2 - Stem Cell Hematopoiesis and Bone Marrow Failure Flashcards
sites of early hematopoiesis
yolk sac blood islands (16 d) aortogonadomesonephros (20-30 d) liver (6 w) bone marrow (5 mo - postnatal) thymus (T cell development)
lymphoid derived cells
T, B, NK, dendritic
myeloid derived cells
RBCs, megakaryocytes/platelets, monocytes/macrophages, granulocytes
3 important characteristics of hematopoietic stem cells
multipotent
self renewing
quiescent (only divide when needed)
what class of signaling molecules are responsible for directing stem cell trafficking?
cytokines
severe aplastic anemia (SAA) definition
bone marrow hypocellularity (<20k)
5 categories of causes for pancytopenia
HSC injury clonal hematopoietic cell mutation myelophthisis (BM infiltration) defective maturation enhanced peripheral destruction
causes of bone marrow failure
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)
Fanconi anemia
AR inheritance, variable phenotype
DNA repair disorder
cafe au lait spots, microophthalmia, abnormal thumbs, predisposed to AML/MDS and other cancers
Diamond Blackfan anemia
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
Acquired pure red cell aplasia
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
tx of idiopathic SAA
supportive care - transfusion, judicious use of abx and granulocyte colony stimulating factor (GCSF)
definitive therapy -HSCT or immunosuppressive therapy