Ch5 - 5) Normocytic anemia with predominant extravascular hemolysis

Question 1

What are the normocytic anemias with predominant extravascular hemolysis?

Answer 1

1) hereditary spherocytosis 2) Sickle cell anemia 3) Hemoglobin C

Question 2

What is hereditary spherocytosis?

Answer 2

Inherited defect of RBC cytoskeleton-membrane tethering proteins

Question 3

What does hereditary spherocytosis most commonly involve?

Answer 3

spectrin, ankyrin, or band 3.1

Question 4

What is seen in hereditary shperocytosis?

Answer 4

membrane blebs are formed and lost over time

Question 5

In hereditary spherocytosis what happens due to loss of the membrane?

Answer 5

It renders cells round (spherocytes) instead of disc-shaped.

Question 6

How does hereditary spherocytosis lead to anemia?

Answer 6

Spherocytes are less able to maneuver through splenic sinusoids and are consumed by splenic macrophages, resulting in anemia.

Question 7

What do the clinical and laboratory findings for hereditary spherocytosis include?

Answer 7

1) Spherocytes with loss of central pallor, 2) increased RDW and increased mean corpuscular hemoglobin concentration (MCHC) 3) Splenomegaly, jaundice with unconjugated bilirubin, and increased risk for bilirubin gallstones (extravascular hemolysis) 4) Increased risk for aplastic crisis with parvovirus B19 infection of erythroid

Question 8

How is hereditary spherocytosis diagnosed?

Answer 8

by osmotic fragility test, which reveals increased spherocyte fragility in hypotonic solution

Question 9

What is the treatment for hereditary spherocytosis?

Answer 9

splenectomy; anemia resolves, but spherocytes persist and Howell Tolly bodies emerge on blood smear

Question 10

What are Howell Tolly bodies?

Answer 10

fragments of nuclear material in RBCs – appears on blood smear

Question 11

What is sickle cell anemia?

Answer 11

Autosomal recessive mutation in beta chain of hemoglobin; a single amino acid change replaces normal glutamic acid (hydrophilic) with valine (hydrophobic).

Question 12

Who carries the gene for sickle cell anemia?

Answer 12

it is carried by 10% of individuals of African descent, likely due to protective role against falciparum malaria.

Question 13

When does sickle cell disease arise?

Answer 13

When two abnormal beta genes are present; results in >90% HbS in RBCs

Question 14

What causes the formation of the sickle cell structure?

Answer 14

HbS polymerizes when deoxygenated; polymers aggregate into needle-like structures, resulting in sickle cells

Question 15

When is there increased risk of sickling?

Answer 15

hypoxemia, dehydration, and acidosis.

Question 16

Is sickle cell seen at birth?

Answer 16

HbF protects against sickling; high HbF at birth is protective for the first few months of life.

Question 17

What is the treatment for sickle cell anemia?

Answer 17

hydroxyurea increases levels of HbF

Question 18

In sickle cell anemia, what happens to cells as it passes through microcirculation?

Answer 18

The cells sickle and de-sickle while passing through the microcirculation, resulting in complications related to RBC membrane damage.

Question 19

How does sickle cell anemia interact with the reticuloendothelial system?

Answer 19

intravascular hemolysis where the reticuloendothelial system removes RBCs with damaged membranes, leading to anemia, jaundice with unconjugated hyperbilirubinemia, and increased risk for bilirubin gallstones.

Question 20

How does sickle cell anemia lead to decreased haptoglobin and target cells on blood smear?

Answer 20

Intravascular hemolysis where RBCs with damaged membranes dehydrate, leading to hemolysis with decreased haptoglobin and target cells on blood smear

Question 21

Massive erythroid hyperplasia ensues in sickle cell anemia resulting in what?

Answer 21

1) Expansion of hematopoiesis into the skull (‘crewcut’ appearance on x-ray) and facial bones (‘chipmunk fades’). 2) Extramedullar hematopoiesis with hepatomegaly 3) Risk of aplastic crisis with parvovirus B19 infection of erythroid precursors

Question 22

What does irreversible sickling lead to?

Answer 22

complications of vaso-occlusion

Question 23

What are the complications of vasso-occlusion resulting from irreversible sickling?

Answer 23

1) Dactylitis 2) autosplenectomy 3) acute chest syndrome 4) Pain crisis 5) Renal papillary necrosis

Question 24

What is dactylitis?

Answer 24

swollen hands and feet due to vaso-occlusive infarcts in bones; common presenting sign in infants

Question 25

What is autosplenectomy, and what are the consequences?

Answer 25

shrunken, fibrotic spleen. Consequences include: 1) Increased risk of infection with encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae (most common cause of death in children); affected children should be vaccinated by 5 years of age. 2) Increased risk of Salmonella paratyphi osteomyelitis 3) Howell-Jolly bodies on blood smear

Question 26

What is the most common cause of death in children sickle cell patients?

Answer 26

autosplenectomy

Question 27

What is acute chest syndrome?

Answer 27

vaso-occlusion in pulmonary microcirculation

Question 28

What does acute chest syndrome present with?

Answer 28

Presents with chest pain, shortness of breath, and lung infiltrates

Question 29

Acute chest syndrome is often precipitated by?

Answer 29

Often precipitated by pneumonia

Question 30

What is the most common cause of death in adult sickle cell patients?

Answer 30

Acute chest syndrome

Question 31

Renal papillary necrosis results in what?

Answer 31

gross hematuria and proteinuria

Question 32

What is the sickle cell trait?

Answer 32

It is the presence of one mutated and one normal beta chain;

Question 33

What does presence of the sickle cell trait results in?

Answer 33

<50% HbS in RBCs (HbA is slightly more efficiently produced than HbS)

Question 34

How does the sickle cell trait present?

Answer 34

Generally asymptomatic with no anemia; RBCs with < 50%, HbS do not sickle in vivo except in the renal medulla.

Question 35

When would sickling occur in the sickle cell trait?

Answer 35

Extreme hypoxia and hypertonicity of the medulla cause sickling,

Question 36

In the sickling trait what happens?

Answer 36

microinfarctions leading to microscopic hematuria and, eventually, decreased ability to concentrate urine,

Question 37

What are the laboratory findings for the sickle cell trait?

Answer 37

1) Blood smear shows no sickle cells and target cells (unlike sickle cell disease) 2) Metabisulfite screen causes cells with any amount of HbS to sickle; positive in both disease and trait 3) Hb electrophoresis confirms the presence and amount of HbS.

Question 38

What does Hb electrophoresis show in sickle cell disease?

Answer 38

90% HbS, 8% HbF, 2% HbA2 (no HbA)

Question 39

What does Hb electrophoresis show in sickle cell trait?

Answer 39

55% HbA, 43% HbS, 2% HbA2

Question 40

What is hemoglobin C?

Answer 40

Autosomal recessive mulalion in beta chain of hemoglobin

Question 41

What amino acid is affected in hemoglobin C?

Answer 41

Normal glutamic acid is replaced by lysine

Question 42

How common is Hemoglobin C?

Answer 42

It is less common than sickle cell disease

Question 43

What does hemoglobin C present with?

Answer 43

presents with mild anemia due to extravascular hemolysis

Question 44

In Hemoglobin C what is seen on blood smear?

Answer 44

Characteristic HbC crystals are seen in RBCs on blood smear