Table II.

Summary of systematic reviews and meta-analyses on red blood cell transfusion thresholds.

First author, year	N. of RCT/n. of patients	Target population	Results (restrictive vs liberal transfusion strategy)	Ref.
Salpeter, 2014	3/2,3641	Critically ill patients	Statistically significant reduction in cardiac events (RR: 0.44; 95% CI: 0.22–0.89), re-bleeding (RR: 0.64, 95% CI: 0.45–0.90), bacterial infections (RR: 0.86; 95% CI: 0.73–1.00) and total mortality (RR: 0.80; 95% CI: 0.65–0.98).	24
Curley, 2014	6/1,262	Patients undergoing cardiovascular surgery	Decrease of the number of units of RBC transfused (mean difference: −0.71 units; 95% CI: 0.31–1.09). No significant differences in terms of adverse event rates (mortality, myocardial infarction, stroke, acute renal failure, infections, duration of stay).	25
Brunskill, 2015	6/2,272	Patients undergoing hip fracture surgery	No differences in mortality (RR: 0.92; 95% CI: 0.67–01.26), functional recovery, and post-operative morbidity.	26
Holst, 2015	31/9,813	Surgical and medical patients	Decrease of the number of RBC units transfused (mean difference: −1.43 units; 95% CI: −2.01–0.86). No significant differences in terms of overall morbidity and mortality risks.	28
Fominskiy, 2015	27/11,021	Perioperative and critically ill adult patients	Liberal transfusion strategy compared with restrictive strategy improved survival in peri-operative patients (OR: 0.81, 95% CI: 0.66–1; p=0.005) but not in critically ill patients (OR: 1.10, 95% CI: 0.99–1.23; p=0.07).	30
Ripolles Melchor, 2016	6/2,156	Critically ill patients/patients with ACS	No significant differences in terms of mortality (RR: 0.86, 95% CI: 0.70–1.05; p=0.14).	27
Carson, 2016	31/12,587	Hospitalised adult patients	No significant differences in terms of mortality at 30 days (RR: 0.97; 95% CI: 0.81–1.16), cardiac events (RR: 1.04; 95% CI: 0.79–1.39), cerebrovascular accidents (RR: 0.78; 95% CI: 0.53–1.14) or infections (RR: 0.92; 95% CI: 0.83–1.01).	29
Estcourt, 2017	3/156 + 1/84 (NRS)	Patients with haematological disorders undergoing myelosuppressive chemotherapy or stem cell transplantation	Evidences from RCT Restrictive strategies may make minor or no differences in: - mortality at 100 days (two trials, 95 participants; RR: 0.25, 95% CI: 0.02–2.69, low-quality evidence); - bleeding (two studies, 149 participants; RR: 0.93, 95% CI: 0.73–1.18, low-quality evidence), or clinically significant bleeding (two studies, 149 participants, RR: 1.03, 95% CI: 0.75 to 1.43, low-quality evidence); - number of patients transfused with RBC (three trials, 155 participants; RR: 0.97, 95% CI: 0.90–1.05, low-quality evidence); - duration of hospital stay: restrictive median 35.5 days (IQR: 31.2–43.8) vs liberal median 36 days (IQR: 29.2–44), low-quality evidence. Restrictive strategies could: - decrease the quality of life (one trial, 89 participants; fatigue score: restrictive median 4.8 [IQR: 4–5.2] vs liberal median 4.5 [IQR: 3.6–5], very low-quality evidence); - reduce the risk of developing any serious infection (one study, 89 participants; RR: 1.23, 95% CI: 0.74–2.04, very low-quality evidence). A restrictive RBC transfusion policy may reduce the number of RBC transfusions per participant (two trials, 95 participants; mean difference: −3.58, 95% CI: −5.66 to −1.49, low-quality evidence). Evidence from the NRS Restrictive strategies could: - reduce the risk of death within 100 days (restrictive 1 death vs liberal 1 death; very low-quality evidence); - decrease the risk of clinically significant bleeding (restrictive 3 vs liberal 8; very low-quality evidence); - decrease the number of RBC transfusions (adjusted for age, sex and type of acute myeloid leukaemia: geometric mean: 1.25; 95% CI: 1.07–1.47).	32

¹Only RCT using a restrictive transfusion trigger <7 g/dL were included.

RCT: randomised controlled trial; RR: risk ratio; CI: confidence interval; RBC: red blood cells; OR: odds ratio; ACS: acute coronary syndrome; IQR: interquartile range; NRS: non-randomised study.