HEME 02-05: Macrocytic Anemia (Vitamin B12 and Folate Deficiency)

Question 1

What are the signs and symptoms specific to vitamin B12 deficiency?

Answer 1

• neurologic complications – myelin damage, axonal degeneration, neurotransmitter disruption
• paresthesia
• decreased vibratory sense or gait abnormality

Question 2

What are the labs for vitamin B12 levels? (1)

Answer 2

vitamin B12 levels

• note: deficiency may exist before presence of low serum levels – serum values maintained by B12 tissue store

Question 3

What are the labs for folic acid levels? (2)

Answer 3

• serum folic acid level
• erythrocyte folic acid level – less variable than serum, less susceptible to rapid changes in intake (alcohol/diet)

Question 4

Macrocytic Anemia

CBC Levels

Answer 4

• Hb: decreased
• MCV: increased (> 100 fL)
• reticulocyte count: decreased – destruction of fragile, abnormal megaloblastic erythroid precursor

Question 5

What additional labs can be done if serum vitamin B12 is borderline? (2)

Answer 5

• methylmalonic acid (MMA): elevated in vitamin B12 deficiency
• homocysteine: may be elevated in both vitamin B12 and folate deficiency

Question 6

Macrocytic Anemia

Peripheral Blood Smear (2)

Answer 6

• macrocytosis (RBCs appear larger than normal)
• neutrophils with ≥ 5 lobes (normally ≤ 3 lobes) – due to defective DNA synthesis

Question 7

What are the causes of macrocytic anemia? (3)

Answer 7

• abnormalities in RBC production in bone marrow
• altered RBC membrane composition
• increase in % of reticulocytes (which are larger than mature RBCs)

Question 8

What is megaloblastic macrocytic anemia?

Answer 8

ineffective erythropoiesis

• nuclear maturation impaired – cannot replicate and condense properly
• folic acid and vitamin B12 required for RBC maturation

Question 9

What is non-megaloblastic macrocytic anemia?

Answer 9

larger RBCs (macrocytosis) w/o DNA synthesis impairment

• caused by liver disease, alcoholism, hypothyroidism, myelodysplastic syndrome

Question 10

What is the recommended daily allowance for vitamin B12?

Answer 10

• adults: 2 µg
• pregnant or breastfeeding: 2.6 µg

Question 11

What are the risk factors for vitamin B12 deficiency?

Answer 11

• inadequate intake
• decreased ileal absorption
• decreased intrinsic factor
• medications/drugs

Question 12

What drugs can cause vitamin B12 deficiency?

Answer 12

• H2 receptor antagonists
• PPIs
• metformin
• anticonvulsants (phenobarbital, pregabalin, primidone, topiramate)

Question 13

What is the cut-off for serum B12 deficiency levels?

Answer 13

varies from 150-220 pmol/L

Question 14

Who should have a B12 test done?

Answer 14

clinically symptomatic patients with specific features of B12 deficiency

• for asymptomatic patients with risk factors, consider supplementation in lieu of testing

Question 15

What is the recommended dose for vitamin B12 in symptomatic anemia, neurologic or neuro-psychiatric findings, and pregnancy?

Answer 15

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

Question 16

What is the recommended dose for vitamin B12 in adults with pernicious anemia?

Answer 16

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

Question 17

What is the recommended dose for vitamin B12 in adults with dietary deficiency (vegans, vegetarians, infants exclusively breastfed by B12-deficient mother)?

Answer 17

500-2000 mcg orally once daily

Question 18

Cyanocobalamin (3)

Answer 18

• oral/sublingual tab: 250, 500, 1000, 2500 mcg
• liquid: 200 mg/mL
• injection (IM or SC): 1000 mcg/mL

Question 19

Methylcobalamin (1)

Answer 19

• tab: 1000, 2500, 5000 mcg

Question 20

What are possible adverse reactions of vitamin B12 supplementation?

Answer 20

headache, weakness, hypokalemia

Question 21

What are the minimum daily requirements of folic acid?

Answer 21

• 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

Question 22

What is the average dietary intake of folic acid?

Answer 22

50-2000 mcg of folate per day

• result of food fortification
• deficiency has become quite rare

Question 23

What are the risk factors for folate deficiency? (6)

Answer 23

• 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

Question 24

How can folate deficiency be prevented in pregnancy?

Answer 24

supplement with 400 mcg folic acid via prenatal vitamin to reduce risk of neural tube defects

Question 25

How can folate deficiency be prevented in patients with specific risk factors?

Answer 25

supplementation of 1 mg daily is recommended

Question 26

Folic Acid (2)

Answer 26

tab: 0.4, 1, 5 mg - 1-5 mg PO daily injection (IM/SC): 5 mg/mL - 0.4-1 mg IM/SC daily

Question 27

Describe vitamin B12 levels in pregnancy.

Answer 27

maintained at sufficient levels during pregnancy – does not typically require supplementation - exceptions: strict vegans, some vegetarians, patients with malabsorption (pernicious anemia)

Question 28

Describe folic acid levels in pregnancy.

Answer 28

- 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

Question 29

What is the recommended folic acid supplementation in pregnancy?

Answer 29

- 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

Question 30

How much folate is in prenatal vitamins?

Answer 30

1 mg - more than sufficient to meet increased needs of pregnancy

Question 31

What is anemia in postpartum?

Answer 31

Hb < 100 g/L

Question 32

What contributes to anemia in postpartum? (3)

Answer 32

- antepartum anemia not corrected - blood loss during delivery - breastfeeding