Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to a third of adults are carriers of the defective sickle cell gene, and 1% to 2% of babies are born with the disease.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: what are the effects of pharmaceutical and non-pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? What are the effects of pharmaceutical and non-pharmaceutical interventions to treat pain in people with sickle cell crisis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 38 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, antibiotic prophylaxis in children <5 years of age, antibiotic prophylaxis in children >5 years of age, aspirin, avoidance of cold environment, blood transfusion, codeine, corticosteroid (with narcotic analgesics), diflunisal, hydration, hydroxyurea, ibuprofen, ketorolac, limiting physical exercise, malaria chemoprophylaxis, morphine (controlled-release oral after initial intravenous bolus, repeated intravenous doses), oxygen, paracetamol, patient-controlled analgesia, pneumococcal vaccines, and rehydration.
In sub-Saharan Africa, up to a third of adults are carriers of the defective sickle cell gene, and 1% to 2% of babies are born with the disease.
Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion.
We don’t know whether avoidance of cold environments, physical exercise, or rehydration can prevent crises or complications in people with sickle cell disease.
Blood transfusion (prophylactic) reduces stroke in children at increased risk of stroke, but increases the risks of iron overload, allo-immunisation, hypertensive or circulatory overload, febrile non-haemolytic reactions, allergic reactions, and haemolytic events.
Penicillin prophylaxis in children <5 years of age reduces invasive pneumococcal infections regardless of pneumococcal vaccination status. We don’t know whether penicillin prophylaxis is beneficial in older children.
Malaria chemoprophylaxis is considered useful in preventing malaria-induced crises, but we found few studies evaluating its benefit.Polyvalent polysaccharide pneumococcal vaccine does not reduce the incidence of pneumococcal infections in people with sickle cell disease. Pneumococcal conjugate vaccines have been reported to have protective efficacy in children <2 years of age, but this protective effect has not been shown in infants with sickle cell disease.
Hydroxyurea may reduce some complications of sickle cell disease, such as painful crises compared with placebo, but long-term effects and safety are unknown.
Morphine is widely used to treat severe pain, but we found no RCT evidence comparing it with placebo in people with sickle cell crises. Controlled-release oral morphine and patient-controlled analgesia may be as effective as repeated intravenous doses of morphine. Oral morphine increases the risk of acute chest syndrome compared with intravenous administration.
High-dose corticosteroids may reduce the need for analgesia when added to intravenous morphine in people with a sickle cell crisis, but may increase the risks of adverse effects (such as infections, hypertension, and metabolic problems).
It is still unclear whether acupuncture, blood transfusion, hydration, oxygen, aspirin, codeine, diflunisal, ibuprofen, ketorolac, or paracetamol reduce pain during sickle cell crisis.