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MEH > Session 5: Haemolytic Anaemias and Haemoglobinopathies > Flashcards

Session 5: Haemolytic Anaemias and Haemoglobinopathies Flashcards

1
Q

What is haemolysis?

A

The result of abnormal breakdown of red blood cells.

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2
Q

Haemolysis is divided into two subgroups depending on where the haemolysis occur. What are their names and where is the breakdown occurring?

A

Intravascular haemolysis where the breakdown of the red blood cells occur within the blood vessels.

Extravascular haemolysis where the breakdown occur either in the spleen or in the wider RES.

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3
Q

What is the normal life span of red blood cells?

A

120 days.

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4
Q

The bone marrow can compensate for a decreased life span of red blood cells to a certain degree. It can increase in the rate of production up to how much?
What happens if the rate of destruction exceeds this production limit?

A

Up to six times its normal rate of production.

If rate of destruction exceeds this anaemia will develop.

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5
Q

Define anaemia.

A

A decrease of the total number of red blood cells, haemoglobin, or a lowered ability to carry oxygen.

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6
Q

What are symptoms of haemolytic anaemias?

A

Shortness of breath
Fatigue

Long term:
Jaundice
Splenomegaly
Gall stones

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7
Q
  1. What is a cause of massive sudden haemolysis?

2. What is a consequence of it?

A
  1. Incompatible blood transfusion.

2. Cardiac arrest.

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8
Q

Why would cardiac arrest develop from massive sudden haemolysis?

A

Due to a lack of oxygen delivery to the tissue and hyperkalaemia which develops due to the potassium content in the destroyed red blood cells leaking out into the blood.

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9
Q

There are two main groups of haemolytic anaemias. Which?

A
  1. Inherited due to a defective gene

2. Acquired due to damage of cells

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10
Q

Give examples of inherited haemolytic anaemias and briefly explain them.

A

Glycolysis defect - Pyruvate kinase deficiency limits ATP production

G6PDH deficiency leading to oxidative damage

Defect to membrane proteins such as hereditary spherocytosis

Haemoglobin defect such as sickle cell.

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11
Q

Give examples of acquired haemolytic anaemias and give examples or explain.

A

Mechanical damage - microangiopathic anaemia

Antibody damage - autoimmune haemolytic anaemia

Oxidant damage - exposure to chemicals or oxidants

Heat damage

Enzymatic damage such as snake venom

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12
Q

Give three examples of haemolytic anaemias due to membrane protein defects-

A

Hereditary spherocytosis
Hereditary elliptocytosis
Hereditary pyropoikilocytosis

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13
Q

Explain microangiopathic haemolytic anaemia.

A

Group of acquired anaemias where RBCs are damaged by physical trauma.
This can happen as red blood cells try to squeeze through a narrow passage as in small blood vessels.

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14
Q

Give reasons of why microangiopathic haemolytic anaemia might occur.

A

As we already covered it can happen as red blood cells try to squeeze through a narrow passage. This narrow passage is usually pathological such as in:

Disseminated intravascular coagulation

Thrombotic thrombocytopenic purpura

Defective heart valves or other valves in the circulatory system.

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15
Q

Explain disseminated intravascular coagulation briefly.

A

Condition where bleeding and clotting occur at the same time in the patient.

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16
Q

Explain thrombotic thrombocytopenic purpura and explain why this can cause MAHA.

A

Syndrome where small thrombi form within microvasculature. These small thrombi can cause damage and shearing of red blood cells as the thrombi travel throughout the body.

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17
Q

Explain why defective heart/vessel valves can cause MAHA.

A

For example aortic valve stenosis can cause shearing of red blood cells as the pressure is high in the ventricle and red blood cells want to squeeze through quickly.

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18
Q

What are schistocytes?

A

The resulting red blood cell fragments from MAHAs.

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19
Q

Briefly explain what autoimmune haemolytic anaemia is.

A

A condition where autoantibodies from the patient’s own B lymphocytes bind to the red cell membrane proteins.
This causes the spleen to see the red blood cell that got the antibodies bound to them as abnormal and will therefore remove the red blood cells.

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20
Q

What are some causes of autoimmune haemolytic anaemia?

A

Infection, lymphoproliferative disorders such as leukaemia or lymphoma and also reaction to drugs.

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21
Q

There are two ways to classify autoimmune haemolytic anaemias. Which?

A

Warm where the IgG is maximally active at 37 celsius

Cold where the IgM is maximally active at 4 celsius

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22
Q

Where do IgM autoantibodies bind to red blood cells best?

A

In distal parts of the body such as the fingertips where the temperature is colder. This worsens as well if the patient goes out in cold weather.

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23
Q

Give some key laboratory features to look for in haemolytic anaemias.

A

Increased reticulocyte count
Increase bilirubin
Raised LDH

24
Q

Briefly explain why G6PDH deficiency can cause anaemia.

A

Pentose phosphate pathway produces NADPH.
NADPH is used to produce glutathione which is used to protect against ROS.
Pentose phosphate pathway is the only source of reduced glutathione in red blood cells.
This makes red blood cells susceptible to oxidative stress in case of e.g. infection, drugs or broad beans.
Lipid peroxidation follow as well as protein damage causing aggregates of cross linked haemoglobin (Heinz bodies)

Haemolysis follows the defective red blood cells.

25
Q

Explain how pyruvate kinase deficiency can cause anaemia.

A

Glycolysis pathway is only way red blood cells can produce ATP as they lack mitochondria.
If pyruvate kinase is deficient RBCs can’t produce ATP for e.g. Na/K ATPase to work. The RBCs will think and be destroyed.

26
Q

What mode of inheritance does hereditary spherocytosis follow?

A

Autosomal dominant

27
Q

If there is no family history of HS how can it be acquired?

A

By spontaneous mutation

28
Q

In HS there is a gene mutation in proteins in the cell membrane. Which are the four most common?
Which is the most common of the four?

A

Ankyrin
Spectrin
Band 3
Protein 4.2

Ankyrin is the most common one.

29
Q

What is the common functional role of these four proteins in red blood cells?

A

They link the plasma membrane with the cytoskeleton.

A disruption can cause the cell to become sphere-shaped.

30
Q

Why might red blood cells with a spherocyte shape function less efficiently than normally shaped red blood cells?

A

Because they are less flexible than normal RBCs they might not reach the tissue that requires it. They also have a smaller surface area.

Also they can become trapped and damaged as they pass through the spleen which means the spleen will destroy the RBCs.

31
Q

Why would a patient with HS have an enlarged spleen?

A

Due to a higher activity of haemolysis.

32
Q

Why is the reticulocyte count above the normal range in a patient with HS?

A

Because haemopoiesis will increase in both spleen and in bone marrow to compensate for the increased haemolysis.

33
Q

Why might a patient with HS have a lower platelet count?

A

Due to splenomegaly. Enlarged spleen means that the blood will spend more time in the spleen and therefore thrombocytes can pool there. This doesn’t mean that there are less platelets, just less platelets in the circulatory system.

34
Q

Give four complications that can occur in patients with HS.

A 
Mild anaemia
Splenomegaly
Jaundice
Howell-Jolly bodies
Lower platelet count
They might be immunocompromised
35
Q

If you have a severe symptomatic HS, how can it be treated?

A

By folic acid and hydroxycarbamide

Surgically by splenectomy.

36
Q

Why would a patient without a spleen be more susceptible to N meningitidis? What other infections might the patient be at risk of?

A

Because the spleen is removed the patient is immunocompromised.
The spleen is good at dealing with bacteria that has a capsule. This means that any bacterial infection from a bacteria with a capsule will not be dealt with as efficiently and the patient will hence be more susceptible to those types of infection.

37
Q

What are haemoglobinpathies?

A

Inherited disorders where expression of one or more of the globin chains of haemoglobin is abnormal.

38
Q

Which are the two main categories of haemoglobinpathies? What is the difference between them?

A

Abnormal haemoglobin variants
Thalassemias.

AHVs: synthesis of an abnormal haemoglobin

Thalassemias: reduced rate of synthesis of normal alpha or beta globin chains.

39
Q

Give an example of an abnormal haemoglobin variant.

A

Sickle cell disease

40
Q

Explain which genes are involved in thalassemia and how the condition arises.

A

Abnormal expression of alpha globin genes on chromosome 16 or beta globin genes on chromosome 11.
A normal expression would result in a 1:1 ratio of alpha to non-alpha globin chains.
Abnormal expression can result in abnormalities in the relative and absolute amounts of globin chains.

41
Q

Briefly outline what happens to red blood cells as a result of thalassemia.

A

A low level of intracellular haemoglobin which will cause hypochromic and microcytic red blood cells.
The relative excess of the other globin chain aggregates and causes damage to the red cell membrane.
Most of maturing erythroblasts are destroyed in bone marrow and increased haemolysis of RBCs occur in the spleen. This causes haemolytic anaemia.

42
Q

What two main groups of thalassemia are there?

A

Alpha-thalassemia

Beta-thalassemia

43
Q

What are the different alpha-thalassemias? Explain the complications.

A
  1. Silent carrier - deletion of a single alpha-globin gene which is asymptomatic
  2. Alpha-thalassemia trait where there is deletion of two alpha-globin genes. Minimal or no anaemia. Can be some microcytosis and hypochromia.
  3. Haemoglobin H (HbH) disease. Deletion of three alpha-globin genes. Moderately severe anaemia. Microcytosis, hypochromia and anaemia with target cells and Heinz bodies.
  4. Hydrops fetalis. Deletion of all four alpha-glboin genes. Excess of gamma-globin chains in foetus forming tetramers (Hb Bart) which will be unable to deliver oxygen to tissues. Usually causes intrauterine death.
44
Q

What are the different beta-thalassemias? Explain the complications.

A

B-thalassemia major - Severe transfusion dependent anaemia manifesting first at around 6 to 9 months after birth.

B-thalassemia minor (trait) - usually asymptomatic with a mild anaemia however very microcytic and hypochromic. Heterozygotic.

45
Q

Iron deficiency and B-thalassemia minor can look very similar. What is the major difference?

A

That in thalassemia trait there is usually a normal haemoglobin production where as this is not the case in iron deficiency.

46
Q

What are the main consequences of thalassemia?

A

Due to the anaemia there will be extramedullary haemopoiesis as compensation. This can result in splenomegaly, hepatomegaly and expansion of haemopoiesis into bone cortex in order to ensure the RBC requirement is met. This will impair growth and cause skeletal abnormalities.

There will also be reduced O2 delivery resulting in increased EPO which will further contribute to the drive of making more defective red cells.

The enlarged spleen means that red blood cells will spend more time in the spleen and further be broken down.

47
Q

What is the major cause of premature death in thalassemias and why?

A

Iron overload.
This is because the body will excessively absorb dietary iron due to ineffective haemopoiesis which will go into Fenton reaction and cause oxidative damage.
Also the repeated blood transfusions will be harmful in the long term.

48
Q

How do you treat thalassemia?

A 
Transfusion
Iron chelation
Folic acid
Immunisation as the immune system can be compromised
Stem cell transplantation
49
Q

Explain how sickle cell disease arises.

A

Inheritance of sickle beta-globin chain.

This is caused by a point mutation - substitution of valine for glutamic acid in position 6 in the b-chain.

50
Q

Which is the most common severe sickle cell anaemia?

A

HbSS (homozygous sickle cell anaemia)

51
Q

Give an example of a mild asymptomatic sickle cell anaemia which can be beneficial and why it is benificial.

A

HbS carrier state which protects against malaria.

52
Q

Why is HbS carrier state sickle cell anaemia usually mild?

A

Because the HbS readily give up oxygen in comparison to HbA.

53
Q

Why would sickle cell disease become a problem?

A

In low oxygen state the deoxygenated HbS forms polymers (aggregates) and the red cells will become sickle shaped. This shape is irreversible cannot deform and can cause aggregations in small blood vessels as they become sticky.

54
Q

What are the major consequences of sickle cell formation?

A 
Vaso-occlusive episodes
Anaemia - shortened life span
Jaundice - increased bilirubin and gall stones
Splenic atrophy
Kidney failure
Tissue hypoxia
55
Q

Explain vaso-occlusive episodes.

A

Pain and syndromes such as stroke or acute chest syndrome. Also chronic kidney disease and joint damage from avascular necrosis.
Painful bone crises as well.
This is all due to occlusion of small capillaries where the sickle shaped RBCs become trapped.
This can eventually lead to end organ damage due to chronic or acute thromboses.

56
Q

Explain splenic atrophy.

A

Compromised immune system occurs due to splenomegaly and defective spleen. This makes the patient more susceptible to functions by encapsulated bacteria such as streptococcus pneumoniae and Neisseria Meningitidis

MEH (22 decks)

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