10) Hemoglobinopathies & thalassemias

Question 1

hemoglobinopathy

Answer 1

defect in structure of globin chain

Question 2

thalassemia

Answer 2

decreased rate of globin chain synthesis

Question 3

2 alpha 2 beta

Answer 3

Hgb A

Question 4

2 alpha 2 delta

Answer 4

Hgb A2

Question 5

2 alpha 2 gamma

Answer 5

Hgb F

Question 6

2 zeta 2 epsilon

Answer 6

Gower 1

Question 7

2 alpha 2 epsilon

Answer 7

Gower 2

Question 8

2 zeta 2 gamma

Answer 8

Portland

Question 9

𝛼2β2 6 val

Answer 9

Hgb S

valine replaces glutamic acid on Beta

Question 10

conditions under which sickling may occur in sickle trait

Answer 10

anesthesia
strenuous exercise

Question 11

when does Hgb S sickle?

Answer 11

physiological oxygen tensions
deoyxgenation makes cell susceptible to sickling

Question 12

3 factors sickling depends on

Answer 12

• degree of oxygenation
• pH
• dehydration

Question 13

main cause of anemia in sickle cell anemia

Answer 13

extravascular hemolysis
spleen lyses fragile Hgb S cells

Question 14

Hgb S cell lifespan

Answer 14

14 days

Question 15

explain sickle cell crises

Answer 15

vaso-occlusion in capillaries
lower oxygen levels increase sickling
other blood cells & coagulation cascade activated
cell masses obstruct vessels can cause necrosis

Question 16

adults tend to have autosplenectomy due to infarction, so splenomegaly is rare

Answer 16

sickle cell

Question 17

what do inclusions on a PB smear of a sickle cell pt indicate?

Answer 17

autosplenectomy

Question 18

complications of sickle cell

Answer 18

• growth of hands, hips, arms, legs affected
• lung and abdominal infarcts
• hepatomegaly
• leg ulcers near ankles

Question 19

cell found on virtually any hemoglobinopathy smear, even a heterozygous trait

Answer 19

target cells

Question 20

sickle cell disease on PB

Answer 20

• sickle cells
• target cells
• nRBCs
• polychromasia
• aniso & poik
• leukocytosis with left shift
• HJ bodies

Question 21

sickle cell disease lab results

Answer 21

• low H&H
• ↓ osmotic fragility
• positive sickle solubility test (except newborns)
• Hgb electrophoresis—no A, mostly S, increased A2 and F

Question 22

sickle cell disease tx

Answer 22

• pain relief
• rehydration
• antibiotics for secondary infections
• exchange transfusions
• hydroxyurea (↑ Hgb F)

Question 23

𝛼2β2 6 lys

Answer 23

Hgb C

Question 24

usually asymptomatic but may experience joint and abd pain, and splenomegaly

Answer 24

Hgb C disease

Question 25

Hgb C disease on PB

Answer 25

- Hgb C crystals - target cells - aniso - folded/convoluted RBCs

Question 26

Hgb C disease RBC lifespan

Answer 26

30-55 days

Question 27

𝛼2 βS βC

Answer 27

Hgb S/C

Question 28

sickling and crystal formation

Answer 28

Hgb S/C

Question 29

symptoms like mild sickle cell, with prominent splenomegaly

Answer 29

Hgb S/C disease

Question 30

Hgb S/C on PB

Answer 30

- normo/normo - Hgb concentrated on one side of cell "billiard balls" - small, dense, misshapen cells with crystals

Question 31

𝛼2β2 121 gln

Answer 31

Hgb D

Question 32

most common in Indians also African Americans

Answer 32

Hgb D

Question 33

hemoglobinopathy requiring acid electrophoresis to distinguish, because the 2 bands migrate together

Answer 33

Hgb S/D

Question 34

𝛼2β2 26 lys

Answer 34

Hgb E

Question 35

most common in Southeast Asians as well as African Americans

Answer 35

Hgb E

Question 36

2nd most prevalent hemoglobinopathy worldwide

Answer 36

Hgb E

Question 37

↓ oxygen affinity of a given Hgb ----- the effects of anemia

Answer 37

↓

Question 38

hemoglobinopathy that may protect against malaria

Answer 38

Hgb E

Question 39

Hgb E on PB

Answer 39

- micro/hypo - target cells

Question 40

most clinically significant types of thalassemia

Answer 40

those affecting alpha or beta chains

Question 41

# Thalassemia phenotype βO/βO | O means absent

Answer 41

β-thalassemia major

Question 42

# Thalassemia phenotype βO/B+

Answer 42

β-thalassemia major/intermedia

Question 43

# Thalassemia phenotype β+/β+

Answer 43

β-thalassemia major/intermedia

Question 44

# Thalassemia phenotype βO/β

Answer 44

β-thalassemia intermedia/minor

Question 45

# Thalassemia phenotype β+/β

Answer 45

β-thalassemia minor

Question 46

# Thalassemia phenotype βSC/β

Answer 46

β-thalassemia minima (silent carrier)

Question 47

Cooley's anemia

Answer 47

β-thalassemia major

Question 48

attempts to compensate for β-thalassemia major, but has a higher affinity for O2

Answer 48

Hgb F

Question 49

what happens to excess alpha chains in beta thalassemia?

Answer 49

form 𝛼4 aggregates precipitate in normoblast, damaging membrane **causes severe chronic hemolytic anemia**

Question 50

occurs in infants as failure to thrive jaundice hepatosplenomegaly

Answer 50

β-thalassemia around time of switch from 𝛾 to β chains

Question 51

manifestations of β-thalassemia

Answer 51

- infant failure to thrive - jaundice - hepatosplenomegaly - siderosis - "hair on end" bone structure - thick jaw, concave nose

Question 52

β-thalassemia CBC

Answer 52

- low H & H - micro/hypo - MCV in 50s or 60s - retics normal or low - RBCs may be elevated

Question 53

β-thalassemia on PB

Answer 53

- target cells - micro/hypo - marked aniso, poik - nRBCs - variable basophilic stippling - polychromasia

Question 54

micro/hypo anemia with slightly decreased hgb, MCV in 50-70 range, and high RBC count (>5)

Answer 54

β-thalassemia minor

Question 55

homozygotes have 100% Hgb F micro/hypo anemia

Answer 55

𝜹β-thalassemia

Question 56

hereditary persistence of fetal hemoglobin is a form of...

Answer 56

β-thalassemia

Question 57

100% Hgb F with ↑ RBC count and ↑ Hgb

Answer 57

HPFH

Question 58

2 types of HPFH on Kleihauer-Betke stain populations associated

Answer 58

- **Pancellular** - most RBCs contain Hgb F - Black and Greek pop - **Heterocellular** - 3% RBCs contain Hgb F - Swiss pop

Question 59

normal 𝛼 chain combined with abnormal 𝜹β chain resulting from genetic crossover

Answer 59

Hgb Lepore

Question 60

how does Hgb Lepore lead to anemia?

Answer 60

𝜹β chain is synthesized at a slow rate, leading to hematologic changes that resemble thalassemia

Question 61

major Hgb seen with Hgb Lepore disease

Answer 61

Hgb F

Question 62

tx for β-thalassemias

Answer 62

- splenectomy - regular transfusions - iron chelating agents

Question 63

4 clinical phenotypes of 𝛼-thalassemia

Answer 63

- hydrops fetalis - Hgb H disease - 𝛼-thal minor - silent carrier

Question 64

# Thalassemia phenotype (--/--)

Answer 64

hydrops fetalis

Question 65

# Thalassemia phenotype (--/-𝛼)

Answer 65

Hgb H disease

Question 66

# Thalassemia phenotype (--/𝛼𝛼) (-𝛼/-𝛼)

Answer 66

𝛼-thal minor

Question 67

# Thalassemia phenotype (-𝛼/𝛼𝛼)

Answer 67

silent carrier

Question 68

𝛾4 (no 𝛼 to combine with)

Answer 68

Hgb Barts sickling Hgb

Question 69

population associated with hydrops fetalis

Answer 69

Asian

Question 70

β4 (no 𝛼 to combine with)

Answer 70

Hgb H

Question 71

Hgb H disease on PB

Answer 71

- micro/hypo - target cells - ↑ retic - nRBCs

Question 72

inclusions can be seen by staining with **brilliant cresyl blue**, showing **golf ball** appearance

Answer 72

Hgb H

Question 73

MCV 50-60 RBC >5 occasional Hgb H inclusions

Answer 73

𝛼-thal minor