14 Hypoprolferative anemias

Question 0

Treatment for Severe Aplastic Anemias

Answer 0

• Matched Sibling BMT
• Immunosuppression for acquired- Alemtuzumab(Antithymocyteglobulin) / Cyclophosphamide
• Unrelated BMT
• Haplo/cord BMT/
• Eltrombopag (thrombopoieten analogue)

Question 1

Camitta criteria for Severe Aplastic Anemia

Answer 1

2/3 in peripheral blood:
PMN < 20K/ul
Plaetelets<20k/ul

65% hematopoietic left in BM

Question 2

Acquired aplastic anemia

Answer 2

• Normocytic normochromatic pan-anemia
• Hypocellular bone marrow 2/2 auttoreactive T cells
  
  • Inciting event usually infectious or drug related.

Question 3

Fanconi Anemia

Answer 3

Pancytopenia related to DNA repair enzyme defects
1/3 of patents are normal, 2/3 have bone changes, extra thumb, cafe au’ lait spots, small head, and are short.

RULE OUT FANCONI ANEMIA BEFORE CHEMO

DEB test oxidatively stresses cells to check for fanconi’s
CAN BMT These with low chemo

Question 4

Dyskeratosis congenita

Answer 4

TERT deficiency- Aplastic anemia 2/2 short telomeres
Also get Pulmonary fibrosis and cirrhosis

Lukoplakia, dystrophic fingernails and toenails, gray hair, Lacy pigmentation of skin, leukoplakia

Question 5

Pancytopenia differential

Answer 5

Stem cell disorders like PNH
Ineffective Hematopoeisis - MDS and Megaloblastic anemia
Marrow infiltration- neoplastic or fibrosis
Splenic sequestration
Drugs- Immunosuppression/chemo

Question 6

Megaloblastic anemias

Answer 6

Macrocytic anemia with oval macrocytes, teardrops, Hypersegmented neutrophils, anisopoikilocytosis.
BM: Hypercellularity with nuclear cytoplasmic dyssynchrony.

Problems with nuclear maturation due to Folate deficiency or B12 deficiency. Both implicated in maintainance of TH4-folate levels (needed for DNA synthesis)

Question 7

B12 deficiency anemia

Answer 7

Megaloblastic anemia with increased Methylmalonic acid levels and low reticulocyte count

Usually due to anti Parietal cell autoimmunity.
B12+haptocordin in digestion –> IF in dduodenum –>Cubulin in enterocytes –>plasma transcobalamin

Causes dorsolateral demyelination
TREAT WITH ORAL OR IV B12- NOT FOLATE!!!

Question 8

Folate deficiency anemia

Answer 8

Megaloblastic anemia 2/2 decr uptake, increased demand (growth/prgnancy), defective absorption, or chemo

Insidious onset, fatigue, malaise
Causes spina bifida oculta and anencephaly in fetuses

FOLATE SUPPLEMENT TX

Question 9

Iron deficiency anemia

Answer 9

Microcytic hypochromic anemia caused by low iron- blood loss, low intake, malabsorption

S/S- immune deficiency, impaired cognition and growth

Low serum ferritin (<12ug/L is diagnostic)
Low serum iron
Causes increased TIBC(total iron binding capacity opposite of ferritin)

Question 10

Iron uptake in duodenum

Answer 10

Must be reduced to FE2+ by duodenal cytochrome C
Dication metal transporter 1 (DMT1) uptake
Bound by Mucosal ferritin
Ferroportin transporter brings into interstitium depending on HEPCIDIN
Oxidized by hephaestin to 3+ for transfer to transferrin

Question 11

Sideroblast

Answer 11

Erythroid cell with Iron deposit (usually one small deposit for heme synthesis- can get many deposits in Myelodisplastic

Question 12

Anemia of chronic disease

Answer 12

Normocytic or microcyitic, usually normochromic Anemia

• Decreased erythropoeisis 2/2 chronic inflammation
• chronic infection, immune dysfunction, neoplastic disorders
• ^HEPCIDIN DECREASES FEROPORTIN EXPORTER and less FE released into plasma
• EPO Suppression

*Low serum iron, LOW TIBC, INCREASED FERRITIN, INCREASED BM IRON STORES

No sideroblasts, no polychromasia, fever reticulocytes

TX-> EPO and treat chronic disease

Question 13

Pure Red Cell Aplasia

Answer 13

No erythroid precursors.

Associated with: Thymomas, Thymic hyperplasia, Autoimmune disorders, Drugs, Large Granular Lymphocytic Leukemia

Question 14

Myelophthisic Anemia

Answer 14

*Teardrop cells

• Bonemarrow displacement by metastatic carcinoma
• Leukperythrblastic reaction- (immature erythroids and myeloids in periphery)