Blood transfusion for preventing stroke in people with sickle cell disease

Background

In sickle cell disease (SCD), a common inherited haemoglobin disorder, abnormal haemoglobin distorts red blood cells, causing anaemia, vaso-occlusion and dysfunction in most body organs. Stroke affects around 10% of children with sickle cell anaemia and recurrence is likely. Chronic blood transfusion dilutes the sickled red blood cells, reducing the risk of vaso-occlusion and stroke. However, side effects can be severe.

Objectives

To assess risks and benefits of chronic blood transfusion regimens in people with SCD to prevent first stroke or recurrences.

Search strategy

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and conference proceedings.

Last search of the Group's Trials Register: 22 May 2009.

Selection criteria

Randomised and quasi-randomised controlled trials comparing blood transfusion as prophylaxis for stroke in people with SCD to alternative or no treatment.

Data collection and analysis

Both authors independently assessed trial quality and extracted data.

Main results

Searches identified two eligible trials. One compared a chronic transfusion regimen for maintaining sickle haemoglobin lower than 30% with standard care in 130 children with SCD judged (through transcranial doppler ultrasonography) as high-risk for first stroke. During the trial, 11 children in the standard care group suffered a stroke compared to one in the transfusion group. This 92% relative risk reduction meant the trial was terminated early. Thirty months treatment was planned, but median follow up was 21.1 months. The transfusion group had a high complications rate: iron overload; alloimmunisation; and transfusion reactions. The second trial investigated risk of stroke when transfusion was stopped after at least 30 months. The trial closed early due to a significant difference in risk of stroke between participants who stopped transfusion and those who continued (for whom it was deemed unsafe to recommend discontinuation), as measured by abnormal velocities on Doppler examinations, OR 0.02 (95% CI 0.00 to 0.43). No trials were identified investigating transfusion for preventing recurrence of stroke.

Authors' conclusions

These trials demonstrated a significantly reduced risk of stroke in participants receiving regular blood transfusions. Data from a follow-up trial indicate individuals may revert to former risk status if transfusion is discontinued. Degree of risk must be balanced against the burden of chronic transfusions. Further research is required examining the use of transfusion in preventing secondary stroke, and further defining risk factors for stroke, to avoid unnecessarily starting children on blood transfusions.