Sickle cell disease

Overview

General background | Focus of the review | Comments on evidence | Search and appraisal summary | Substantive changes at this update | Abstract | Cite as

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General background

Sickle cell disease is an autosomal recessive disorder that results in production of abnormal haemoglobin, and is characterised by chronic haemolytic anaemia, dactylitis, and acute episodic clinical events called 'crises'. Sickle cell disease is most common in sub-Saharan Africa and is associated with lifelong morbidity and reduced life expectancy.

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Focus of the review

Effective treatments are needed to reduce morbidity and mortality. This overview looks at the effects of pharmaceutical interventions (antibiotic prophylaxis, hydroxyurea, malaria chemoprophylaxis, and pneumococcal vaccines) to prevent sickle cell crises, including malaria-induced crises and other acute complications. For antibiotic prophylaxis, children aged under 5 years and those 5 years or older were considered separately, as it is thought that the ability to produce an immunological response to encapsulated organisms such as Streptococcus pneumoniae may differ in these groups.

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Comments on evidence

Sickle cell disease is most common in sub-Saharan Africa; however, of the nine RCTs identified in this overview, only two were conducted in this region (in Nigeria and Senegal), with four of the remaining trials conducted in the US and one each in Belgium, India, and Jamaica. Most trials solely included children.

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Search and appraisal summary

The update literature search for this overview was carried out from the date of the last search, March 2010, to January 2015. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 369 studies. After deduplication and removal of conference abstracts, 136 records were screened for inclusion. Appraisal of titles and abstracts led to the exclusion of 99 studies and the further review of 37 full publications. Of the 37 full articles evaluated, three already included systematic reviews were updated, two systematic reviews, two RCTs, and one subsequent RCT were added at this update.

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Additional information

Malaria is endemic in sub-Saharan Africa, where sickle cell disease is also highly prevalent. Plasmodium falciparum malaria is believed to precipitate sickle cell crisis and to increase the risk of death in children with sickle cell anaemia. Consistent use of long-lasting insecticidal nets (LLINs) is a proven cost-effective intervention that is widely promoted to reduce the incidence of malaria and malaria-related deaths. It should be expected that people affected by sickle cell disease who sleep under LLINs consistently will also benefit.

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Substantive changes at this update

Antibiotic prophylaxis in children aged under 5 years One already reported systematic review updated.[17] Categorisation unchanged (beneficial).

Antibiotic prophylaxis in children aged 5 years or older One already included systematic review updated.[17] Categorisation unchanged (unknown effectiveness).

Hydroxyurea Two systematic reviews added[28][29] and two further RCT reports added.[30][31] Categorisation unchanged (likely to be beneficial).

Malaria chemoprohylaxis One already reported systematic review updated[36] and one subsequent RCT added.[37] Categorisation unchanged (likely to be beneficial).

Pneumococcal vaccines One already included systematic review updated.[39] Categorisation unchanged (unknown effectiveness).

Abstract

INTRODUCTION: 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 one 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 overview, aiming to answer the following clinical question: What are the effects of pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2015 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 369 studies. After deduplication and removal of conference abstracts, 136 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 99 studies and the further review of 37 full publications. Of the 37 full articles evaluated, three already included systematic reviews were updated, two systematic reviews, two RCTs, and one subsequent RCT were added at this update. We performed a GRADE evaluation for 12 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for five interventions based on information about the effectiveness and safety of antibiotic prophylaxis in children aged under 5 years, antibiotic prophylaxis in children aged 5 years or older, hydroxyurea, malaria chemoprophylaxis, and pneumococcal vaccines.

Cite as

Meremikwu MM, Okomo U. Sickle cell disease. Systematic review 2402. BMJ Clinical Evidence. . 2016 January. Accessed [date].

Latest citations

Prophylactic versus selective blood transfusion for sickle cell disease in pregnancy. ( 11 January 2017 )

Interventions for patients and caregivers to improve knowledge of sickle cell disease and recognition of its related complications. ( 10 January 2017 )