Haemolytic Anaemias

Question 1

Define haemolytic anaemia

Answer 1

Haemolytic anaemia is a group of disorders characterised by premature destruction of red blood cells (RBCs) and a shortened RBC lifespan

Under normal circumstances, RBCs have a lifespan of approximately 120 days. In haemolytic anaemia, this lifespan is significantly reduced, leading to an increased turnover of RBCs

This accelerated destruction of RBCs can occur within the blood vessels (intravascular haemolysis) or in the spleen or liver (extravascular haemolysis)

haemolysis leads to the release of haemoglobin from the RBCs into the plasma

The bone marrow tries to compensate for the loss of RBCs by increasing the production of new RBCs (erythropoiesis), often leading to an increased number of immature RBCs, or reticulocytes, in the blood

Haemolytic anaemia can result from various causes, which can generally be divided into two categories: intrinsic and extrinsic

Intrinsic causes refer to defects in the RBCs themselves, such as in certain genetic conditions (like sickle cell anaemia or thalassemia) or enzyme deficiencies (like glucose-6-phosphate dehydrogenase deficiency)

Extrinsic causes are conditions outside the RBCs that lead to their destruction, such as autoimmune disorders, infections, certain drugs, or mechanical damage (for example, from artificial heart valves)

Question 2

Describe clinical & laboratory features of haemolysis

Answer 2

Clinical Features:

1. Fatigue, weakness, and paleness: These are common symptoms of anaemia caused by a lack of red blood cells.
2. Jaundice: This is a yellowish discolouration of the skin and eyes caused by the buildup of bilirubin, a product of haemoglobin breakdown
3. Dark urine: Hemoglobin released from the destroyed red cells is converted into a form that may darken the urine
4. Spenomagly: An enlarged spleen may result from increased activity to clear the damaged red blood cells

Laboratory Features:

1. Decreased Hemoglobin/Hematocrit: These measurements of red blood cell quantity will be lower due to the destruction of red blood cells
2. Increased Reticulocytes: The body will attempt to create more red blood cells to replace the ones lost, leading to an increased count of these immature red blood cells
3. Increased Bilirubin: This is a product of haemoglobin breakdown, and levels will be high due to the increased destruction of red blood cells
4. Positive Direct Coombs Test: This test is often positive in autoimmune haemolytic anaemia, a condition where the body’s immune system attacks its own red blood cells
5. Increased Lactate Dehydrogenase (LDH): This enzyme, present in red blood cells, will be released into the blood upon hemolysis
6. Haptoglobin: This protein binds free haemoglobin released into the bloodstream. In hemolytic anaemia, haptoglobin levels in the serum will be low because most of it is used up binding a large amount of haemoglobin released from the lysed red cells
7. Peripheral Blood Smear: This may show abnormal red blood cell morphology, such as spherocytes in autoimmune hemolytic anaemia or sickle cells in sickle cell anaemia

Question 3

Explain the causes of haemolysis

Answer 3

1) Intrinsic abnormalities:

• Hereditary spherocytosis: A genetic disorder that leads to defective red blood cell membranes, causing the cells to take on a spherical shape and making them more fragile
• Sickle cell disease: A genetic disorder that results in the production of abnormal hemoglobin (hemoglobin S) which can distort the shape of the red blood cells, especially in low-oxygen conditions
• Thalassemias and other hemoglobinopathies: These are disorders that involve problems with the production of the hemoglobin protein
• Paroxysmal nocturnal hemoglobinuria (PNH): A rare, acquired disorder where the red blood cells are deficient in certain proteins that protect them from the immune system
• G6PD deficiency: This is a genetic disorder that results in a deficiency of an enzyme called glucose-6-phosphate dehydrogenase, which helps to protect the red blood cell from oxidative damage

2) Extrinsic Factors:

• Autoimmune hemolytic anaemia: In this condition, the immune system mistakenly recognises the body’s own red blood cells as foreign and produces antibodies that lead to their destruction
• Drug-induced hemolysis: Certain drugs can cause hemolysis either through immune mechanisms (drug-induced immune hemolytic anemia) or direct damage to the red blood cells (drug-induced nonimmune hemolytic anemia)
• Infections: Certain infectious agents like malaria can invade red blood cells and cause them to lyse
• Mechanical damage: Physical damage can be caused by artificial heart valves or severe hypertension. This is known as microangiopathic or macroangiopathic hemolytic anemia
• Thermal injury or certain types of snake venom can also lead to haemolysis

3) Metabolic causes:

• Liver disease: The liver plays a key role in the production and breakdown of red blood cells. Severe liver disease can lead to haemolysis
• Kidney disease: Certain kidney conditions, like thrombotic thrombocytopenic purpura (TTP), can lead to haemolysis
• Severe burns: These can lead to massive release of inflammatory molecules that can cause haemolysis

Question 4

Describe some of the haemoglobinopathies

Answer 4

Haemoglobinopathies are a group of inherited disorders characterised by abnormal structure or underproduction of haemoglobin

1) Sickle Cell Disease (SCD):

• This disease is caused by a single point mutation in the beta-globin gene, leading to the production of haemoglobin S
• When deoxygenated, this abnormal haemoglobin polymerises and causes the red blood cells to take on a sickle shape
• These sickle cells can cause blockages in small blood vessels leading to painful crises, organ damage and an increased risk of infection

2) Thalassemias:

• Thalassemias are caused by mutations that result in the underproduction of one or more of the globin chains of haemoglobin
• They are broadly classified into alpha and beta-thalassemia
• Alpha-thalassemia is caused by deletions or mutations in the genes that code for the alpha chains, while beta-thalassemia is caused by mutations in the gene that codes for the beta chains
• Both result in an imbalance in globin chain production, leading to ineffective erythropoiesis and anaemia