Sickle Cell Disease

Question 1

What is SCD and how does it arise? Include prevalence

Answer 1

• It is a qualitative haemoglobinopathy that is present globally but prevalent in Africa and the Mediterranean.
• It is the synthesis of structurally abnormal haemoglobin.
• It is normally seen in the second 6 months of life when HbF levels fall and HbA levels rise.
• It is due to a point mutation in the B-globin gene of haemoglobin causing a change from adenine to thymine, meaning that the triplicate coding for glutamine at position 6 is now coding for valine. As glutamine is negatively charged but valine is hydrophobic, this change affects the structure of Hb, as valine sits in a hydrophobic cleft in an opposite Hb chain, causing aggregation of Hb chains and the formation of rigid polymers.
• This is autosomal recessive.
• This type of Hb is known as HbS.

Question 2

When does SCD present and cause symptoms of disease?

Answer 2

• Upon deoxygenation, HbS loses its solubility and it forms long rigid polymers.
• This distorts the RBC shape into a sickle.
• This is reversible, but after numerous cycles, this becomes irreversible.
• These sickle cells have adhesion molecules on their surface, which causes them to bind to endothelial cells, narrowing the lumen and increasing the risk of thrombosis.
• These sickle cells are recognised by the RES and are removed, leading to extravascular haemolytic anaemia.
• This is seen in hypoxia, stress, increased temperature, infection and in acidosis.

Question 3

What are the symptoms and their explanations?

Answer 3

• Carriers of the gene are asymptomatic, but can show a sickling crisis in unfavourable conditions (hypoxia, acidosis, infection).
• Anaemia - this is due to HbS releasing oxygen more readily than HbA, and due to the extravascular haemolysis of the sickled cells.
• Splenomegaly and bone marrow hyperplasia - this is due to the increased removal of sickled cells via RES and the hyper erythropoiesis to counteract this.
• Painful vaso-occlusive crisis - this is due to irreversibly sickled cells blocking blood vessels, leading to tissues becoming hypoxic and ischaemia in the spleen, bones and lungs.
• Stroke - this is due to occlusion occurring in the brain.
• Hand foot syndrome - this is fingers of varying lengths in children. This is due to occlusion in the middle finger.
• Visceral Sequestration Crisis - this is due to pooling of RBCs in the liver, spleen or lungs.
• Aplastic crisis - this is due to folic acid deficiency or parvovirus.
• Haemolytic crisis - this is due to an increased haemolysis and increased reticulocyte production to counteract this.
• Severe lower leg ulcers
• Liver damage
• Kidney damage

Question 4

What are the laboratory findings?

Answer 4

• Microcytic anaemia.
• Increased reticulocyte count.
• Blood film shows sickled cells.

Question 5

What further tests should be carried out to confirm diagnosis?

Answer 5

• HPLC - this is the gold standard to determine the Hb variants present in a patient. If HbS is present, this will be detected, as it has a longer retention time than HbA. This will also show the % of HbS present.
• Hb electrophoresis - this separates the Hb present.
• Sickle Solubility test - this mixes the blood with saponin (to lyse the RBCs) and sodium dithionite (to reduce oxygen tension). If positive, the sample will be a pink turbid solution. (Negative will be clear).

Question 6

What are the types of Hb found in SCD?

Answer 6

• Haemoglobin S.This type of haemoglobin is present in sickle cell disease.
• Haemoglobin D.This type of haemoglobin is present in somesickle cell disorders.

Question 7

How is SCD treated?

Answer 7

• Analgesics and hydration.
• Prophylaxis - avoid triggering factors, dehydration, anoxia, infections, cool temperatures.
• Folic acid.
• Good general nutrition and hygiene.
• If in severe crisis, exchange transfusion and transfusions are given.
• Screening