Sickle cell anaemia

The diagnosis, features and management of sickle cell anaemia, including identifying and dealing with sickle cell anaemia crises.

Blood film of a patient with sickle cell disease, with sickle cells, target cells and signs of hyposplenism (Photograph: Dr Patel)
Blood film of a patient with sickle cell disease, with sickle cells, target cells and signs of hyposplenism (Photograph: Dr Patel)

Sickle cell anaemia was the first disease in which the molecular pathogenesis was identified and is now the most common genetic disease in England.

Inadequate expertise and management, particularly in areas of low prevalence, have contributed to significant morbidity and mortality.1


Sickle cell anaemia occurs due to mutations in both copies of the beta-globin genes, which result in a single amino acid change in the beta chain of haemoglobin. Sickle haemoglobin (HbS) is produced in the absence of normal adult haemoglobin (HbA). In HbS, the glutamic acid residue at position six is replaced by valine. This reduces the solubility of deoxyhaemoglobin and results in a conformational change within red cells, producing the characteristic sickle-shaped red cells seen on a blood film.

These cells are significantly less malleable and accompanying changes in the red cell membrane increase their adherence to the vascular endothelium.

The general term sickle cell disease includes other conditions that lead to formation of sickle red cells, such as co-inheritance of HbS and other beta-chain variants, such as haemoglobin C, or beta-thalassaemia trait.


An estimated 12,500 patients in the UK have sickle cell disease.1 It is most prevalent in people of African, Caribbean, eastern Mediterranean, Middle Eastern and Asian origin.


The NHS sickle cell and thalassaemia screening programme is for all pregnant women and newborn babies and uses the Guthrie test. Children with sickle cell anaemia usually have a chronic normocytic anaemia of 6-9g/dl with a reticulocytosis, observed from 10 weeks of age. Microcytosis might suggest co-inheritence of thalassaemia and or iron deficiency. Sickle cells are seen on a blood film, sometimes accompanied by signs of hyposplenism.

The sickle solubility test is a rapid screening process that will diagnose the presence of significant sickle cells. A positive result must be confirmed by haemoglobin electrophoresis, or high-performance liquid chromatography, both of which take longer but more precisely identify the haemoglobinopathy.

Clinical features

The overall mean painful crisis rate of sickle cell anaemia is 0.8 episodes per person-year.2 Variation is marked, with up to 30 per cent of patients in one large study not suffering any painful crises, while 5.2 per cent of patients with 3-10 crises per year comprised a third of all pain episodes.

Types of crises and major pain syndromes in patients with sickle cell anaemia2

Types of sickle crises

Acute pain syndrome

Chronic pain syndrome


Acute chest syndrome






Hand-foot syndrome

Aseptic necrosis

Aplastic crisis (parvovirus B19)

Painful episodes

Leg ulcers

Sequestration (mainly children; splenic or hepatic)


Vertebral body collapse

Leg ulceration

Right upper quadrant syndrome
Splenic sequestration


Higher pain scores are associated with a raised haematocrit, lower fetal haemoglobin, higher baseline lactate dehydrogenase, and premature death. Some patients experience predominantly haemolytic symptoms while others experience a more thrombotic phenotype. However, significant inflammatory vasculopathy and local nitric oxide depletion with free haemoglobin are now recognised causes of symptomatic complications.

In addition to these crises exacerbating steady state anaemia, autoimmunity, sepsis, medications and glucose-6-phosphate dehydrogenase deficiency must also be considered.


Factors known to precipitate a crisis should be avoided. Precipitants include infection, dehydration, hypoxia and cold temperature. Rapid, adequate analgesics with rehydration, warmth and additional oxygen are crucial. Respiratory infection should be excluded by chest radiography and appropriate cultures, with a low threshold for commencing antibiotics.

Red cell transfusion can support aplastic or sequestration crises but may increase viscosity in the context of painful crises.

Frequent crises and complications may be prevented by enrolment onto a regular transfusion programme.

This suppresses HbS formation and reduces the frequency of crises.

An exchange blood transfusion aims to reduce HbS to less than 20 per cent and can be used for acute life-threatening or severe complications, such as a chest crisis or stroke. Transfusions may be complicated by reactions (acute or delayed), alloimmune antibody formation, hyperhaemolysis, iron overload and eventually loss of vascular access.

Hydroxycarbamide reduces the frequency and severity of crises, perhaps by increasing fetal haemoglobin levels. Patients taking their medication often develop macrocytosis. Children (and some adults) with severe disease may receive an allogeneic haematopoietic stem cell transplant, and can expect a 95 per cent overall survival rate.

A GP's crucial holistic role cannot be overemphasised when caring for patients with sickle cell anaemia. This includes:

  1. Early treatment of infections to prevent sepsis and or acute chest syndrome.
  2. Antibiotic prophylaxis of hyposplenism (penicillin or erythromycin).
  3. Vaccination - influenza A and the UK immunisation schedule, including Haemophilus influenzae type B, Neisseria meningitidis group C and Streptococcus pneumoniae.
  4. Folic acid prophylaxis to prevent deficiency from haemolysis.
  5. Monitoring for aplastic crisis (parvovirus B19 infection).
  6. Antenatal/neonatal screening and referral of pregnant women.
  7. Psychological support and counselling.
  8. Encourage treatment compliance.
  9. Patient education and self-management and mildly painful episodes.
  10. Treatment and prophylaxis of vascular risk factors.
  11. Monitor for renal disease, including proteinuria.

Prognosis and outcome

The median life expectancy for sickle cell disease is around 50 years.

The National Confidential Enquiry into Patient Outcome and Death report concluded that the cause of deaths of acutely ill sickle cell disease patients frequently remains unclear.3

Around 20 per cent of deaths are associated with a painful crisis, 15 per cent with a chest syndrome, 10 per cent with renal failure or infection and 5 per cent peri-operatively. Sudden death remains a significant problem.

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This is an updated version of an article that was first published in October 2010.


  1. All-Party Parliamentary Group on Sickle Cell and Thalassaemia. Sickle Cell Disease and Thalassaemia: A Health Check. DoH, London. 2009.
  2. The Management of Sickle Cell Disease. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda. 4th edition, revised 2002.
  3. A sickle crisis? A report of the National Confidential Enquiry into Patient Outcome and Death (2008). DoH,

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