5.5 Normocytic anemias with extravascular Hemolysis

Question 1

What, generally, is hereditary spherocytosis?

Answer 1

Mutation in the cytoskeletal components of RBCs, causing them to bulge into spheres d/t loss of membrane blebs

Question 2

What are the cytoskeletal tethering proteins that are defective in hereditary spherocytosis? (3)

Answer 2

• Spectrin
• Ankyrin
• Band 3.1

Question 3

What is the RDW with hereditary spherocytosis? Why?

Answer 3

Large, since there is a large variation between new and old RBCs

Question 4

What causes the anemia with hereditary spherocytosis?

Answer 4

RBCs are consumed by the macrophages in the spleen

Question 5

What happens to the MCHC with hereditary spherocytosis? Why?

Answer 5

Increases–Same amount of Hb in a smaller RBC

Question 6

What are the clinical features of hereditary spherocytosis?

Answer 6

• Splenomegaly
• Jaundice with unconjugated bili
• Increased risk for bilirubin gallstones

Question 7

There is an increased risk of aplastic crisis in patients with hereditary spherocytosis with what infectious disease? Why?

Answer 7

Parvovirus B19–infects the erythroid precursors

Question 8

What causes the splenomegaly with hereditary spherocytosis?

Answer 8

Work hypertrophy

Question 9

What is the classic test to diagnose hereditary spherocytosis? What is the basis for this?

Answer 9

Osmotic fragility test–Increased fragility in a hypotonic solution, since the loss of membrane that occurs with hereditary spherocytosis leaves no room for excess water to accumulate.

Question 10

What is the treatment for hereditary spherocytosis?

Answer 10

Splenectomy

Question 11

What are the classic peripheral blood smear findings with a splenectomy? What causes this?

Answer 11

Howell-Jolly bodies–lack of removal of DNA from RBCs due to a loss of splenic macrophages

Question 12

What is the problem that occurs in sickle cell anemia? Inheritance pattern?

Answer 12

AR mutation in the beta globin chain, where a glutamic acid is replaced with a valine

Question 13

What causes the RBCs to sickle with sickle cell anemia?

Answer 13

Hydrophobic valine patch causes RBCs to stick together to hide hydrophobic patch away from water in the serum

Question 14

What is the supposed benefit of sickle cell anemia?

Answer 14

Protection against falciparum malaria

Question 15

When does sickle cell disease result, as opposed to sickle cell trait?

Answer 15

Trait = one mutated beta globin gene

Disease = both beta globin genes are mutated

Question 16

What are the components of HbS?

Answer 16

Alpha-2 beta (S) 2

Question 17

HbS polymerize with under what conditions? (3)

Answer 17

• Deoxygenation
• Dehydration
• Acidosis

Question 18

What is the role of HbF in sickle cell disease?

Answer 18

• Protective factor in the first few months of life

- Hydroxyurea increases levels of HbF

Question 19

What is the role of hydroxyurea in the treatment of sickle cell anemia?

Answer 19

Increases levels of HbF

Question 20

What is the problem that occurs with constant cycling of sickling seen with HbS?

Answer 20

Results in damage to the RBC membrane, leading to decreased flexibility

Question 21

What are the clinical characteristics of sickle cell anemia?

Answer 21

• Anemia
• Jaundice with unconjugated bili
• Increased risk for bili gallstones

Question 22

What happens to haptoglobin levels with sickle cell disease?

Answer 22

Decreased due to intravascular hemolysis

Question 23

What are the PBS findings with sickle cell disease? Why?

Answer 23

• Target cells

- Dehydration of cells causes blebbing of RBCs with Hb accumulation in the blebs

Question 24

What are findings of the erythroid hyperplasia seen with sickle cell disease?

Answer 24

Chipmunk facies

• Crewcut appearance of the skull on x-ray
• HSM

Question 25

What are the complications that arise from the irreversible sickling that is seen with sickle cell disease?

Answer 25

Vasoocclusion and infarction of tissues

Question 26

What is the common presenting sign of sickle cell disease in infants? Why?

Answer 26

Dactylitis--Vaso-occlusive infarct of bones with sickling

Question 27

What causes the autosplenectomy seen with sickle cell disease?

Answer 27

Infarction of the spleen from vasoocclusion by sickled RBCs

Question 28

What bacteria is the classic cause of osteomyelitis with sickle cell disease?

Answer 28

Salmonella paratyphi

Question 29

What are the characteristics PBS findings with splenectomy?

Answer 29

Howell-Jolly bodies

Question 30

What are the SHINE SKiS bacteria that patients with sickle cell disease are susceptible to?

Answer 30

- Strep pneumo - HiB - Neisseria meningitidis - E. Coli - Salmonella - Klebsiella - GBS

Question 31

What is the most common cause of osteomyelitis overall?

Answer 31

Staph aureus

Question 32

What is the acute chest syndrome seen with sickle cell disease? What are the s/sx of this?

Answer 32

- Vaso-occlusion in the pulmonary microcirculation | - Chest pain, SOB

Question 33

What is the most common cause of death with sickle cell disease?

Answer 33

Acute chest syndrome

Question 34

What usually precipitates episodes of acute chest syndrome in patients with sickle cell disease? Why?

Answer 34

- Pneumonia - Causes vasodilation, which increases transit time for RBCs, and increases the chances that sickled RBCs will sickle and occlude

Question 35

What are the renal sequelae of sickle cell disease? How does this present?

Answer 35

- Renal papillary necrosis | - Gross hematuria and proteinuria

Question 36

How much HbS is needed to cause sickling? Why is this relevant?

Answer 36

More than 50% | -Explains why sickle cell trait does not lead to the same issues as sickle cell disease

Question 37

Generally, RBCs in sickle cell trait do not sickle, and thus do not cause problems. There is one exception to this however. What is this? Why?

Answer 37

Renal medulla has extreme hypoxia and hypertonicity, causing microinfarctions, leading to progressive kidney damage

Question 38

What are the clinical findings of renal medulla damage with sickle cell trait?

Answer 38

- Microscopic hematuria | - Decreased ability to concentrate urine

Question 39

What is the chemical that can cause cells to sickle if HbS is present at all?

Answer 39

Metabisulfite

Question 40

What happens to HbA with sickle cell disease?

Answer 40

Absent

Question 41

What is the amino acid change that occurs with hemoglobin C? What is the inheritance pattern of this?

Answer 41

- AR mutation in beta chain | - Glutamic acid to lysine ("lys-ccc-ene")

Question 42

What is the classic PBS finding of HbC?

Answer 42

Hb C crystals