2013-10-23 Anemia III (Macrocytic); MDS

Question 0

causes of b12 deficiency

Answer 0

MOUTH: nutrition (vegan, alcoholic) ?low R-binder?
STOMACH: pernicious anemia Abs?
PROX BOWEL: pancreatitis (cleaves off R-binder), bact overgrowth, sprue, parasites
DISTAL BOWEL: Chron’s, resection

MEDS: neomycin, metformin, omeprazole

Question 1

1. B12 deficiency
   —Time course
   —Causes
   —Pathophys

Answer 1

macrocytic –> megaloblastic –> b12 def
—takes a long time to happen
—CAUSES: #1 = pernicious anemia; dietary (only available in animal products)
—PATHOPHYS: diet -> methyl folate -> THF ->-> dUMP->dTMP; you still have uracil, so RNA builds up -> more prot -> big cells that can’t divide
—S/SX: developmental issues, anemia, pancytopenia, demyelination (imbalance/gait, parasthesias, decr vibe sense, cognitive deficits)
—PATH: macrocytosis w/ ovalocytes; hyperseg PMNs
—DX: [1] CBCs and/or neuro s/sx (not all B12 def pts get anemic), [2] measure b12 & folate, [3] if borderline B12 level, get homocysteine & methylmalonic acid, [4] Abs to I.F./parietal cells?
—TX: high dose B12 I.M.

Question 2

2. Folate Deficiency
   - diet source?
   - folate role?
   - s/sx?
   - tx?

Answer 2

SOURCE: leafy greens
ROLE: cofactor for thymidylate synthase (needed for DNA synth)
S/SX: same heme sx as B12 but NO NEURO SX
TX: Never tx w/ empiric folate alone, always give w/ B12
—If you have co-morbid B12 def can get subacute combined degeneration of spinal cord

Question 3

causes of folate deficiency

Answer 3

MOUTH: decr intake (overcooked, older folks, EtOH)
BOWEL: sprue, IBD, infiltrative bone dz, short bowel
DRUGS: MTX, trimethoprim, EtOH, phenytoin
OTHER: incr demand (preg, lactation, chronic hemolysis, exfolitative dermatitis)

Question 4

interpretation of Methylmalonic acid and homocysteine tests

—Why?

Answer 4

HIGH MMA and Homo = B12
nl MMA, HIGH homo = folate
—both needed for Succinyl-CoA synth from MMA-CoA; deficiencies cause back-up

Question 5

Macrocytic Anemia Work-Up

Answer 5

1. Retic count + smear
2. B12, folate, TSH, LFTs
3. EtOH hx?
4. Diet?
5. Check pt’s med list

Question 6

B12 is called

Answer 6

cobalamin

Question 7

Which vitamin is folate?

Answer 7

B9

Question 8

MDS Romanian Mnemonic

Answer 8

Crazy, packed parking lot of junk cars = hypercellular dysplastic BM
—empty streets = periph pancytopenia/bicytopenia

Question 9

3. MDS-related anemia
—causes
—path
—presentation
—TX

Answer 9

—causes: s/p chemo or rad; common in elderly
—PATH: dyserythopoietic RBCs; micromegakaryocytes, pseudo-Pelger-Huët PMNs (hyposegmented)
—PRESENT: normocytic anemia, bruise/bleed, infections
—TX: depends on severity; GFs, transfuse (may then need to chelate b/c iron overload), 5-azacytadine, lenalinomide, BM transplant

Question 10

4. Macrocytosis and Alcoholism
   - Amount needed
   - Mechanism
   - Path

Answer 10

EtOH NEEDED: >80g/day (wine bottle ~80g)
MECH: [1] malnutrition (B9/B12 def), [2] liver dz -> lipid probs -> incr cell size/mcv, [3] acetaldehyde
PATH: acanthocytes, target cells, macrovalocytes, hyperseg PMNs

Question 11

Drugs that cause Macrocytic Anemia

Answer 11

Anti-Cancer: hydroxyurea, MTX, capscitabine, cladribine, imatinib, sutinib,

Psych/Neuro: valproate, phenytoin

ID: zidovudine, bactrim (trimethoprim)

Others: Omeprazole, metformin