Key messages
In children and adolescents, for whom abnormally shaped red blood cells caused by sickle-cell disease (SCD) put them at high risk of stroke, long-term transfusions of normal red blood cells (RBCs) probably decrease the risk of stroke compared to standard care, and may also decrease the risk of painful crisis (when sickle-shaped RBCs block small blood vessels) and acute chest syndrome (a potentially fatal blockage of vessels in the lungs).
RBC transfusions may increase the risk of developing an antibody against transfused RBCs and of developing iron overload (too much iron in the blood).
Most evidence available applies to children with a specific type of SCD (HbSS disease); more evidence is needed for adults and children with other types of SCD.
What is sickle cell disease?Sickle cell disease (SCD) is a serious, inherited blood disorder where the red blood cells (RBCs), which carry oxygen around the body, become abnormally shaped ('sickled'). Normal RBCs are flexible and disc-shaped, but sickled red blood cells are rigid and crescent shaped. Sickled RBCs are stickier and less flexible than normal RBCs, which can lead to blockage of blood vessels, tissue damage, organ damage, and episodes of severe pain. Sickled RBCs are fragile and break apart easily; this leads to a condition called anaemia (too few RBCs in the blood).How is sickle cell disease treated?Transfusions of healthy RBCs are used to treat SCD in different ways:
a 'top-up' of normal, non-sickle-cell blood can be given for anaemia;
an 'exchange transfusion' where some of a person's sickle-cell blood is removed and replaced with normal blood. This reduces the proportion of sickled RBCs and can relieve emergencies, such as stroke or acute chest syndrome;
long-term, regular – usually monthly – transfusions for prevention of stroke, especially when medications, such as hydroxycarbamide (to decrease the likelihood of painful crises), don't work.
What did we want to find out?We wanted to find out when RBC transfusions should be used in SCD to prevent:
death due to any cause;
SCD complications, such as stroke, acute chest syndrome, painful crises.
We also wanted to know about any unwanted effects from RBC transfusions, such as:
transfusion reactions (allergic reactions, breakdown of RBCs, fever);
development of antibodies against the transfused RBCs (when a person's body fights against the transfused blood);
build up of too much iron in organs such as the liver, heart and pancreas (iron overload).
We looked at several ways that RBC transfusions could be used:
RBC transfusions versus no RBC transfusions;
RBC transfusions plus normal care (painkillers, fluids via a drip, oxygen) versus normal care only;
RBC transfusions versus medicines (e.g. hydroxycarbamide) to reduce the complications of SCD;
RBC transfusions to reverse anaemia versus exchange transfusions to lower the proportion of sickle cells in blood.
What did we do?We searched for Cochrane reviews that analysed evidence from studies that had investigated how well RBC transfusions prevented or treated SCD complications. This overview summarises the results of these reviews, and is an update of a previously published Cochrane overview.What did we find?We found 17 relevant reviews, however, only 5 reviews had found studies that provided evidence about the effects of RBC transfusion and had results that we could use (9 studies, 1502 participants).All 9 studies were conducted in high-income countries (USA, Canada, France, UK), so their findings may not be very helpful for low- and middle-income countries, where transfusions are not readily available and transfusion-associated risks differ. Most of the evidence related to children with the HbSS version of SCD. There was very little evidence about adults with SCD-related complications, and important information, such as quality of life, were often not measured or reported.The 5 reviews showed there may be little or no difference in the risk of death with any of the treatments (death was very rare). We found that in children and adolescents with a high risk of stroke (identified by a specialised ultrasound test), or who have had a 'silent stroke' (a stroke with no outward symptoms), long-term RBC transfusions compared to standard care:
probably decrease the risk of stroke;
may decrease the risk of painful crisis and acute chest syndrome; and
may decrease the risk of silent stroke in children with abnormal ultrasound results.
However, RBC transfusions may be associated with an increased risk of developing antibodies against transfused RBCs and of developing iron overload.What are the limitations of the evidence?There is very little evidence about RBC transfusion for complications of SCD. Most of the evidence applies only to children with a specific type of SCD (HbSS disease). People with SCD are living longer, so we need better evidence about when and how to use RBC transfusions to treat adults with SCD, and how to treat children with other types of SCD. How up to date is the evidence?The evidence is up to date to June 2026.