Table 1

Characteristics of included randomized clinical trials

Author surname; year published; country conductedMethodsEligibility criteriaInterventions (fresh vs standard or older stored blood); reported definition; age of blood in treatment arms (fresher vs older or stored)
Steiner; 2015; USA26  Multicenter, patients undergoing cardiac surgery, at 33 US hospitals. ≥12 y of age and eligible if weighed ≥40 kg and scheduled for complex cardiac surgery, those ≥18 y of age to have a score of 3 or higher on the TRUST scale (corresponds to a high likelihood of receiving RBC transfusions during surgery or within 96 h postoperatively). Randomized to units stored for ≤10 d or to units stored for ≥21 d for all transfusions from randomization through postoperative day 28, discharge or death (the first to occur), leukocyte reduced.
Definition: shorter- vs longer-term storage
Mean fresh: 7.8 ± 4.8 d SD
Mean older: 28.3 ± 6.7 d SD 
Hebert; 2005; Canada42  Multicenter, pilot study of patients admitted to ICU at 1 of 4 Canadian hospitals. Adults >16 y who required at least 1 unit of RBCs, accepted to participate in the study, and were either undergoing elective or urgent cardiac surgical procedures or admitted to an ICU. Randomized to either RBCs stored <8 d or standard issue RBCs based on standard blood bank procedure, leukocyte-reduced.
Definition: <8 d was deemed fresh blood and standard issue was considered older blood
Median fresh: 4 d
Median older: 19 d
Median difference: 15 d IQR 12-16 d 
Lacroix; 2015; Canada and Europe27  Multicenter, critically ill ICU patients in 64 hospitals. ≥18 y, and eligible if a first RBC transfusion was prescribed within 7 d after admission to the ICU and if they were expected to require invasive or noninvasive mechanical ventilation for at least 48 h. Randomized to RBC units stored for ≤8 d or to RBC units that were standard issue, units were leukocyte-reduced.
Definition: <8 d (fresh) vs usual transfusion practice (oldest available compatible blood)
Mean fresh: 6.1 ± 4.9 d SD
Mean older: 22.0 ± 8.4 d SD 
Aubron; 2012; Australia44  Multicenter, feasibility pilot, ICU admitted, critically ill patients. ≥18 y, and prescribed at least 1 unit of RBCs. Randomized to fresher blood (freshest available) vs older stored blood (oldest available), units were leukocyte-reduced.
Definition: fresh blood units found at the back of the transfusion service storage refrigerator and older/stored (nonexpired) units located at the front of the refrigerator (compatible, nonexpired [RBC] units with the longest storage duration at the time of transfusion request)
Mean fresh: 12.1 ± 3.8 d SD
Mean older: 23.0 ± 8.4 d SD 
Bennett-Guerrero; 2009; USA37  Single-center, reporting on the first phase of a 2-phase pilot, patients undergoing cardiac surgery. ≥18 y, a preoperative Parsonnet risk score >15 (indicative of greater morbidity and mortality risk), and scheduled for nonemergent coronary artery bypass graft and/or cardiac valve repair or replacement surgery using CPB. Randomized to no RBCs >21 days old vs standard of care for the phase 1 study, leukocyte-reduced.
Definition: blood age was defined as fresher or no RBCs >21 days old vs standard of care
Mean fresh: no RBCs > 21 d
Mean older: standard of care 
Dhabangi; 2013; Uganda45  Single-center pilot, open-label feasibility clinical trial, in children with severe malarial anemia. Aged six to 59 months enrolled if they had a positive blood smear for malaria, severe anemia (Hb ≤5 g/dL), lactic acidosis (blood lactate ≥5 mmol/L), and written informed consent from the parent or guardian. Randomized to RBCs that were of short storage age or long storage age.
Definition: short = 1-10 d vs long storage = 21-35 d
Mean fresh: 7.8 ± 1.8 d SD
Mean older: 27.2 ± 3.9 d SD 
Fergusson; 2012; Canada43  Multicenter, 6 Canadian tertiary NICUs/hospitals, in premature infants. Admitted to each of the participating neonatal ICUs with a birth weight of <1250 g and requiring one or more RBC transfusion for the treatment of anemia. Randomized to RBCs stored ≤7 d vs standard-issue/practice.
Definition: RBCs stored for ≤7 d (fresh blood) vs current standard-issue RBCs with storage time ranging from 2-42 d as per site
Mean fresh: 5.1 ± 2.0 d SD
Mean older: 14.6 ± 8.3 d SD 
Fernandes da Cunha; 2005; Brazil46  Single-center, university hospital setting, very-low-birth-weight children. Gestational age <37 wk, birth weight <1500 g, received at least one transfusion in hospital, and parents signed consent. Randomized to group 2 or fresh arm (up to 3 d age of blood) and to group 1 or older arm (blood stored for up to 28 d), leukocyte-reduced.
Definition: fresher blood was blood stored up to 3 d and older blood was stored up to 28 d
Mean fresh: 1.6 ± 0.6 d SD
Mean older: 9.0 ± 8.9 d SD 
Heddle; 2012; Canada47  Single-center pilot trial, consecutive patients admitted to an academic acute care hospital. Adult patients (≥17 y) hospitalized and requiring a blood transfusion. Randomized to either the freshest available or standard issue, leukocyte-reduced.
Definition: no clear numerical demarcation, freshest blood available vs standard issue blood
Mean fresh: 12 ± 6.8 d SD
Mean older: 26.6 ± 7.8 d SD 
Kor; 2012; USA48  Single-center, medical or surgical patients admitted to an ICU at Mayo clinic. Adults >18 y admitted for cardiac or neurologic surgery, endotracheally intubated and mechanically ventilated, and having arterial access in situ and Hb <9.5 g/dL. Randomized to either fresh arm (blood ≤5 d of storage) or standard issue, leukocytel-reduced.
Definition: Fresh arm is blood ≤5 d of storage and standard issue had a historic median storage duration of 21 d (range, 7-42)
Median fresh: 4 d, IQR 3-5 d
Median older: 26.5 d, IQR 21-36 d 
Schulman; 2002; USA49  Single-center, level I trauma hospital, published as a letter and not full manuscript, little details were provided. Patients admitted to trauma center and having blood type A, for support during acute illness/severe injuries. Randomized to young blood or old blood, leukocyte-reduced.
Definition: young blood was blood aged <11 d and old blood was blood aged >20 d
Not reported 
Strauss; 1996; USA50  Single-center study comparing the feasibility and safety of 2 techniques for providing small-volume RBC transfusions to very-low-birth-weight infants. Infants weighing 0.6-1.3 kg were potential trial subjects upon admission to the NICU, transfusion support during acute illness. Randomized to fresh blood or standard-practice storage, leukocyte-reduced.
Definition: fresh blood was ≤7 d and old blood was standard practice (<42 d)
Not reported 
Author surname; year published; country conductedMethodsEligibility criteriaInterventions (fresh vs standard or older stored blood); reported definition; age of blood in treatment arms (fresher vs older or stored)
Steiner; 2015; USA26  Multicenter, patients undergoing cardiac surgery, at 33 US hospitals. ≥12 y of age and eligible if weighed ≥40 kg and scheduled for complex cardiac surgery, those ≥18 y of age to have a score of 3 or higher on the TRUST scale (corresponds to a high likelihood of receiving RBC transfusions during surgery or within 96 h postoperatively). Randomized to units stored for ≤10 d or to units stored for ≥21 d for all transfusions from randomization through postoperative day 28, discharge or death (the first to occur), leukocyte reduced.
Definition: shorter- vs longer-term storage
Mean fresh: 7.8 ± 4.8 d SD
Mean older: 28.3 ± 6.7 d SD 
Hebert; 2005; Canada42  Multicenter, pilot study of patients admitted to ICU at 1 of 4 Canadian hospitals. Adults >16 y who required at least 1 unit of RBCs, accepted to participate in the study, and were either undergoing elective or urgent cardiac surgical procedures or admitted to an ICU. Randomized to either RBCs stored <8 d or standard issue RBCs based on standard blood bank procedure, leukocyte-reduced.
Definition: <8 d was deemed fresh blood and standard issue was considered older blood
Median fresh: 4 d
Median older: 19 d
Median difference: 15 d IQR 12-16 d 
Lacroix; 2015; Canada and Europe27  Multicenter, critically ill ICU patients in 64 hospitals. ≥18 y, and eligible if a first RBC transfusion was prescribed within 7 d after admission to the ICU and if they were expected to require invasive or noninvasive mechanical ventilation for at least 48 h. Randomized to RBC units stored for ≤8 d or to RBC units that were standard issue, units were leukocyte-reduced.
Definition: <8 d (fresh) vs usual transfusion practice (oldest available compatible blood)
Mean fresh: 6.1 ± 4.9 d SD
Mean older: 22.0 ± 8.4 d SD 
Aubron; 2012; Australia44  Multicenter, feasibility pilot, ICU admitted, critically ill patients. ≥18 y, and prescribed at least 1 unit of RBCs. Randomized to fresher blood (freshest available) vs older stored blood (oldest available), units were leukocyte-reduced.
Definition: fresh blood units found at the back of the transfusion service storage refrigerator and older/stored (nonexpired) units located at the front of the refrigerator (compatible, nonexpired [RBC] units with the longest storage duration at the time of transfusion request)
Mean fresh: 12.1 ± 3.8 d SD
Mean older: 23.0 ± 8.4 d SD 
Bennett-Guerrero; 2009; USA37  Single-center, reporting on the first phase of a 2-phase pilot, patients undergoing cardiac surgery. ≥18 y, a preoperative Parsonnet risk score >15 (indicative of greater morbidity and mortality risk), and scheduled for nonemergent coronary artery bypass graft and/or cardiac valve repair or replacement surgery using CPB. Randomized to no RBCs >21 days old vs standard of care for the phase 1 study, leukocyte-reduced.
Definition: blood age was defined as fresher or no RBCs >21 days old vs standard of care
Mean fresh: no RBCs > 21 d
Mean older: standard of care 
Dhabangi; 2013; Uganda45  Single-center pilot, open-label feasibility clinical trial, in children with severe malarial anemia. Aged six to 59 months enrolled if they had a positive blood smear for malaria, severe anemia (Hb ≤5 g/dL), lactic acidosis (blood lactate ≥5 mmol/L), and written informed consent from the parent or guardian. Randomized to RBCs that were of short storage age or long storage age.
Definition: short = 1-10 d vs long storage = 21-35 d
Mean fresh: 7.8 ± 1.8 d SD
Mean older: 27.2 ± 3.9 d SD 
Fergusson; 2012; Canada43  Multicenter, 6 Canadian tertiary NICUs/hospitals, in premature infants. Admitted to each of the participating neonatal ICUs with a birth weight of <1250 g and requiring one or more RBC transfusion for the treatment of anemia. Randomized to RBCs stored ≤7 d vs standard-issue/practice.
Definition: RBCs stored for ≤7 d (fresh blood) vs current standard-issue RBCs with storage time ranging from 2-42 d as per site
Mean fresh: 5.1 ± 2.0 d SD
Mean older: 14.6 ± 8.3 d SD 
Fernandes da Cunha; 2005; Brazil46  Single-center, university hospital setting, very-low-birth-weight children. Gestational age <37 wk, birth weight <1500 g, received at least one transfusion in hospital, and parents signed consent. Randomized to group 2 or fresh arm (up to 3 d age of blood) and to group 1 or older arm (blood stored for up to 28 d), leukocyte-reduced.
Definition: fresher blood was blood stored up to 3 d and older blood was stored up to 28 d
Mean fresh: 1.6 ± 0.6 d SD
Mean older: 9.0 ± 8.9 d SD 
Heddle; 2012; Canada47  Single-center pilot trial, consecutive patients admitted to an academic acute care hospital. Adult patients (≥17 y) hospitalized and requiring a blood transfusion. Randomized to either the freshest available or standard issue, leukocyte-reduced.
Definition: no clear numerical demarcation, freshest blood available vs standard issue blood
Mean fresh: 12 ± 6.8 d SD
Mean older: 26.6 ± 7.8 d SD 
Kor; 2012; USA48  Single-center, medical or surgical patients admitted to an ICU at Mayo clinic. Adults >18 y admitted for cardiac or neurologic surgery, endotracheally intubated and mechanically ventilated, and having arterial access in situ and Hb <9.5 g/dL. Randomized to either fresh arm (blood ≤5 d of storage) or standard issue, leukocytel-reduced.
Definition: Fresh arm is blood ≤5 d of storage and standard issue had a historic median storage duration of 21 d (range, 7-42)
Median fresh: 4 d, IQR 3-5 d
Median older: 26.5 d, IQR 21-36 d 
Schulman; 2002; USA49  Single-center, level I trauma hospital, published as a letter and not full manuscript, little details were provided. Patients admitted to trauma center and having blood type A, for support during acute illness/severe injuries. Randomized to young blood or old blood, leukocyte-reduced.
Definition: young blood was blood aged <11 d and old blood was blood aged >20 d
Not reported 
Strauss; 1996; USA50  Single-center study comparing the feasibility and safety of 2 techniques for providing small-volume RBC transfusions to very-low-birth-weight infants. Infants weighing 0.6-1.3 kg were potential trial subjects upon admission to the NICU, transfusion support during acute illness. Randomized to fresh blood or standard-practice storage, leukocyte-reduced.
Definition: fresh blood was ≤7 d and old blood was standard practice (<42 d)
Not reported 

CPB, cardiopulmonary bypass (machine); Hb, hemoglobin; ICU, intensive care unit; IQR, interquartile range; NICU, neonatal intensive care unit; RBC, red blood cell.

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