Topic 4: Hereditary Spherocytosis

Question 1

what is hereditary spherocytosis?

Answer 1

inherited condition that results in spherocytes

RBCs are in the shape of a sphere which renders them susceptible to getting engulfed by macrophages in certain areas, particularly the spleen

this leads to the breakdown of RBCs in the spleen (extravascular hemolysis) and anemia

Question 2

Where do RBCs undergo hemolysis in HS?

Answer 2

spleen

Question 3

why are RBCs sphere shaped in HS?

Answer 3

a defect in proteins that make up the RBC cytoskeleton (such as spectrin and ankyrin)

or

defect in proteins that anchor the cytoskeleton to the RBC membrane (such as band 3, band 4.1, or band 4.2)

without stable cytoskeleton or stable anchoring of the membrane to the cytoskeleton, the RBC membrane starts to bleb and fall off to form a sphere

Question 4

what is the effect of spherical RBCs?

Answer 4

macrophages engulf these abnormal RBCs, resulting in extravascular hemolysis with an unconjugated hyperbilirubinemia

also splenomegaly because the spleen is doing a lot of work trying to get rid of all the weird RBCs

Question 5

how is spherocyte oxygen carrying capacity effected?

Answer 5

trick question, it’s not!

these RBCs function perfectly with respect to oxygen carrying

Question 6

Which proteins are most commonly defective in HS?

Answer 6

spectrin, ankyrin, band 3, band 4.1 or band 4.2

Question 7

What is the classic triad that patients present with in HS?

Answer 7

• mild anemia
• intermittent jaundice
• splenomegaly

Question 8

what virus are HS patients at risk for?

Answer 8

parvovirus B19

due to a limited supply of RBCs

parvovirus B19 virus infects immature progenitor cells in the bone marrow (RBCs, white blood cells, and platelets) and causes cell lysis

cell lysis in combination with reduced half-life due to spherical shape of RBC results in anemia

Question 9

what does the blood smear of a HS patient show?

Answer 9

spherocytes

Question 10

what does the CBC of an HS patient show?

Answer 10

• low Hb
• low Hct
• elevated RDW
• elevated MCHC
• elevated serum LDH
• indirect/unconjugated hyperbilirubinemia

Question 11

how is RDW effected in HS?

Answer 11

elevated

because older cells
have lost a lot of membrane (and are therefore smaller)

whereas younger
cells have lost relatively little membrane (and are therefore larger)

Question 12

how is MCHC effected in HS?

Answer 12

elevated

mean corpuscular hemoglobin concentration measures average concentration of Hb present in a RBC

this is because as portions of the RBC membrane are lost, the RBCs become smaller, and the concentration of Hb within those cells increases

Question 13

what test can be done to confirm the present spherocytes?

Answer 13

osmotic fragility test

**note that spherocytes can be seen in other conditions as well, so this test does not necessarily confirm the diagnosis of HS

Question 14

what does the osmotic fragility test do?

Answer 14

measures how well the red blood cells can handle being placed in a hypotonic solution (which will cause water to flow into the cell by osmosis)

normal RBCs have plenty of room to accommodate an influx of water

RBCs in HS will burst in hypotonic solution when water goes in because a ton of the membrane has been lost and there’s not as much space inside

Question 15

What are the confirmatory tests in HS?

Answer 15

1. Osmotic fragility test

2. eosin-5-maleimide binding test: can test for membrane defects via flow cytometry

Question 16

what can be done to treat HS?

Answer 16

since the only place RBCs are being destroyed is the spleen you can do a splenectomy to remove the spleen - spherocytes will persist then

this is the most common treatment

but since most patients have such a mild hemolysis, splenectomy is reserved for patients with severe HS

Question 17

what’s the drawback to a splenectomy?

Answer 17

you need vaccinations against encapsulated organisms