Red blood cell transfusion to treat or prevent complications in sickle cell disease: an overview of Cochrane reviews

Background Globally, sickle cell disease (SCD) is one of the commonest severe monogenic disorders, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end‐organ damage, pulmonary complications, and premature death. Red blood cell (RBC) transfusions are used to treat complications of SCD, e.g. acute chest syndrome (ACS) (this often involves a single transfusion episode), or they can be part of a regular long‐term transfusion programme to prevent SCD complications. Objectives To summarize the evidence in Cochrane Reviews of the effectiveness and safety of RBC transfusions versus no transfusion, or restrictive (to increase the total haemoglobin) versus liberal (to decrease the haemoglobin S level below a specified percentage) transfusion, for treating or preventing complications experienced by people with SCD. Methods We included Cochrane Reviews of randomised or quasi‐randomised controlled trials published in the Cochrane Database of Systematic Reviews, that addressed various SCD complications and had RBC transfusion as an intervention or comparator. We assessed the methodological quality of included reviews according to the AMSTAR quality assessment. Main results We included 15 Cochrane Reviews, 10 of which had no included studies with an RBC transfusion intervention (five reported RCTs with other interventions; and five contained no studies). Five of the 15 reviews included participants randomised to RBC transfusion, but in one of these reviews only 10 participants were randomised with no usable data. Four reviews (nine trials with 1502 participants) reported data comparing short‐ or long‐term RBC transfusions versus standard care, disease‐modifying agents, a restrictive versus a liberal transfusion strategy and long‐term RBC transfusions versus transfusions to treat complications. All reviews were of high quality according to AMSTAR quality assessment, however, the quality of the included trials was highly variable across outcomes. Trials were downgraded according to GRADE methodology for risk of bias, indirectness (most trials were conducted in children with HbSS), and imprecision (outcomes had wide confidence intervals). In all four reviews and all comparisons there was little or no difference in the risk of death (very low‐quality evidence). There were either no deaths or death was a rare event. Short‐term RBC transfusion versus standard care (one review: two trials, 434 participants, GRADE ver