5.5 Normocytic Anemias with Extravascular Hemolysis

Question 1

What is the underlying cause of Hereditary Spherocytosis?

Answer 1

Inherited defect in the RBC cytoskeleton-membrane tethering proteins
Most commonly involving ankyrin, spectrin, Band 3.1
Loss of these allows blebs to form in the membrane that are removed by the spleen and this eventually turns the RBC into a sphere-like shape
These cannot maneuver as well through the spleen and are eventually destroyed leading to anemia

Question 2

What cells are infected by parvovirus B19?

Answer 2

Erythroid precursors

Question 3

What are the clinical and lab findings in spherocytosis?

Answer 3

Spherocytes: loss of central pallor
Increased RDW: as RBC’s are chopped up by macrophages, their sizes are going to vary
Increased MCHC: smaller cells have increased concentration of Hb, one of only conditions to have this
Splenomegaly: from macrophage hypertrophy from eating RBC’s
Jaundice: from the increased breakdown of RBC’s, (unconjugated)
Increased risk of bilirubin gallstones
Increased risk of aplastic crisis from B19 virus infection on erythroid precursors

Question 4

How is spherocytosis diagnosed?

Answer 4

Osmotic fragility test: normal RBC’s can handle a little increase in pressure in cell because they have room to swell, spherocytes do not have room to swell and therefore are prone to burst much easier than a normal cell

Question 5

How is spherocytosis treated? What is the outcome?

Answer 5

Splenectomy
Anemia resolves, but the spherocytes persist as they are still processed by other components of the reticuloendothelial system
Howell-Jolly bodies emerge on smear (fragments of nuclear material in RBC’s) these are usually removed by the spleen

Question 6

What is a Howell-Jolly body?

Answer 6

Remnant of nuclear material in an RBC
Usually removed by the spleen, so will show up on smear in patients who do not have a spleen or otherwise have splenic dysfunction

Question 7

What are the three conditions that cause normocytic anemia with extravascular hemolysis?

Answer 7

Extravascular hemolysis seems to be caused by structural abnormalities in the RBC, so think Spherocytosis and Sickle Cell anemia
Also include hemoglobin C

Question 8

Explain the genetics of sickle cell anemia

Answer 8

Autosomal Recessive mutation in the Beta chain of Hb
Disease when both beta globin genes are mutated
Mutation is single non-conservative missense that changes glutamic acid (hydrophilic) to valine (hydrophobic)
Gene carried by 10% of Africans
Protective against malaria falciparum

Question 9

What causes and prevents sickling in sickle cell anemia?

Answer 9

Cause: hypoxemia, dehydration, acidosis

Prevents: HbF protects against sickling, treatment with hydroxyurea increases these levels and can be helpful

Question 10

Why don’t sickle cell patients present with disease until around 6 months of age?

Answer 10

HbF is protective against sickling for the first few months of life

Question 11

In sickle cell anemia, the cells sickle continuously and damage the RBC membrane. What are the effects of this?

Answer 11

1) Extravascular hemolysis: reticuloendothelial system removes RBC’s causing anemia, jaundice, and gallstones
2) Intravascular hemolysis: RBC’s with damaged membranes dehydrate leading to decreased haptoglobin and target cells
3) Massive erythroid hyperplasia: hematopoiesis in skull (crewcut appearance) and facial bones (chipmunk facies), hepatomegaly, aplastic crisis with parvovirus B19

Question 12

What 2 diseases cause massive erythroid hyperplasia leading to crewcut appearance on x-ray and chipmunk facies?

Answer 12

beta-thalassemia major

sickle cell anemia

Question 13

Which anemias have target cells?

Answer 13

sickle cell anemia

beta-thalassemia minor

Question 14

What is the most common presenting Sx in sickle cell anemia?

Answer 14

Dactylitis: swollen hands and feet due to vaso0occlusive infarcts in bones

Question 15

What are the complications of the extensive sickling in sickle cell anemia that leads to vaso-occlusion?

Answer 15

Dactylitis
Autosplenectomy
Acute chest syndrome
Pain crisis
Renal papillary necrosis

Question 16

What is the most common cause of death in kids with sickle cell anemia?

Answer 16

Autosplenectomy puts the kids at risk for infection by encapsulated organisms like S. pneumo and H flu
This is the most common cause of death
Should be vaccinated by 5 years of age
They are also at risk for Salmonella paratyphi osteomyelitis

Question 17

What is the most common cause of death in adults with sickle cell anemia?

Answer 17

Acute chest syndrome:
Vaso-occlusion in pulmonary circulation
Presents with chest pain, sob, lung infiltrates
Often precipitated by pneumonia

Question 18

How does vaso-occlusion in sickle cell anemia affect the kidney?

Answer 18

Causes Renal Papillary Necrosis resulting in gross hematuria and proteinuria

Question 19

What is sickle cell trait? Features of the disease?

Answer 19

Presence of only one mutated Beta globin gene
Generally asymptomatic with no anemia because cells with less than 50% HbS generally don’t sickle in vivo except in the renal medulla
Sickling in the renal medulla happens because of extreme hypoxia and hypertonicity in the region
Microinfarctions in the renal medulla lead to microscopic hematuria at first, followed by an eventual decreased ability to concentrate urine

Question 20

Lab findings in both sickle cell disease and trait

Answer 20

Sickle cells and target cells only seen in the disease and not in the trait
Metabisulfite screen causes cells with any HbS to sickle so + in both cases
Hb electrophoresis confirms presence of HbS

Disease: 90% HbS, 8% HbF, 2% HbA2, No HbA
Trait: 55% HbA, 43% HbS, 2% HbA2
(notice the huge difference in that trait has mostly HbA and disease has none)

Question 21

Hemoglobin C

Answer 21

Autosomal Recessive mutation in beta chain of Hb
Glutamic acid traded out for Lysine (HbC has LyCine)
Mild anemia, extravascular hemolysis
HbC crystals on blood smear