Haemolytic Anaemia

Question 1

.. refers to the destruction of red blood cells (RBCs), which is broadly defined as a reduction in the life span below 100 days (normal 110-120 days).

Answer 1

Haemolysis refers to the destruction of red blood cells (RBCs), which is broadly defined as a reduction in the life span below 100 days (normal 110-120 days).

Question 2

Haemolytic anaemia

Answer 2

Haemolytic anaemia is defined as anaemia secondary to reduced survival of RBCs. They have a varied aetiology, as is the clinical presentation; together they represent approximately 5% of all anaemias.

Regardless of the underlying cause, if erythropoiesis within the bone marrow cannot keep pace with the destruction of RBCs anaemia will ensue. Mild haemolysis may be completely asymptomatic whereas severe, acute haemolysis will lead to cardiopulmonary decompensation.

Question 3

Haemolytic anaemia can be classified as inherited or aquired.

Answer 3

Haemolytic anaemia can be classified as inherited or aquired.

Question 4

Symptoms

Haemolytic anaemia

Answer 4

Fatigue
Weakness
Paraesthesia
Dyspnoea
Gastrointestinal symptoms (e.g. nausea, dyspepsia)
Weight loss

Question 5

Signs

Haemolytic anaemia

Answer 5

Atrophic glossitis
Pallor
Fever
Splenomegaly
Evidence of underlying disease

Question 6

Haemolysis

Answer 6

Jaundice
Abdominal pain (e.g. gallstones)
Dark urine (e.g. haemoglobinuria secondary to intravascular haemolysis)

Question 7

Diagnostic work-up for patients with suspected haemolytic anaemia should begin with a haemolytic screen.
The haemolytic screen includes a standard set of blood tests that help to confirm the presence of haemolysis and may suggest an underlying diagnosis. A standard haemolytic screen consists of:

Answer 7

FBC (inc. reticulocyte count)
Blood film
LDH
LFTs (bilirubin)
Serum haptoglobin
Additional tests

Question 8

The full blood count is essential to diagnose anaemia and provide evidence of other parameters such as white blood cell and platelet counts.

Using the mean corpuscular volume (MCV), we may delineate the cause of anaemia based on the morphology of the red blood cells (macro-, normo- and microcytic). Haemolytic anaemia is traditionally causes as a …

Answer 8

The full blood count is essential to diagnose anaemia and provide evidence of other parameters such as white blood cell and platelet counts.

Using the mean corpuscular volume (MCV), we may delineate the cause of anaemia based on the morphology of the red blood cells (macro-, normo- and microcytic). Haemolytic anaemia is traditionally causes as a normocytic anaemia.

Question 9

The peripheral blood film is important to assess the morphological characteristics of erythrocytes and can detect concomitant abnormalities such as haematological malignancies.

Typical erythrocyte morphologies associated with haemolysis may include:

Answer 9

Spherocytes (e.g. hereditary spherocytosis)
Schistocytes (e.g. microangiopathic haemolytic anaemia)
Sickle cells (e.g. sickle cell disease)

Question 10

Lactate dehydrogenase (LDH) is a non-specific marker of cell damage and turnover. LDH is sensitive for the presence of …, but it is a not specific.

Answer 10

Lactate dehydrogenase (LDH) is a non-specific marker of cell damage and turnover. LDH is sensitive for the presence of haemolysis, but it is a not specific.

Question 11

Liver function tests (LFTs) are essential to assess the level of bilirubin. In haemolysis there is an … production of bilirubin (a breakdown product of haemoglobin).

Answer 11

Liver function tests (LFTs) are essential to assess the level of bilirubin. In haemolysis there is an increased production of bilirubin (a breakdown product of haemoglobin). If the liver is unable to completely compensate (by conjugating and excreting the bilirubin) a mild unconjugated hyperbilirubinaemia may be seen.

Question 12

… is a plasma protein, which binds to free haemoglobin within the blood. In the presence of intravascular haemolysis, free haemoglobin is mopped up by haptoglobin. The haemoglobin-haptoglobin complex is removed by the liver leading to a decrease in the level of haptoglobin. Importantly, haptoglobin is an acute phase reactant and as such levels my be raised despite significant haemolysis.

Answer 12

Haptoglobin is a plasma protein, which binds to free haemoglobin within the blood. In the presence of intravascular haemolysis, free haemoglobin is mopped up by haptoglobin. The haemoglobin-haptoglobin complex is removed by the liver leading to a decrease in the level of haptoglobin. Importantly, haptoglobin is an acute phase reactant and as such levels my be raised despite significant haemolysis.

Question 13

Patients with hereditary spherocytosis are usually unaffected, but if treatment is required, it typically involves a … that dramatically increases the red blood cell count.

Answer 13

Patients with hereditary spherocytosis are usually unaffected, but if treatment is required, it typically involves a splenectomy that dramatically increases the red blood cell count.

Question 14

Defects in the metabolic apparatus can predispose RBCs to oxidative damage. One of the most common causes worldwide is …

Answer 14

Defects in the metabolic apparatus can predispose RBCs to oxidative damage. One of the most common causes worldwide is glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency). This is an X-linked recessive disorder, which may lead to episodes of haemolysis in the presence of oxidative stressors.

Question 15

Inherited defects in these important genetic regions can lead to alteration in the composition of haemoglobin, which can have an effect on membrane stability and erythrocyte survival. Important conditions include:

Answer 15

Sickle cell disease is an autosomal recessive disease that occurs due to a point mutation within the beta-globin gene. The resultant haemoglobin (HbS) is 50x less soluble than HbA and is at risk of polymerising under low-oxygen tension, which further damages the RBC.
Alpha-thalassaemia and beta-thalassaemia are characterised by a genetic deficiency of alpha and beta-globin chains, respectively. Both conditions are characterised by the absent or reduced production of normal globin chains leading to an imbalance in chain production, abnormal erythropoiesis and defective erythrocytes.

Question 16

Antibodies that bind to the erythrocyte membrane may be alloantibodies or autoantibodies.

Answer 16

Alloantibodies are antibodies produced by one individual that will react with antigens of another individual of the same species. May be seen in haemolytic transfusion reactions and haemolytic disease of the newborn.
Autoantibodies, which are generated against components of the individuals own tissue, may be seen in AIHA. AIHA is further divided depending on the type of autoantibody present being ‘warm’ or ‘cold’.

Question 17

Warm AIHA vs Cold AIHA

Answer 17

Warm AIHA is associated with an antibody reaction against erythrocytes at higher temperatures (e.g. > 37°), which then leads to agglutination. Warm AIHA may be idiopathic, or associated with immune dysfunction secondary to infection, chronic inflammation or malignancy. Warm AIHA may be associated with infections such as HIV and EBV, inflammatory disorders such as SLE, or malignancies such as chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma.

Cold AIHA is associated with a reaction against erythrocytes at lower temperatures (e.g. < 32°), which then leads to agglutination. Cold AIHA may be idiopathic or associated with systemic diseases such as lymphoma, Mycoplasma pneumoniae infection and infectious mononucleosis.

Question 18

Non-immune mediated destruction of erythrocytes can occur due to a number of different mechanisms.

Answer 18

Mechanical trauma - due to heart and large blood vessel pathology (e.g. prostheses).
Microangiopathic haemolytic anaemia (e.g. HUS, TTP, DIC).
Burns
Infections
Drugs & chemicals
Hypersplenism

Question 19

Finally, .. is a term .that refers to the reduction in RBCs, platelets and granulocytes in association with splenomegaly, regardless of cause.

Answer 19

Finally, hypersplenism is a term that refers to the reduction in RBCs, platelets and granulocytes in association with splenomegaly, regardless of cause.