What is Sickle Cell Disease (SCD)?
Sickle Cell Disease is a type of haemoglobinopathy. Haemoglobinopathies is the collective term used to describe inherited genetic disorders affecting the structure or formation of haemoglobin.
Haemoglobinopathies are caused by point mutations which result in amino acid substitutions and ultimately a change in the alpha or beta globin chain of haemoglobin. In sickle cell disease, glutamic acid is replaced by a valine amino acid in the beta globin chains at position 6. This results in the formation of HbS. HbS distorts the structure of red blood cells, giving them a sickle shape.(1)
Common types of Sickle Cell Disease
Epidemiology
The gene is common in the African, Middle Eastern, Indian, Carribean and Mediterranean populations. The most common form of SCD is the sickle cell trait form (heterozygous carriers). Carriers are believed to have some protection against falciparum malaria. They tend to be asymptomatic and sickling occurs only under severe hypoxic (or dehydration) conditions in this population.
Clinical Features of SCD
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Chronic haemolytic anaemia
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The sickle shape of red blood cells make them more prone to intravascular haemolysis, which leads to anaemia. The increased breakdown of red blood cells increases bilirubin levels, which can cause jaundice. Chronic haemolysis and hyperbilirubinemia is associated with formation of bile stones can lead to cholecystitis.(1)
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Vaso-occlusion
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Blockage of vessels by the sickle cells obstructs blood and oxygen delivery to the tissues, thereby causing tissue ischaemia. In the acute setting, this can present as severe pain, typically in the chest, abdomen and long bones. This is known as sickle cell crisis.
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Repeated episodes of vaso-occlision can result in avascular necrosis of the femoral/humeral head, and chronic leg ulcers.(1)
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Hyposplenism
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Blockage of the splenic vessels by sickle cells leads to infarction, and reduced splenic function. As the spleen helps clear encapsulated bacteria, patients with hyposplenism are at increased risk of infections with encapsulated bacteria e.g. haemophilus influenza, neisseria meningitidis, streptococcus pneumoniae.(1)
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Priapism
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Priapism is sustained (more than 3 hours), painful erection, and occurs due to obstruction of normal blood flow within the penis. (1)
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This is a medical emergency.
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Aplastic crisis
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Parvovirus B19 infects red blood cell progenitors and impairs cell division, so the bone marrow is not able to produce more red blood cells. For healthy individuals, this may not cause any problems, however in sickle cell patients, this is a medical emergency. This is because the life span of their red blood cells is already reduced due to the sickle cell disease. The additional drop in production of red blood cells as a result of this virus will cause severe anaemia that may require blood transfusion. (1)
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Investigations and Diagnosis of SCD
Antenatal Diagnosis
All pregnant women in the UK are offered screening for sickle cell disease. This involves a blood test to determine if the pregnant woman is a carrier of the disease, or has the disease. If they are found to be a carrier, the father of the child may be offered screening for carrier status. If the father declines, or is not available for consent, antenatal diagnostic testing is offered. It is also offered if both the mother and father are tested and found to be carriers of sickle cell disease.(3) Click here to see the pathway for antenatal screening in the UK.
There are 2 main ways antenatal diagnosis can be achieved, and the method performed is based on the gestation of the foetus.
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Chorionic Villus sampling: >11 weeks of pregnancy
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Amniocentesis: 15-16 weeks of pregnancy(3)
Neonatal Screening
A heel prick test routinely done as part of the neonatal bloodspot screening programme in England aims to diagnose SCD soon after birth. There are numerous laboratory tests used to detect the presence of haemoglobin. Examples of these tests include haemoglobin electrophoresis or high performance liquid chromatography.(3)
Full Blood Count
FBC may reveal anaemia.
Blood Film
The peripheral blood film will show sickle shaped red blood cells.
Some patients may have Howell-Jolly bodies, which are usually removed by the spleen. Since sickle cell patients may have hyposplenism, these inclusions remain in the red blood cells.(1)
Sickle shaped red blood cell:
(Image source: Servier Medical Art; license: https://creativecommons.org/licenses/by/3.0/legalcode)
Management of SCD
Patient Advice
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knowing individual patient's triggers (ex. dehydration, infection)(1,2)
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maintaining hydration
Supportive Care
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Red blood cell transfusions may be required in periods of severe anaemia
Acute Sickle Crisis
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Admit to hospital
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Analgesia - paracetamol, ibuprofen, codeine (if paracetamol and ibuprofen do not settle pain)(2)
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IV hydration
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Oxygen
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If fever is present, do blood and urine cultures, and a chest X-ray(1)
Prevention of Crises
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Hydroxycarbamide - anti-metabolite drug which works by increasing the amount of fetal hemoglobin. (1)
Prevention of Infection
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Penicillin prophylaxis against encapsulated bacteria
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Vaccinations: pneumococcal, H.influenzae, and Meningococcal
Currently, the only method of eliminating SCD is through haematopoietic stem cell transplantation. However, prophylactic treatment such as Hydroxycarbamide is more widely used to reduce occurrence of severe pain episodes and reduce risk of severe complications in the future.(1)
References
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Mehta AB, Hoffbrand AV. Haematology at a Glance. 4th ed.: John Wiley & Sons; 2014.
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NICE CKS. Sickle cell disease. 2016; Available at: https://cks.nice.org.uk/sickle-cell-disease#!topicSummary
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Public Health England. Sickle cell and thalassaemia (SCT) screening: antenatal care pathway. Public Health England 2015.
