Lec 2 Bone Marrow Failure Flashcards
What is the signature feature of impaired bone marrow production?
decreased reticulocyte count
What will bone marrow aspirate show in leukemia or myelodysplastic syndrome?
cellular marrow filled with leukemia cells or dysplastic cells of MDS
What will bone marrow biopsy show in aplastic anemia?
no hematopoietic cells
What is myelopthisis?
bone marrow is infiltrated –> crowding out/impairment of normal hematopoietic cells
What is normal absolute retic count?
50,000 to 100,000
What is the definition of anemia?
Hgb < 13 in men
Hgb < 12 in women
WHat is the effect of myelopthisis?
have crowding of bone marrow –> pancytopenia
What are some things that can infiltrate the bone marrow?
metastatic cancer
hematologic malignancies
fibrosis
infection
Should you do bone marrow aspirate or bone marrow biopsy if you suspect myelopthisis?
biopsy; infiltrate may cause dry tap if you try to aspirate
What are some characteristic findings in myelopthisis?
- teardrop RBCs in blood
- luekoerythroblastosis = presence of immature WBCs and nucleated RBCs in peripheral blood]
What happens to EPO when you have anemia normally? What about in setting of renal disease?
in anemia EPO rises normally to produce more RBCs
in renal disease –> inadequate EPO –> become more anemic
What is general mech of B12 deficiency?
have impaired DNA production –> impaired cell turnover since B12 needed for normal DNA synthesis
megaloblastic, macrocytic
What is general mech of folic acid deficiency?
have impaired DNA production –> impaired cell turnover since folate is needed for normal DNA synthesis
megaloblastic, macrocytic
What is general mech of iron deficiency?
have impaired heme synthesis –> impaired hemoglobin production + anemia
microcytic, hypochromic
What is general mech of anemia of chronic inflammation?
iron transport impaired –> iron trapping in macrophages –> unavailable for hemoglobin synthesis
normocytic –> microcytic
What is general mech of sideroblastic anemia?
impaired iron utilization –> anemia
microcytic, hypochromic
What is aplastic anemia?
bone marrow failure; loss of hematopoietic cells from bone marrow and fatty replacement
–> pancytopenia, severe anemia, leukopenia, thrombocytopenia
normocytic nonhemolytic anemia
What age group[s] get aplastic anemia? Geography?
- peak in early 20s
- peak again in > 60 yo
- 2-4x higher incidence in east Asia
What is etiology of aplastic anemia?
- 65% idiopathic; may be immune mediated
- radiation and drugs
- virus = infectious
What 2 drugs most commonly associated with aplastic anemia?
- chloramphenicol
- benzene
What are 4 viruses associated with aplastic anemia?
- parvovirus B19
- EBV
- HIV
- HCV
What is mech of parvovirus B19 causing aplastic anemia?
infects and kills RBC precursors –> pure red cell aplasia
What is mech of CMV causing bone failure?
affects immunesuppressed pts; CMV infects stromal cells and interferes w/ growth factor production –> pancytopenia
esp seen in post-bone marrow transplant patients
What is hepatitis-associated aplastic anemia?
occurs after cute non-A; non-B; non-C hepatitis
seen in young males in fare east
likely immune mediated; high mortality
How are telomeres associated w/ aplastic anemia?
mutation of TERC/TERT genes leading to shortened telomeres b/c non-functional telomerase
seen in 30-50% of patients w/ acquired AA
What is the hypothesis of acquired aplastic anemia?
due to immune dyregulation of hepatopoiesis from damaged stem cells leading to loss of proliferative capacity or induction of antigens that trigger immune destruction via cytotoxic T cells
What is clinical definition of severe aplastic anemia?
bone marrow biopsy cellularity < 25% AND 2 of the 3: granulocytes < 500 platelets < 20,000 reticulocytes < 60,000
What is clinical definition of very severe aplastic anemia?
severe aplastic anemia AND granulocytes < 200
What is clinical definition of moderate aplastic anemia?
not severe
stable w/ depressed counts > 3 mos
What are symptoms of aplastic anemia?
fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection
How do people w/ aplastic anemia die?
usually infection
What are possible treatments for aplastic anemia?
- withdrawal offending agent
- supportive
- immunosuppression
- stem cell transplant
- avoid transfusions in transplant candidates
What is the 3 drug immunosuppression medication regimen for aplastic anemia?
antithymocyte globulin + cyclosporine + steroids
What is treatment for aplastic anemia if refractory to antithymocyte globulin?
give eltrombopag = thrombopoietin receptor agonist –> stimulates the few hematopoietic stem cells that are left
What is major complication of aplastic anemics treated with immunosuppression?
have clonal evolution –> 20% go on to MDS/AML [myelodysplastic syndrome] within 10 years; 10% to PNH [paroxysmal nocturnal hemoglobinuria]
What is the most common inherited cause of bone marrow failure?
fanconi anemia
What is the pathogenesis of fanconi anemia?
rare inherited disease causes defect in DNA repair –> increased sensitivity to DNA to physical/chemical damage –> chromosomal breaks
What is mech of paroxysmal nocturnal hemoglobinuria?
acquired stem cell disease due to defect in synthesis of GPI anchor which anchors DAF/CD55 and CD59 proteins which inhibit complement –> increased complement lysis of RBCs
What type of hemolysis in paroxysmal nocturnal hemoglobinuria?
intravascular hemolysis
What is relationship PNH and aplastic anemia?
~ 30% of PNH patients develop aplastic anemia
What are some complications of PNH?
associated with aplastic anemia; increased risk of thrombosis
What is the triad of PNH?
- negative Coobs hemolytic anemia
- pancytopenia
- venous thrombosis
What is treatment of paroxysmal nocturnal hemoglobinuria?
eculizumab
What is the mech of eculizumab?
monoclonal antibody; prevents conversion C5 –> C5a
thus prevents formation of MAC and interferes with complement lysis of RBCs
What do you see on CBC with aplastic anemia?
- low Hb
- low WBCs
- low platelets
- low retic count
- normal B12/folate
What lab tests should you do in patient with aplastic anemia?
- hepatitis screen
- test for PNH [CD55/CD59]
- cytogenic studies
- B12 and folate levels
Why do you want to avoid transfusions in pt with aplastic anemia?
can lead to alloimmunization from foreign antigens on donor blood –> increase risk of transplant rejection
What are the signs/symptoms of fanconi anemia?
cafe au lait spots, hyperpigmentation, short stature, infertility
What is treatment of fanconi anemia?
give androgens
stem cell transplant
What are complications of fanconi anemia?
increased risk of myelodysplasia, AML, epithelial malignancies
stem cell transplant will cure BM failure but not alter risk for developing other malignancies b/c the defect is seen in ALL cells
