Primer 11 - Hemolytic Anemias

Question 1

What lowers Haptoglobin (Hp) levels?

Answer 1

In intravascular hemolysis; free hemoglobin will be released into circulation and hence haptoglobin will bind the hemoglobin.

Question 2

In what settings do we see high levels of lactate dehydrogenase?

Answer 2

In intravascular and extravascular hemolysis.

Question 3

What are three causes of intravascular hemolysis?

Answer 3

1. Paroxysmal nocturnal hemoglobinuria.
2. Autoimmune hemolytic anemia.
3. Mechanical destruction.

Question 4

What five diseases can cause extravascular hemolysis?

Answer 4

1. Hereditary spherocytosis
2. G6PD deficiency
3. Pyruvate kinase deficiency
4. Sickle cell disease
5. Hemoglobin C disease

Question 5

What is the pathophysiology of Hereditary spherocytosis?

Answer 5

Intrinsic defects in erythrocyte membrane proteins result in RBC cytoskeletal instability. The proteins Ankyrin and Spectrin are altered in this disease.

Question 6

What is haptoglobin?

Answer 6

Abbreviated as Hp, is a protein. In blood plasma, haptoglobin binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system (mostly the spleen).

Question 7

What does spectrin do?

Answer 7

It is the protein found in the RBC that gives it its biconcave shape, allowing flexibility to the RBC. When it is affected, the RBCs turn into sphere shape without central palor.

Question 8

What do sphere RBCs contain more than regular RBCs?

Answer 8

They have higher MCHC and RDW(mean corpuscular hemoglobin concetration, red cell distribution width), because they can fit more hemoglobin in a sphere than a biconcave disc. It has higher RDW because there is more variability in size of RBCs across the board.

Question 9

Why is there splenomegaly in hereditary spherocytosis?

Answer 9

Because the spleen recognizes that these altered RBCs are not natural, and it works overtime.

Question 10

What organism would cause an aplastic crises in patients with hereditary spherocytosis?

Answer 10

Parvovirus B19 which suppresses the bone marrow.

Question 11

What is the diagnosis test for hereditary spherocytosis?

Answer 11

Osmotic fragility test; RBCs are put in an hypoosmotic solution which would make them lyse more readily than normal RBCs.

Question 12

What is the treatment for hereditary spherocytosis?

Answer 12

Splenectomy.

Question 13

What are Howell-Jolly bodies and why are they seen post-splenectomy?

Answer 13

They are basophilic densities in the red cells which are normally removed by the spleen. They are nuclear remnants (clusters of DNA).

Question 14

What is G6PD deficiency?

Answer 14

They are patients with glucose-6-phosphate dehydrogenase deficiency which is exacerbated by administration of oxidant drugs (primaquine, dapsone, quinidine), sulfa drugs, Fava beans and infections. This disease causes Heinz bodies, leading to bite cells.

Question 15

What are Heinz bodies? And why does this lead to bite cells?

Answer 15

G6PD deficient red cells in combination with high levels of oxidants causes a cross-linking of sulfhydryl groups on globin chains which causes a denaturing and formation of Heinz bodies, which are clumps of hemoglobin, and then the macrophages will remove the Heinz bodies, leaving with bite cells.

Question 16

Why does pyruvate deficiency cause intrinsic hemolysis?

Answer 16

Because the RBCs cannot generate ATP, which means that it can’t maintain the Na/K ATPase, leading to swelling and hemolysis of the red cells.

Question 17

What is the cause of Paroxysmal nocturnal hemoglobinuria?

Answer 17

It is missing CD55 and CD59, so the complement system attacks the red cells.

Question 18

What is the classical test to diagnose Paroxysmal nocturnal hemoglobinuria?

Answer 18

Ham’s test.

Question 19

What is the cause of sickle cell disease?

Answer 19

A single amino acid replacement of valine is being used instead of glutamic acid at position six.

Question 20

What are two triggers for sickle cell patients to have a sickle crisis?

Answer 20

Dehydration and low oxygen tension (in high altitudes).

Question 21

What is the difference between sickle trait and sickle disease?

Answer 21

Sickle trait is when you are heterozygous and sickle disease is when you are homozygous for the disease.

Question 22

What are six complications of sickle cell disease?

Answer 22

1. Sequestration crisis
2. Autosplenectomy
3. Salmonella osteomyelitis
4. Aplastic crises due to Parvovirus B19
5. Pain crises due to vaso-occlusion
6. Renal papillary necrosis due to hypoxemia in the kidneys.

Question 23

What are the treatments for sickle cell disease?

Answer 23

1. Hydroxyurea

2. Bone marrow transplantation

Question 24

What is the cause of hemoglobin C disease?

Answer 24

Similar to sickle cell, but has lysine substituting glutamic acid instead of valine like in sickle cell.

Question 25

How do RBCs look like in people with hemoglobin C disease?

Answer 25

RBCs with little hexagonal crystals within the RBC.

Question 26

What is the clinical presentation for a heterozygous with Hemoglobin C disease? For homozygous?

Answer 26

1. Heterozygous: Asymptomatic

2. Homozygous: Mild hemolysis and splenomegaly.

Question 27

What is SC disease and what is its clinical presentation?

Answer 27

When there is a heterozygous with one hemoglobin C mutation and the other with hemoglobin S mutation. It has a presentation of being a milder form of sickle cell disease.

Question 28

What is the cause of warm agglutinin hemolytic anemia and in what 3 pathologies do we see this?

Answer 28

Warm agglutinins are IgG anitbodies that attach to the red cells and causes them to clump together (agglutinate).

1. Virus (HIV, etc)
2. Lupus
3. Malignancies
4. Drugs
5. Congenital immune abdnormalities

Question 29

What is the cause of cold agglutinin hemolytic anemia and in what 3 pathologies do we see this?

Answer 29

Are IgM antibodies and they also cause the red cells to clump together by IgM binding to RBC antigen which causes complement fixation that leads to MAC (membrane attack complex) lysis. However, they only do so when the body is at low temperatures.

1. CLL
2. Mycoplasma infections
3. Infectious mononucleosis (Epstein Barr virus)

Question 30

What is a positive Coombs’ test?

Answer 30

RBC agglutination with the addition of antihuman antibody because RBCs are coated with immunoglobulin or complement proteins.