Lec 2 Bone Marrow Failure

Question 1

What is the signature feature of impaired bone marrow production?

Answer 1

decreased reticulocyte count

Question 2

What will bone marrow aspirate show in leukemia or myelodysplastic syndrome?

Answer 2

cellular marrow filled with leukemia cells or dysplastic cells of MDS

Question 3

What will bone marrow biopsy show in aplastic anemia?

Answer 3

no hematopoietic cells

Question 4

What is myelopthisis?

Answer 4

bone marrow is infiltrated –> crowding out/impairment of normal hematopoietic cells

Question 5

What is normal absolute retic count?

Answer 5

50,000 to 100,000

Question 6

What is the definition of anemia?

Answer 6

Hgb < 13 in men

Hgb < 12 in women

Question 7

WHat is the effect of myelopthisis?

Answer 7

have crowding of bone marrow –> pancytopenia

Question 8

What are some things that can infiltrate the bone marrow?

Answer 8

metastatic cancer
hematologic malignancies
fibrosis
infection

Question 9

Should you do bone marrow aspirate or bone marrow biopsy if you suspect myelopthisis?

Answer 9

biopsy; infiltrate may cause dry tap if you try to aspirate

Question 10

What are some characteristic findings in myelopthisis?

Answer 10

• teardrop RBCs in blood

- luekoerythroblastosis = presence of immature WBCs and nucleated RBCs in peripheral blood]

Question 11

What happens to EPO when you have anemia normally? What about in setting of renal disease?

Answer 11

in anemia EPO rises normally to produce more RBCs

in renal disease –> inadequate EPO –> become more anemic

Question 12

What is general mech of B12 deficiency?

Answer 12

have impaired DNA production –> impaired cell turnover since B12 needed for normal DNA synthesis

megaloblastic, macrocytic

Question 13

What is general mech of folic acid deficiency?

Answer 13

have impaired DNA production –> impaired cell turnover since folate is needed for normal DNA synthesis

megaloblastic, macrocytic

Question 14

What is general mech of iron deficiency?

Answer 14

have impaired heme synthesis –> impaired hemoglobin production + anemia

microcytic, hypochromic

Question 15

What is general mech of anemia of chronic inflammation?

Answer 15

iron transport impaired –> iron trapping in macrophages –> unavailable for hemoglobin synthesis

normocytic –> microcytic

Question 16

What is general mech of sideroblastic anemia?

Answer 16

impaired iron utilization –> anemia

microcytic, hypochromic

Question 17

What is aplastic anemia?

Answer 17

bone marrow failure; loss of hematopoietic cells from bone marrow and fatty replacement
–> pancytopenia, severe anemia, leukopenia, thrombocytopenia

normocytic nonhemolytic anemia

Question 18

What age group[s] get aplastic anemia? Geography?

Answer 18

• peak in early 20s
• peak again in > 60 yo
• 2-4x higher incidence in east Asia

Question 19

What is etiology of aplastic anemia?

Answer 19

• 65% idiopathic; may be immune mediated
• radiation and drugs
• virus = infectious

Question 20

What 2 drugs most commonly associated with aplastic anemia?

Answer 20

• chloramphenicol

- benzene

Question 21

What are 4 viruses associated with aplastic anemia?

Answer 21

• parvovirus B19
• EBV
• HIV
• HCV

Question 22

What is mech of parvovirus B19 causing aplastic anemia?

Answer 22

infects and kills RBC precursors –> pure red cell aplasia

Question 23

What is mech of CMV causing bone failure?

Answer 23

affects immunesuppressed pts; CMV infects stromal cells and interferes w/ growth factor production –> pancytopenia

esp seen in post-bone marrow transplant patients

Question 24

What is hepatitis-associated aplastic anemia?

Answer 24

occurs after cute non-A; non-B; non-C hepatitis

seen in young males in fare east

likely immune mediated; high mortality

Question 25

How are telomeres associated w/ aplastic anemia?

Answer 25

mutation of TERC/TERT genes leading to shortened telomeres b/c non-functional telomerase seen in 30-50% of patients w/ acquired AA

Question 26

What is the hypothesis of acquired aplastic anemia?

Answer 26

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

Question 27

What is clinical definition of severe aplastic anemia?

Answer 27

``` bone marrow biopsy cellularity < 25% AND 2 of the 3: granulocytes < 500 platelets < 20,000 reticulocytes < 60,000 ```

Question 28

What is clinical definition of very severe aplastic anemia?

Answer 28

severe aplastic anemia AND granulocytes < 200

Question 29

What is clinical definition of moderate aplastic anemia?

Answer 29

not severe | stable w/ depressed counts > 3 mos

Question 30

What are symptoms of aplastic anemia?

Answer 30

fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection

Question 31

How do people w/ aplastic anemia die?

Answer 31

usually infection

Question 32

What are possible treatments for aplastic anemia?

Answer 32

- withdrawal offending agent - supportive - immunosuppression - stem cell transplant - avoid transfusions in transplant candidates

Question 33

What is the 3 drug immunosuppression medication regimen for aplastic anemia?

Answer 33

antithymocyte globulin + cyclosporine + steroids

Question 34

What is treatment for aplastic anemia if refractory to antithymocyte globulin?

Answer 34

give eltrombopag = thrombopoietin receptor agonist --> stimulates the few hematopoietic stem cells that are left

Question 35

What is major complication of aplastic anemics treated with immunosuppression?

Answer 35

have clonal evolution --> 20% go on to MDS/AML [myelodysplastic syndrome] within 10 years; 10% to PNH [paroxysmal nocturnal hemoglobinuria]

Question 36

What is the most common inherited cause of bone marrow failure?

Answer 36

fanconi anemia

Question 37

What is the pathogenesis of fanconi anemia?

Answer 37

rare inherited disease causes defect in DNA repair --> increased sensitivity to DNA to physical/chemical damage --> chromosomal breaks

Question 38

What is mech of paroxysmal nocturnal hemoglobinuria?

Answer 38

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

Question 39

What type of hemolysis in paroxysmal nocturnal hemoglobinuria?

Answer 39

intravascular hemolysis

Question 40

What is relationship PNH and aplastic anemia?

Answer 40

~ 30% of PNH patients develop aplastic anemia

Question 41

What are some complications of PNH?

Answer 41

associated with aplastic anemia; increased risk of thrombosis

Question 42

What is the triad of PNH?

Answer 42

- negative Coobs hemolytic anemia - pancytopenia - venous thrombosis

Question 43

What is treatment of paroxysmal nocturnal hemoglobinuria?

Answer 43

eculizumab

Question 44

What is the mech of eculizumab?

Answer 44

monoclonal antibody; prevents conversion C5 --> C5a thus prevents formation of MAC and interferes with complement lysis of RBCs

Question 45

What do you see on CBC with aplastic anemia?

Answer 45

- low Hb - low WBCs - low platelets - low retic count - normal B12/folate

Question 46

What lab tests should you do in patient with aplastic anemia?

Answer 46

- hepatitis screen - test for PNH [CD55/CD59] - cytogenic studies - B12 and folate levels

Question 47

Why do you want to avoid transfusions in pt with aplastic anemia?

Answer 47

can lead to alloimmunization from foreign antigens on donor blood --> increase risk of transplant rejection

Question 48

What are the signs/symptoms of fanconi anemia?

Answer 48

cafe au lait spots, hyperpigmentation, short stature, infertility

Question 49

What is treatment of fanconi anemia?

Answer 49

give androgens | stem cell transplant

Question 50

What are complications of fanconi anemia?

Answer 50

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