9) Aplastic and hypoproliferative anemias

Question 1

morphologic and BM characteristics of hypoproliferative/aplastic anemias

Answer 1

normocytic normochromic
hypocellular marrow

aplasia —pancytopenia (precursor affected)

Question 2

parts of aplastic anemia dx (4)

Answer 2

• BM <25% cellularity
• ANC <0.5
• platelets <20
• corrected retic <1% (no compensation)

Question 3

2 age groups affected by aplastic anemia

Answer 3

young (<20) - usually idiopathic
older (>60) - usually secondary

Question 4

4 general pathophysiologies of aplastic anemia

Answer 4

• immune suppression (autoimmunity)
• abnormal/deficient HSCs
• bone marrow matrix defects
• deficient GFs (not sole cause)

Question 5

2 general categories of aplastic anemia and causes in both

Answer 5

Acquired
Idiopathic
Drugs
Chemicals
Radiation
Infectious agents
Metabolic errors
Paroxysmal nocturnal hemoglobinuria

Constitutional/congenital
Fanconi’s anemia
Familial aplastic anemia

Question 6

chloramphenicol
phenobutazone

Answer 6

acquired aplastic anemia

Question 7

benzene derivatives (inhibit DNA synth)

Answer 7

acquired aplastic anemia

Question 8

this treatment does not work for radiation-related aplasic anemia

why?

Answer 8

BM transplant

the anemia is due to a matrix change in the BM

Question 9

infectious agents that can cause aplastic anemia

Answer 9

TB
EBV
CMV
HIV
parvovirus (limited to RBCs)
hepatitis (not known viruses)

Question 10

infection-related aplastic anemia that is often fatal

Answer 10

hepatitis

Question 11

metabolic errors that lead to accumulation of ketones and glycine can cause…

Answer 11

aplastic anemia

Question 12

explain PNH

Answer 12

membrane abnormality
lipid that protects cells from complement lysis is absent
cells lyse at night when pH in kidney drops

Question 13

autosomal recessive, slowly progressive aplastic anemia

Answer 13

Fanconi’s anemia

Question 14

Fanconi’s anemia s/s

Answer 14

• bone dysplasia
• renal abnormalities
• organ malformations
• mental retardation
• dwarfism
• microcephaly
• hypogonadism
• skin hyperpigmentation
• thumb abnormalities
• strabismus

Question 15

Fanconi’s effects on blood cells

Answer 15

• platelets fall first, and get critically low
• decrease in granulocytes
• neutrophils get large pink granules
• macrocytosis occurs before anemia

Question 16

Fanconi’s therapies

Answer 16

• Androgen tx — reverse pancytopenia for several years
• BM transplant

Question 17

Fanconi’s median survival age

Answer 17

30

Question 18

aplastic anemia
specific inheritance pattern uknown

Answer 18

familial aplastic anemia

Question 19

clinical findings of aplastic anemia

Answer 19

• insidious, gradual progression
• bleeding, anemia, infection
• usually no organomegaly

Question 20

PB findings in aplastic anemia

Answer 20

• pancytopenia
• normocytic, normochromic
• corrected retic <1%, no compensation
• platelets decrease first, then neutrophils, then WBCs
• relative lymphocytosis due to decreased neutros
• neutrophil granules that are large and stain dark red

Question 21

BM findings in aplastic anemia

Answer 21

• hypocellular, >70% fat —dry tap
• macrophages with Fe, but no siderocytes

Question 22

dry tap

Answer 22

aplastic anemia

Question 23

fetal characteristics of RBCs (Hgb F, i antigens)

Answer 23

aplastic anemia
Diamond-Blackfan syndrome

Question 24

iron and EPO in aplastic anemia

Answer 24

EPO ↑
serum Fe ↑
% sat ↑

Question 25

cure for aplastic anemia

Answer 25

BM transplant

Question 26

survival rate for aplastic anemia

Answer 26

2 years for 60-90%

Question 27

3 other disorders important to differentially diagnose from aplastic anemia

Answer 27

- myelophthisic anemia - myelodysplastic syndrome (MDS) - congenital dyserythropoietic anemia (CDA)

Question 28

characteristics of myelophthisic anemia

Answer 28

- BM **"crowded out"** by fibrotic, granulomatous or neoplastic cells - **tear drops** - giant platelets - poik - nRBCs and left shift (**leukoerythroblastosis**)

Question 29

characteristics of MDS

Answer 29

- "preleukemia", tends to end in leukemia - cytopenia with ↓ retic - **BM is normocellular or hypercellular**, with **dyshematopoiesis** (weird BM cells) — cells lyse before release into PB

Question 30

characteristics of CDA

Answer 30

- abnormal and ineffective erythropoiesis - rare, familial, refractory anemia - BM is normocellular or hypocellular - pancytopenia - **myeloblasts** and **promyelocytes** - **RBC precursors multinucleated** - **macrocytic** anemia

Question 31

3 types of pure red cell aplasia

Answer 31

- acquired acute PRC aplasia - acquired chronic PRC aplasia - diamond-blackfan syndrome

Question 32

general s/s of pure red cell aplasia

Answer 32

- ↓ RBC, Hct, Hgb - Corrected retic <1% - ↑M:E ratio in BM - ↑EPO

Question 33

parvovirus B19, Fifth disease hepatitis (poor prognosis) other infections

Answer 33

acquired acute pure red cell aplasia

Question 34

worst prognosis for acquired acute PRC aplasia

Answer 34

with hepatitis

Question 35

transient erythroblastopenia of childhood is a type of...

Answer 35

acquired acute PRC aplasia

Question 36

autoimmune disorders thymoma middle age

Answer 36

acquired chronic PRC aplasia

Question 37

rare, congenital, progressive RBC aplasia

Answer 37

diamond-blackfan syndrome

Question 38

characteristics of diamond-blackfan

Answer 38

- very young children - severe anemia - ↑i Ag, ↑ Hgb F - 100% sat, ↑ serum Fe, ↑ ferritin - ↑EPO - minor abnormalities of head and arms

Question 39

distinguish Diamond-blackfan from TEC

Answer 39

↑i Ag, ↑ Hgb F found only in diamond-blackfan

Question 40

most common cause of non-aplastic, non-pure RBC hypoproliferative anemias

Answer 40

↓ EPO

Question 41

can result in normo/normo, megaloblastic, or micro/hypo anemia how?

Answer 41

renal disease ↓ EPO — normo/normo dialysis ↓ folate — megaloblastic dialysis ↓ iron — micro/hypo IDA

Question 42

high BUN and creatinine often causes...

Answer 42

burr cells

Question 43

how can endocrine abnormalities cause a hypoproliferative normo/normo anemia?

Answer 43

hypothyroidism/hypopituitarism ↓ O2 demand in tissues indirectly ↓ EPO

Question 44

anemia occuring in patients with chronic infection, inflammation, or neoplasms

Answer 44

anemia of chronic disease/inflammation

Question 45

iron in ACD patients

Answer 45

↓ serum Fe normal or ↑ Fe stores ↑ ferritin ↓ TIBC

Question 46

second most common anemia

Answer 46

ACD

Question 47

3 mechanisms of ACD

Answer 47

1. cytokines released by inflammatory response **inhibit EPO**, and cell response to EPO 2. hepcidin **blocks Fe mobilization**, so macrophages are unable to give it up for use 3. **early phagocytosis** of good RBCs leads to shortened lifespan (extracorpuscular factors)

Question 48

PB findings in ACD

Answer 48

- mild anemia (Hgb ≥9) - normo/normo, but eventually micro/hypo - RPI <2 - normal WBC, normal platelets

Question 49

BM findings in ACD | not necessary for dx

Answer 49

- ↑ M:E ratio - ↑ hemosiderin in macrophages

Question 50

malignancy can cause a -------------- anemia when it infiltrates the BM

Answer 50

myelophthisic

Question 51

2 main types of anemia of liver disease and characteristics

Answer 51

- chronic liver disease (target cells, acanthocytes from altered lipid metabolism) - alcoholism (megaloblastic, hemolytic anemia)