2 - Stem Cell Hematopoiesis and Bone Marrow Failure

Question 1

sites of early hematopoiesis

Answer 1

yolk sac blood islands (16 d)
aortogonadomesonephros (20-30 d)
liver (6 w)
bone marrow (5 mo - postnatal)
thymus (T cell development)

Question 2

lymphoid derived cells

Answer 2

T, B, NK, dendritic

Question 3

myeloid derived cells

Answer 3

RBCs, megakaryocytes/platelets, monocytes/macrophages, granulocytes

Question 4

3 important characteristics of hematopoietic stem cells

Answer 4

multipotent
self renewing
quiescent (only divide when needed)

Question 5

what class of signaling molecules are responsible for directing stem cell trafficking?

Answer 5

cytokines

Question 6

severe aplastic anemia (SAA) definition

Answer 6

bone marrow hypocellularity (<20k)

Question 7

5 categories of causes for pancytopenia

Answer 7

HSC injury
clonal hematopoietic cell mutation
myelophthisis (BM infiltration)
defective maturation
enhanced peripheral destruction

Question 8

causes of bone marrow failure

Answer 8

congenital (Fanconi anemia, dyskeratosis congenita, Shwachman Diamond syndrome, Diamond-Blackfan anemia, congenital amegakaryocytic thromboctyopenia)
acquired (toxic, drugs, viral infxn)
idiopathic (thought to be immune mediated)

Question 9

Fanconi anemia

Answer 9

AR inheritance, variable phenotype
DNA repair disorder

cafe au lait spots, microophthalmia, abnormal thumbs, predisposed to AML/MDS and other cancers

Question 10

Diamond Blackfan anemia

Answer 10

congenital red cell aplasia
present in first year of life - macrocytic, hypoproductive anemia +/- congenital abnormalities

bone marrow has few erythroid precursors, otherwise normal. Also increased eosinophils

most respond to steroids

Question 11

Acquired pure red cell aplasia

Answer 11

rare, can occur w/ thymoma, lymphoma, autoimmune disorders, or after treatment w/ recombinant EPO (formation of Abs against EPO), or after parvo B19 infxn esp in pts w/ chronic hemolytic anemia

Question 12

tx of idiopathic SAA

Answer 12

supportive care - transfusion, judicious use of abx and granulocyte colony stimulating factor (GCSF)

definitive therapy -HSCT or immunosuppressive therapy