Macrocytic Anemia

Question 1

What is macrocytic anemia?

Answer 1

Aka megaloblastic anemia Large erythrocytes produced via DNA synthesis defect

Question 2

Common cause of macrocytic anemia

Answer 2

nutritional deficiencies in vitB12 and/or folate

Question 3

Risk factors for vitamin B12 deficiency

Answer 3

• Pernicious anemia: defective secretion of IF • PPIs • IBD • Small bowel resection • Strict vegetarian diet (B12 in milk, eggs, etc)

Question 4

Risk factors for folic acid deficiency

Answer 4

• etoh dependence via poor diet • liver Dz via poor hepatic stores • pregnancy via increased folate requirements • hemolytic anemia via increased folate requirements • ESRD via folate removal during hemodialysis • Meds: methotrexate, trimethoprim, phenytoin

Question 5

Macrocytic anemia: expected lab values

Answer 5

MCV: >100 fL

MCHC: normal

Serum Folic Acid: <4 ng/mL

Serum cobalamin: <150pmol/L

Homocysteine: >13 micromol/L

Serum methylmalonic acid: >0.4 micromol/L

Urine methylmalonic acid: >3.6 micromol/mol creatinine

Question 6

Vitamin B12 average daily intake & average storage

Answer 6

Avg US diet 5-30mcg daily & liver storage 3000-5000mcg. We use ~2mcg/day, so takes years to develop deficiency

Question 7

Describe vit B12 absorption

Answer 7

Gastric acid and pancreatic proteases release dietary vitB12 → Free Vit B12 binds w/intrinsic factor (IF) → Vit B12-IF complex absorbed in ileum

Question 8

B12 pharmacodynamics: Name 2 important cellular enzymatic reactions

Answer 8

1) combo w/folate for DNA synthesis 2) methylmalonic acid conversion to succinyl-Coenzyme A (CoA) • DNA synthesis interruption most quickly seen in cells w/rapid turnover

Question 9

Clinical manifestations of VitB12 deficiency

Answer 9

hematologic (anemia, pancytopenia), neurologic (peripheral neuropathy, paresthesias), psychiatric (personality changes, depression, dementia, psychosis)

Question 10

Why is it important to distinguish between FAD and VitB12 deficiency?

Answer 10

Folate supplementation will reverse anemia but will not treat CNS Sx, which may become irreversible if untreated.

Question 11

Folic Acid average daily intake & average storage

Answer 11

Avg US diet 50-500 mcg daily (400 mcg recommended, up to 800 if pregnant) 5-20 mg (liver & other tissues) occurs more quickly than vB12 def

Question 12

Where is FA absorbed?

Answer 12

proximal jejunum

Question 13

Why is FA important?

Answer 13

Essential for DNA synthesis – major impact on cells w/rapid turnover

Question 14

How is Vit B12 deficiency treated?

Answer 14

Cyanocobalamin: PO, IM or deep SQ, Intranasal

Question 15

ADRs of cyanocobalamin

Answer 15

Itching, diarrhea, edema

Question 16

How long does Vit B12 deficiency continue?

Answer 16

Typically lifelong

Question 17

When does VB12D require parenteral supplementation?

Answer 17

in pernicious anemia & severe deficiency +/- neurologic Sx / anemia

Question 18

When does VB12D require PO supplementation?

Answer 18

mild to moderate deficiency

Question 19

Combo multivitamins for VB12D and FAD

Answer 19

avoid

Question 20

How to differentiate between B12 and FAD

Answer 20

Clinically difficult but: Time to develop (B12 takes years) Neuro Sx in B12 (Lab: serum levels before any food or blood products) UptoDate

Question 21

When does FAD require parenteral supplementation?

Answer 21

rarely necessary – FA is well absorbed even in severe malabsorption