Haematology - haemolytic anaemia

Question 1

What are the causes of haemolytic anaemia?

Answer 1

Inherited haemolytic anaemias:

• Hereditary spherocytosis
• Hereditary elliptocytosis
• Thalassemia
• Sickle cell anaemia
• G6PD deficiency

Acquired haemolytic anaemias:

• Autoimmune haemolytic anaemia
• Alloimmune haemolytic anaemia (transfusions reactions and haemolytic disease of newborn)
• Paroxysmal nocturnal haemoglobinuria
• Microangiopathic haemolytic anaemia
• Prosthetic valve related haemolysis

Question 2

Features of haemolytic anaemia

Answer 2

Anaemia due to the reduction in circulating RBCs

Splenomegaly - spleen becomes filled with destroyed red blood cells

Jaundice - bilirubin released during breakdown of RBCs

Question 3

Investigations in suspected haemolytic anaemia

Answer 3

Full blood count shows a normocytic anaemia

Blood film shows schistocytes (fragments of red blood cells)

Direct Coombs test is positive in autoimmune haemolytic anaemia

Reticulocyte count will often be raised due to high RBC turnover

Question 4

What is hereditary spherocytosis?

Answer 4

Most common inherited haemolytic anaemia in northern Europeans

Autosomal dominant

Sphere shaped RBCs that are fragile and easily break down

Question 5

How does hereditary spherocytosis present?

Answer 5

Jaundice

Gallstones

Splenomegaly

Aplastic crisis in the presence of parvovirus

Question 6

Treatment of hereditary spherocytosis?

Answer 6

Folate supplementation and splenectomy.

Cholecystectomy may be required if gallstones are a problem.

Question 7

What is G6PD deficiency?

Answer 7

Defect in the red blood cell enzyme G6PD

More common in Mediterranean and African people

X linked recessive

Question 8

What things can trigger G6PD crises?

Answer 8

Infections

Medications e.g. primaquine (antimalarial), ciprofloxacin, sulphonylureas, sulfasalazine and other sulphonamide drugs

Fava beans (broad beans).

Question 9

How does G6PD deficiency typically present?

Answer 9

Jaundice (usually in neonatal period)

Gallstones

Anaemia

Splenomegaly

Heinz bodies on blood film

Question 10

How can G6PD deficiency be diagnosed?

Answer 10

G6PD enzyme assay

Question 11

What are the two types of autoimmune haemolytic anaemias?

Answer 11

Warm (more common)

Cold

Question 12

How does warm autoimmune haemolytic anaemia occur?

Answer 12

Haemolysis occurs at normal or above normal temperatures.

It is usually idiopathic, meaning that it arises without a clear cause.

Question 13

How does cold autoimmune haemolytic anaemia occur?

Answer 13

At lower temperatures (e.g. less than 10ºC) the antibodies against red blood cells attach themselves to the red blood cells and cause agglutination of RBCs

The agglutination results in RBC destruction

This type is often secondary to other conditions

Question 14

What can cold autoimmune haemolytic anaemia be secondary to?

Answer 14

Lymphoma

Leukaemia

SLE

Infections e.g. mycoplasma, EBV, CMV, HIV

Question 15

Management of autoimmune haemolytic anaemias?

Answer 15

Blood transfusions

Prednisolone (steroids)

Rituximab (a monoclonal antibody against B cells)

Splenectomy

Question 16

What is alloimmune haemolytic anaemia

Answer 16

Either foreign RBCs or foreign antibody against own RBCs in blood

E.g. transfusion reactions, haemolytic disease of new-born

Transfusion reaction - immune system produces antibodies against antigens on those foreign red blood cells. This creates an immune response that leads to the destruction of those red blood cells.

Question 17

What is paroxysmal nocturnal haemoglobinuria?

Answer 17

Genetic mutation in haematopoietic stem cells in bone marrow

The mutation results in a loss of the proteins on the surface of red blood cells that inhibit the complement cascade.

The loss of protection against the complement system results in activation of the complement cascade on the surface of red blood cells and destruction of the red blood cells.

Question 18

Presentation of paroxysmal nocturnal haemoglobinuria

Answer 18

Red urine in the morning (containing Hb and haemosiderin)

Patients are also predisposed to thrombosis e.g. DVT/PE and smooth muscle dystonia e.g. oesophageal spasm and erectile dysfunction

Question 19

Management of paroxysmal nocturnal haemoglobinuria

Answer 19

Eculizamab - monoclonal antibody that targets complement component 5 (C5) causing suppression of the complement system

Or bone marrow transplant (can be curative)

Question 20

What is microangiopathic haemolytic anaemia (MAHA)?

Answer 20

Small blood vessels have structural abnormalities causing haemolysis of blood travelling through

Usually secondary to an underlying condition e.g.:

• HUS (haemolytic uraemic syndrome)
• DIC
• Thrombotic Thrombocytopenia Purpura (TTP)
• Systemic Lupus Erythematosus (SLE)
• Cancer

Question 21

What is prosthetic valve haemolysis?

Answer 21

A key complication of prosthetic heart valves.

Turbulence around valve causes haemolysis

Question 22

Management of prosthetic valve haemolysis

Answer 22

Monitoring

Oral iron

Blood transfusion if severe

Revision surgery may be required in severe cases