestinal malabsorption, and increased requirements for fetal growth may contribute to folate deficiency
What is the recommended folic acid supplementation in pregnancy?
- WHO: 400 mcg/day from early pregnancy to 3 months postpartum
- US Public Health Service and CDC: 400 mcg for all women of childbearing age (15-45 years) to prevent spina bifida and anencephaly
How much folate is in prenatal vitamins?
1 mg
- more than sufficient to meet increased needs of pregnancy
What is anemia in postpartum?
Hb < 100 g/L
What contributes to anemia in postpartum? (3)
- antepartum anemia not corrected
- blood loss during delivery
- breastfeeding
