- Email: [email protected]
Finally, what we have been waiting for: evidence that transfusion of RBCs at the extreme of the storage spectrum is safe
Comment
In 2008, investigators at the Cleveland Clinic published a retrospective study comparing outcomes after cardiac surgery for patients transfused with freshly collected red blood cells (RBCs; stored <2 weeks) versus old RBCs (stored >2 weeks).1 Transfusion with old RBCs was associated with more complications post-surgery and increased mortality. Since then, one of the major controversies in transfusion medicine has been whether a lesion develops during RBC storage, which could result in inferior recipient outcomes. This question has been addressed in more than ten reported trials, none of which have yielded data that show a significant advantage of fresh RBCs compared with old RBCs. A variety of patient populations have been studied (including intubated adults in the intensive care setting, general hospital patients, and neonates).2–6 However, whether the oldest RBCs, in their final week of storage, could be associated with increased risk of recipient morbidity or mortality, or both, compared to RBCs that were transfused within 1 week of collection has never been investigated. Because preliminary evidence suggests RBCs at the end of the current allowed storage period might cause harm,7–8 some stakeholders in transfusion medicine have even wondered whether it would be ethical to conduct a trial in which some patients are randomly assigned to transfusion with RBCs that have been stored for more than 35 days. In The Lancet Hematology, Cook and colleagues9 present the results of a secondary analysis of the INFORM trial data to investigate whether transfusion with RBCs after 35–42 days of storage was associated with worse outcomes than transfusion with RBCs that had been stored for less than a week. The INFORM trial was a ran domised controlled, multicentre, multinational trial of the effect of storage duration on patient in-hospital mortality.5 Importantly, the INFORM trial included more than 24 000 patients and was powered for mortality; this is far more patients than were enrolled in any other large trials, which cumulatively enrolled about 5000 patients.2,3 Of 24 726 patients included in the secondary analysis, 4480 (18%) patients were exposed to RBCs with longest www.thelancet.com/haematology Vol 4 November 2017
storage, 1392 (6%) patients were exposed exclusively to RBCs with shortest storage, and 18 854 (76%) patients were exposed to RBCs stored 8–35 days. The authors found equivalent risk for in-hospital death in patients who were transfused with RBCs stored for durations at either end of the storage range. In a multivariable model including patients of all blood types and adjusting for patient demographics, diagnosis, and blood product use, transfusion of RBCs stored for more than 35 days was not associated with increased mortality compared with transfusion of RBCs stored 7 days or less (hazard ratio 0·91, 95% CI 0·72–1·14; p=0·40). One limitation of this study is that individuals who received old RBCs did not exclusively receive RBCs that had been stored for longer than 35 days. However, the high number of patients involved in the INFORM study should be sufficient to quell worry that the study was insufficiently powered to detect a worrisome signal. The overall study finding is of substantial interest to the practice of transfusion medicine, as none of the previous clinical trials assessing the age of blood were able to compare outcomes for patients receiving RBCs at the extremes of storage life. In addition to their implications on patient care, the trial data will probably have regulatory importance. The transfusion medicine community has been concerned about the possibility of lesions developing in blood towards the end of allowed storage period. Some transfusions services in both the USA and Europe are already restricting the transfusion of the oldest RBCs.10 Additionally, transfusion specialists speculated that regulatory bodies would re-evaluate the licensed dating period of RBCs. The transfusion community has been anxiously asking questions about best practice, and these data presented by Cook and colleagues seem to have provided a definitive answer. Reassuringly, the findings are consistent with AABB’s recent transfusion guidelines,2 which state that “patients should receive RBC units selected at any point within their licensed dating period rather than limiting patients to transfusion of only fresh RBC units”.
Garo/Phanie/Science Photo Library
Finally, what we have been waiting for: evidence that transfusion of RBCs at the extreme of the storage spectrum is safe
Published Online October 9, 2017 http://dx.doi.org/10.1016/ S2352-3026(17)30179-5 See Articles page e544
e504
Comment
After so many studies, it seems that the transfusion medicine community can finally be reassured that patient outcomes are not meaningfully altered by transfusing RBCs that are approaching their 42-day outdate. Eric A Gehrie, *Aaron A R Tobian Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA [email protected] We declare no competing interests. 1 2 3
e505
Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med 2008; 358: 1229–39. Carson JL, Guyatt G, Heddle NM, et al. Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA 2016; 316: 2025–35. Alexander PE, Barty R, Fei Y, et al. Transfusion of fresher versus older red blood cells in hospitalized patients: a systematic review and meta-analysis. Blood 2016; 127: 400–10.
4
Kor DJ, Kashyap R, Weiskopf RB, et al. Fresh red blood cell transfusion and short-term pulmonary, immunologic, and coagulation status. Am J Respir Crit Care Med 2012; 185: 842–50. 5 Heddle NM, Cook RJ, Arnold DM, et al. Effect of short-term vs long-term blood storage on mortality after transfusion. N Engl J Med 2016; 375: 1937–45. 6 Fergusson DA, Bebert P, Hogan DL, et al. Effect of fresh red blood cell transfusions on clinica outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial. JAMA 2012; 308: 1443–51. 7 Rapido F, Brittenham GM, Bandyopadhyay S, et al. Prolonged red cell storage before transfusion increases extravascular hemolysis. J Clin Invest 2017; 127: 375–82. 8 Goel R, Johnson DJ, Scott AV, et al. Red blood cells stored 35 days or more are associated with adverse outcomes in high-risk patients. Transfusion 2016; 56: 1690–98. 9 Cook RJ, Heddle NM, Lee K-A, et al. Red blood cell storage duration and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial. Lancet Haematol 2017; published online Oct 9. http://dx.doi. org/10.1016/S2352-3026(17)30169-2. 10 Klein HG, Cortes-Puch I, Natanson C. More on the age of transfused red cells. N Engl J Med 2015; 373: 283.
www.thelancet.com/haematology Vol 4 November 2017
In 2008, investigators at the Cleveland Clinic published a retrospective study comparing outcomes after cardiac surgery for patients transfused with freshly collected red blood cells (RBCs; stored <2 weeks) versus old RBCs (stored >2 weeks).1 Transfusion with old RBCs was associated with more complications post-surgery and increased mortality. Since then, one of the major controversies in transfusion medicine has been whether a lesion develops during RBC storage, which could result in inferior recipient outcomes. This question has been addressed in more than ten reported trials, none of which have yielded data that show a significant advantage of fresh RBCs compared with old RBCs. A variety of patient populations have been studied (including intubated adults in the intensive care setting, general hospital patients, and neonates).2–6 However, whether the oldest RBCs, in their final week of storage, could be associated with increased risk of recipient morbidity or mortality, or both, compared to RBCs that were transfused within 1 week of collection has never been investigated. Because preliminary evidence suggests RBCs at the end of the current allowed storage period might cause harm,7–8 some stakeholders in transfusion medicine have even wondered whether it would be ethical to conduct a trial in which some patients are randomly assigned to transfusion with RBCs that have been stored for more than 35 days. In The Lancet Hematology, Cook and colleagues9 present the results of a secondary analysis of the INFORM trial data to investigate whether transfusion with RBCs after 35–42 days of storage was associated with worse outcomes than transfusion with RBCs that had been stored for less than a week. The INFORM trial was a ran domised controlled, multicentre, multinational trial of the effect of storage duration on patient in-hospital mortality.5 Importantly, the INFORM trial included more than 24 000 patients and was powered for mortality; this is far more patients than were enrolled in any other large trials, which cumulatively enrolled about 5000 patients.2,3 Of 24 726 patients included in the secondary analysis, 4480 (18%) patients were exposed to RBCs with longest www.thelancet.com/haematology Vol 4 November 2017
storage, 1392 (6%) patients were exposed exclusively to RBCs with shortest storage, and 18 854 (76%) patients were exposed to RBCs stored 8–35 days. The authors found equivalent risk for in-hospital death in patients who were transfused with RBCs stored for durations at either end of the storage range. In a multivariable model including patients of all blood types and adjusting for patient demographics, diagnosis, and blood product use, transfusion of RBCs stored for more than 35 days was not associated with increased mortality compared with transfusion of RBCs stored 7 days or less (hazard ratio 0·91, 95% CI 0·72–1·14; p=0·40). One limitation of this study is that individuals who received old RBCs did not exclusively receive RBCs that had been stored for longer than 35 days. However, the high number of patients involved in the INFORM study should be sufficient to quell worry that the study was insufficiently powered to detect a worrisome signal. The overall study finding is of substantial interest to the practice of transfusion medicine, as none of the previous clinical trials assessing the age of blood were able to compare outcomes for patients receiving RBCs at the extremes of storage life. In addition to their implications on patient care, the trial data will probably have regulatory importance. The transfusion medicine community has been concerned about the possibility of lesions developing in blood towards the end of allowed storage period. Some transfusions services in both the USA and Europe are already restricting the transfusion of the oldest RBCs.10 Additionally, transfusion specialists speculated that regulatory bodies would re-evaluate the licensed dating period of RBCs. The transfusion community has been anxiously asking questions about best practice, and these data presented by Cook and colleagues seem to have provided a definitive answer. Reassuringly, the findings are consistent with AABB’s recent transfusion guidelines,2 which state that “patients should receive RBC units selected at any point within their licensed dating period rather than limiting patients to transfusion of only fresh RBC units”.
Garo/Phanie/Science Photo Library
Finally, what we have been waiting for: evidence that transfusion of RBCs at the extreme of the storage spectrum is safe
Published Online October 9, 2017 http://dx.doi.org/10.1016/ S2352-3026(17)30179-5 See Articles page e544
e504
Comment
After so many studies, it seems that the transfusion medicine community can finally be reassured that patient outcomes are not meaningfully altered by transfusing RBCs that are approaching their 42-day outdate. Eric A Gehrie, *Aaron A R Tobian Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA [email protected] We declare no competing interests. 1 2 3
e505
Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med 2008; 358: 1229–39. Carson JL, Guyatt G, Heddle NM, et al. Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA 2016; 316: 2025–35. Alexander PE, Barty R, Fei Y, et al. Transfusion of fresher versus older red blood cells in hospitalized patients: a systematic review and meta-analysis. Blood 2016; 127: 400–10.
4
Kor DJ, Kashyap R, Weiskopf RB, et al. Fresh red blood cell transfusion and short-term pulmonary, immunologic, and coagulation status. Am J Respir Crit Care Med 2012; 185: 842–50. 5 Heddle NM, Cook RJ, Arnold DM, et al. Effect of short-term vs long-term blood storage on mortality after transfusion. N Engl J Med 2016; 375: 1937–45. 6 Fergusson DA, Bebert P, Hogan DL, et al. Effect of fresh red blood cell transfusions on clinica outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial. JAMA 2012; 308: 1443–51. 7 Rapido F, Brittenham GM, Bandyopadhyay S, et al. Prolonged red cell storage before transfusion increases extravascular hemolysis. J Clin Invest 2017; 127: 375–82. 8 Goel R, Johnson DJ, Scott AV, et al. Red blood cells stored 35 days or more are associated with adverse outcomes in high-risk patients. Transfusion 2016; 56: 1690–98. 9 Cook RJ, Heddle NM, Lee K-A, et al. Red blood cell storage duration and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial. Lancet Haematol 2017; published online Oct 9. http://dx.doi. org/10.1016/S2352-3026(17)30169-2. 10 Klein HG, Cortes-Puch I, Natanson C. More on the age of transfused red cells. N Engl J Med 2015; 373: 283.
www.thelancet.com/haematology Vol 4 November 2017