Sickle Cell Disease

 

Sickle cell disease encompasses a group of inherited conditions that have the inheritance of sickle haemoglobin in common.  Sickle haemoglobin has an abnormal beta-globin chain that causes it to polymerize when deoxygenated, which distorts the erythrocyte into a sickle shape.  The deformed erythrocytes form clusters that block blood vessels; damage large and small blood vessels; are sequestered in the liver and spleen; and cause anaemia (of varying degrees), intense pain (known as sickle cell crisis), infections, and other complications of sickle cell disease

Sickle cell disease is estimated to affect 1 in every 2000 live births in England, and it is now the most common genetic condition at birth.  The highest prevalence of sickle cell disease is among Black African and Black Caribbean people, but cases also occur in families originating from the Middle East, parts of India, the eastern Mediterranean, and South and Central America.  Life expectancy has improved considerably over the last decades, due to improvements in the management of infections and other complications in childhood, new interventions, active health maintenance for adults, and counselling. It is estimated that more than 90% of people of all phenotypes will survive past 20 years of age, and significant numbers are older than 50 years of age

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When to suspect sickle cell disease

Suspect sickle cell disease if a person is in a high-risk group (see summary above) and:

  • Is a child aged 9–18 months with painful dactylitis (painful swelling of the bones of the hands and feet.  There may be chronic shortening of a digit due to epiphyseal damage
  • Has a sudden severe infection
  • Presents with features of an acute crisis, or with a history of features consistent with an acute crisis
  • Presents with features of a chronic complication of sickle cell disease

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Consider discussing haemoglobinopathy status in high-risk groups

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Diagnosis of sickle cell disease

Sickle cell disease is always diagnosed after both an initial and confirmatory test are positive

  • Tests can include full blood count, reticulocyte count, and blood film, together with more specialized laboratory tests to identify haemoglobinopathies

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When to suspect an acute sickle cell crisis

Suspect an acute sickle cell crisis in a person with sickle cell disease who presents with a sudden onset of paininfectionanaemia, or other symptoms, such as a stroke or priapism

  • There is often a history of a previous crisis (or rarely, sickle cell disease may be undiagnosed)
  • Older children and adults are often able to state whether their pain is typical of sickle cell disease

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Assessment of acute crisis

If an acute sickle cell crisis is suspected:

  1. Take a history. Ask about clinical features of the acute complications of sickle cell disease, such as:
    1. Pain in the bones and joints
      1. Painful, swollen joints may be due to acute bone infarction during an acute pain crisis, or septic arthritis
      2. An infant may present with dactylitis (painful swelling of the bones of the hands and feet)
    2. Abdominal pain
      1. Consider the causes of abdominal pain that are common in people with sickle cell disease, as well as general surgical pathology
      2. Consider that pain may be secondary to gallstones (which are very common), ascending cholangitis, acute cholecystitis, gallbladder empyema, or acute pancreatitis
      3. An abdominal sickle crisis is often indistinguishable from an acute abdomen due to a surgical cause
    3. Fever
      1. A crisis may also be associated with an acute febrile illness due to infection
      2. Fever may present alone or may accompany an acute painful crisis with no signs of infection
      3. Children younger than 5 years of age are particularly at risk of pneumococcal infection
    4. Breathlessness
      1. Chest pain and breathlessness occur in acute chest syndrome
    5. Symptoms of a stroke
      1. An acute stroke due to ischaemia may occur at any age but is common in children. The incidence increases with age in adults older than 30 years of age (adults aged 20–29 years are more likely to have a subarachnoid or intracerebral haemorrhage)
      2. Neurological complications  of a sickle cell crisis may also present as hemparesis, speech problems, seizures, or altered consciousness
    6.  Acute renal failure
      1. This may be precipitated by dehydration and sepsis
    7. Acute priapism
      1. Ask about the length of time since the onset
      2. Acute priapism becomes an emergency if it has been present for more than 3 hours
  2. Examine the person:
    1. Examine for painful, swollen joints
    2. Check the person's temperature
    3. Check the person's pallor:  acute splenic sequestration may present with shock or severe pallor. Because it is most common in young children, parents are taught to palpate the spleen, and they may report an acute increase in splenic size
    4. Palpate for splenomegaly:  on examination there may be significant splenomegaly, but this resolves by the end of the first decade of life because of multiple splenic infarcts

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Management

Screening

lnfants:

  • All newborn infants should be screened for sickle cell disease
  • All infants younger than 1 year of age who have newly arrived in the UK should also be offered screening

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Pregnant women:

  • In high-prevalence areas (more than 1.5 infants born with sickle cell disease per 10,000 births):
    • All pregnant women should be offered screening for sickle cell, thalassaemia, and other haemoglobin variants, using routine blood cell indices and a Family Origin Questionnaire to assist with risk assessment of positive results
    • For women identified as carriers, their baby’s father (irrespective of family origin) is offered testing for sickle cell, other haemoglobin variants, and thalassaemia
  • Low-prevalence areas (1.5 infants or less born with sickle cell disease per 10,000 births):
    • All pregnant women should be offered screening for thalassaemia using routine red blood cell indices
    • Family Origin Questionnaire should be used to screen for the risk of either the woman or the baby’s father being a carrier for sickle cell and other haemoglobin variants. Women in high-risk groups or women whose baby’s father is in a high-risk group are offered laboratory testing for haemoglobin variants
    • All fathers of babies of identified carrier mothers (irrespective of family origin) should be offered testing for sickle cell, other haemoglobin variants, and thalassaemia

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In addition the following people should be screened:

  • All people from high-risk groups who are about to undergo an operation or receive anaesthesia
  • All women who are having assisted conception
  • All women who are being investigated for infertility
  • Ideally, all women in high-risk groups for haemoglobinopathies should be screened before conception. If an abnormality is found, then partners should be offered testing

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Management of sickle cell crisis

  1. Admit all people with clinical features of a sickle cell crisis to hospital unless they are:
    1. A well adult who only has mild or moderate pain and has a temperature of 38°C or less
    2. A well child who only has mild or moderate pain and does not have an increased temperature
  2. Consider admission if the person presents with a fever but is otherwise generally well
    1. Admission is not necessarily required if the source of infection is obvious (such as a viral illness) and can be managed in the community
  3. Have a low threshold for admission:
    1. In a child
    2. If the person has a temperature over 38°C (as there is a risk of rapid deterioration)
    3. If the person has chest symptoms (as acute chest syndrome may develop quickly)
  4. Manage all other people at home:
    1. Ensure that the patient has received a person management plan from secondary care, which should include advice on how to manage their pain, advice on fluid intake and information on trigger factors in order to avoid an acute crisis
    2. If a patient has not received a person management plan prescribe paracetamol and/or ibuprofen and arrange an urgent assessment in hospital if the pain is not controlled by these measures
    3. Advise the person and/or their parents/carer to seek urgent medical advice, or go straight to hospital, if they:
      1. Become unwell or develop a fever with a temperature greater than 38°C (or any increased temperature in a child)
      2. Develop chest symptoms, such as breathlessness
      3. Have severe vomiting or diarrhoea (due to the risk of dehydration)

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Management of chronic complications

Primary care clinicians should:

  1. Admit or refer people immediately if they have new symptoms of cerebrovascular disease, as acute strokes are devastating in both children and adults
  2. Manage chronic pain with care
  3. Treat chest infections early, especially in people with chronic sickle lung
  4. Refer people with eye problems urgently
  5. Refer people for consideration for cholecystectomy if they have symptomatic gallstones
  6. Address concerns about impaired growth or delayed puberty
  7. Manage leg ulcers appropriately
  8. Refer people with suspected pulmonary hypertension, or worsening symptoms
  9. Manage minor episodes of priapism. It is important to enquire about this issue as the person may be too embarrassed to report it
  10. Manage nocturnal enuresis, which is common because of the production of large quantities of dilute urine
  11. Identify renal problems early, and treat hypertension aggressively
  12. Refer people with sleep apnoea
  13. Advise on measures to prevent (or reduce the risk of) complications

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Prevention of complications

  • For children with sickle cell disease, ensure that they receive:
    • Immunizations in accordance with the Childhood Immunization Programme
    • Pneumococcal polysaccharide vaccine (PPV) at 2 years, then every 5 years (that is, at 7, 12, and 17 years of age)
    • Influenza vaccine annually from the age of 6 months
    • Hepatitis B vaccine at 12, 13, and 18 months
    • Meningitis ACWY vaccine, if they are travelling to areas of high risk for meningitis
  • For adults with sickle cell disease, ensure that they receive:
    • The PPV every 5 years
    • One dose of conjugated meningococcal C vaccine, if it has not already been received as part of the primary child immunization schedule
    • One dose of Haemophilus influenzae type B vaccine, if it has not already been received as part of the primary child immunization schedule
    • Hepatitis B vaccine on a 0, 1, and 6-month schedule. Their anti-hepatitis B surface antibody should be tested 1 month after the third dose, and a second full course of the vaccine offered if the response is poor. A booster dose should be offered after 5 years
    • Meningitis ACWY vaccine, if they are travelling to areas of high risk for meningitis

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Antibiotic prophylaxis

NOTE:  Lifelong antibiotic prophylaxis is recommended for all people with sickle cell disease, and it is particularly important that there is full adherence up to 5 years of age

Penicillin prophylaxis should start by 3 months of age

  • The recommended doses are:
    • For children younger than 1 year: 62.5 mg twice a day
    • For children aged 1–5 years: 125 mg twice a day
    • For adults and children older than 5 years of age: 250 mg twice a day
  • The British National Formulary states that if cover is also needed for Haemophilus influenzae in a child or young person, amoxicillin should be given instead. The recommended doses are:
    • For children aged 1 month–5 years: 125 mg twice a day
    • For children aged 5–12 years: 250 mg twice a day
    • For children aged 12–18 years: 500 mg twice daily

If the person is allergic to penicillin, oral erythromycin should be given

  • The recommended doses are:
    • For a child aged 1 month–2 years of age: 125 mg twice a day
    • For children aged 2–8 years: 250 mg twice a day
    • For adults and children older than 8 years of age: 500 mg twice a day

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Folic acid supplementation

NOTE:  Folic acid supplementation is recommended for people with sickle cell disease to prevent deficiency caused by increased folate turnover due to chronic haemolysis and thereby reduce the risk of bone marrow aplasia

Seek specialist advice before prescribing folic acid to determine the optimum dose

  • A dose of 5 mg folic acid once a day is recommended for pregnant women and for women trying to conceive

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Management of sickle cell trait

NOTE:  As sickle cell trait is usually asymptomatic, management consists mainly of providing appropriate advice

  1. Explain to the person with sickle cell traits and/or their family/carers that:
    1. They should very rarely have symptoms. However, they are at risk of a vaso-occlusive episode if they become oxygen deprived. They should therefore:
      1. Avoid high altitudes, such as travelling in an unpressurized aircraft
      2. Inform the anaesthetist that they are sickle cell carriers, if they are going to have an anaesthetic
    2. They have 1 in 2 chance of passing the sickle haemoglobin gene to their child. If the other parent is also a carrier, there is a 1 in 4 chance that their child will have sickle cell disease
    3. It is important to have malaria prophylaxis if they will be visiting an area where malaria is endemic
  2. Refer children and adults with haematuria
  3. Refer children and adults urgently if they present with symptoms suggestive of renal medullary cancer  — haematuria, weight loss, loin pain, fever, and abdominal pain

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Contraception

In general, women with sickle cell disease without complications can use any method of contraception

However, advise the woman to consider using a long-acting reversible contraception (Cu-IUD, LNG-IUS, progestogen-only injectables, progestogen-only implant, or the combined hormonal vaginal ring), as they provide a highly reliable and effective method of contraception (failure rate less than 1 pregnancy per 100 women in a year)

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Family Origin Questionnaire

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Blood tests / Phlebotomy

If your practice does not have a practice nurse who is trained to take bloods, you can refer a patient to the Pathology Department at East Kent Hospitals for a blood test (find details here)

Alternatively, Buckland Hospital (Dover) and the Royal Victoria Hospital (Folkestone) both operate a walk-in service where no appointment is necessary, except for if the patient requires a Glucose Tolerance Test (GTT).  In the event that a GTT is required, please call 01304 222552 (for Buckland) and 01303 854484 (for Royal Victoria) to arrange a suitable appointment

Please ensure that the patient remembers to take with them their blood test form to the walk-in centres

Advice and Guidance is being made available for all specialties, and is being provided by consultant specialists at East Kent Hospitals.  To make a request or to check to if a query has been answered, you will need to log in via the electronic Referral System (eRS)

Click here for the "how to access" e-Referral Advice and Guidance Manual for instructions on how to make a request and check responses

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