2013-10-16 Anemia II (Micro- and Normocytic)

Question 0

Best test to determine Fe-deficiency?

Answer 0

ferritin (the bus)

Question 1

TIBC

Answer 1

measures amount of transferrin (blood borne Fe carrier that only holds 2 Fe molecules)

Question 2

hepcidin

Answer 2

controls Fe absorption in the duodenum; decr in anemia of chronic dz

Question 3

iron stores in the body

Answer 3

Hgb (MOST)
Myoglobin
ferritin (“the bus;”in M0s of spleen, liever, marrow)
transferrin (“the car;” TIBC; in circulation)

Question 4

transferrin saturation lab interpretation

Answer 4

transferrin sat INCR in IRON OVERLOAD (e.g. mhemochromatosis)
transferrin sat DECR in decr supply of Fe from M0s and other stores (e.g. as in anemia of chronic dz)

Question 5

1. Iron def anemia:
   - s/sx
   - smear findings
   - lab findings

Answer 5

s: koilonychia, glossitis, angular cheilosis
sx: pica, RLS
smear: microcytic, hypochromic, anisocytotic, poikilocytotic (weird shapes) RBCs
labs: LOW FERRITIN, low serum Fe, low transferrin sat, incr TIBC
low MCV (microcytes)
low MCH/MCHC (hypochromic)
incr RDW (anisocytosis)

Question 6

2. sideroblastic anemia
   - cause
   - s/sx
   - smear
   - lab findings
   - tx

Answer 6

• cause: decr heme synth -> excess free Fe;
• -1°: ALA synthase def; MDS
• -2°: Pb poison; B6/Cu def; isoniazid/chloramphenicol; EtOH/Zn/
• s/sx of lead poisoning: Pb-line on gums, lead colic (autonomic dysfxn), insomnia, irritability, psychosis
• smear: ringed sideroblasts (excess Fe)
• lab: high serum Fe, ferritin, transferrin SAT; TIBC (transferrin conc) is LOW/nl; high blood lead level
• tx: ∆ meds/toxins/EtOH; PRBCs; Fe-chelation

Question 7

3. Thalassemias
   - genetics
   - presentation
   - dx
   - complications

Answer 7

GENETICS
-both: autosomal recessive
ALPHA:
-decr alpha; excess Beta
-dx w/ DNA anaysis b/c electrophoresis nl

BETA

• target cells
• dx w/ hgb electrophoresis

COMPLICATIONS
-both: Fe overload

Question 8

4. anemia of chronic dz
   - incidence
   - smear
   - pathophys

Answer 8

INCIDENCE
—most common normocytic anemia w/ low retic count
—2nd most common anemia overall (after IDA)

SMEAR
—usu normocytic and normchromic (though both can be low)

PATHOPHYS

• chronic disease (infx, inflamm, malig)
• > > cytokines
• > > increases hepcidin
• > > > > > increases storing in M0s (ferritin)
• > > > > > decreases epo, duodenal Fe uptake, Fe release from stores

Question 9

5. aplastic anemia

Answer 9

• normocytic w/ low retic count (less common than anemia of chronic dz)
• pancytopenia (leukopenia and thrombocytopenia bigger concerns!)
• 1°: idiopathic
• 2°: meds (chemo, chloramphenicol, AEDs); toxin (benzene); radiation; viral (Parvovirus B19, EBV)

Question 10

6. anemia of chronic kidney diease

Answer 10

another normocytic w/ low retic
—low epo, blood loss (repeated phleb, machine, uremic plt dsfx)
—shortened RBC life 2° to uremia

Question 11

endocrinopathies that cause normocytic normochromic anemia

Answer 11

• hypothyr
• hypoparathyr
• panhypopituitarism
• low Test (2° to prostate cancer tx)

Question 12

intravascular vs. extravascular hemolysis: s/sx/labs

Answer 12

INTRAVASCULAR

• high LDH, low haptoglobin
• hemoglobenemia (red plasma)
• hemoglobulinuria (red pee)
• JAUNDICE
• schistocytes

EXTRAVASCULAR

• still JAUNDICE
• mostly in spleen so no hgb-enmia/uria

Question 13

7. immune hemolytic anemias

Answer 13

Normocytic HYPERchromic –> immune hemolytic anemias

• dx: nl MCV, high RPI, positive COOMBS Test
• tx: fix underlying cause, steroids, immunosupp, rituximab, splenectomy (last resort)

Question 14

8. MAHA - Microangiopathic Hemolytic Anemia
   - causes
   - s/sx
   - labs/smear

Answer 14

Normocytic HYPERchromic –> immune hemolytic anemias

• causes: TTP (ADAMTS13 mutation -> long, potent vWFs), HUS (shiga toxin), HIV, heart valves
• s/sx: DIC, malfunctioning heart valve
• labs/smear: schistocytosis, thrombocytopenia

Question 15

9. PNH
   - name
   - pathophys
   - s/sx
   - labs/smear
   - tx

Answer 15

Normocytic HYPERchromic –> Membranopathies -> PNH

• NAME:paroxysmal nocturnal hemoglobulinuria
• defect in GPI glycolipid on cell surface makes RBCs susceptible to MAC attack
• dark urine in a.m., incr thrombosis
• labs: flow shows decr CD59 which needs GPI to anchor
• tx: Fe, Folate, eculizumab (C5 inhib), stem cell transplant

Question 16

10. Hereditary Spherocytosis
    - pathophys
    - labs/smear
    - tx

Answer 16

Normocytic hyperchromic –> membranopathies –> herid. spher.

• abnl shape b/c of autosomal dominant mutation in various prots that anchor membrane to cytoskel
• hyperchromic b/c cells shrinking in spleen where eventually removed
• smear shows no donut hole, labs: low h/h, lowish/nl MCV
• tx: splenectomy

Question 17

11. G6PD
    - pathophys
    - inheritance pattern
    - tx

Answer 17

Normocytic, hyperchromic –> G6PD

• enzyme needed to recycle glutathione which protects RBCs from oxidative damage
• x-linked
• avoid exposures

Question 18

12. some drugs that cause hemolytic anemia

Answer 18

normocytic hyperchromic anemia –> hemolytic –> drug-induced
1. penicillin (hapten; ab directed toward Abx-membrane complex)
2. quinidine (deposition of complement via a drug-prot-Ab cmplx)
3. methyldopa (truly autoimmune; role of drug unknown)
BOOK PG. 85

Question 19

13. some infxs that cause haemolytic anemia

Answer 19

normocytic hyperchromic–> hemolytic –> infectious
—malaria
—babesiosis (Ioxodes ticks on Cape Cod)

Question 20

14. Sickle Cell

Answer 20

normocytic hyperchromic–> haemolytic –> SCD
—makes HbS b/o glu –> val ∆
—HbS polymerizes

HEMOLYSIS: jaundice, anemia, pigment gallstones
INFXS: encapsulated organs, bones
VASO-OCCLUSIVE: pain, CP, priapism, avacular hip necrosis, CVAs, retinopathy
APLASTIC EPISODES: with Parvovirus B-19 infection

Question 21

Work-up for a hemolytic anemia

Answer 21

establish hemolysis: hi retic,; hi LDH/bili, lo hapto
check smear:
—spherocytes? = extravasc
—schistocytes? = intravasc
Coombs Test: auto-immune?