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AABB updates guidelines on red blood cell transfusion threshold, storage duration
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A restrictive red blood cell transfusion threshold is safe in most clinical settings, and current banking practices of using standard-issue blood should be continued, according to AABB’s 2016 red blood cell transfusion clinical practice guidelines.
AABB’s new guidelines included two primary recommendations. First, a restrictive red blood cell (RBC) transfusion threshold of 7 g/dL — rather than 10 g/dL — should be used for hospitalized, hemodynamically stable adults. Second, an 8 g/dL threshold is recommended for patients undergoing orthopedic or cardiac surgery, as well as for those with pre-existing cardiovascular disease.
“The original AABB RBC transfusion guidelines were released in 2012. Since then, several new studies have provided valuable data enabling us to update these evidence-based recommendations to address both RBC transfusion thresholds for broader patient populations and RBC storage duration,” Miriam A. Markowitz, CEO of AABB, said in a press release.
Jeffrey Carson, MD, internist at Robert Wood Johnson University Hospital, and colleagues evaluated data from 31 randomized clinical trials (n = 12,587) that compared restrictive thresholds — in which transfusion is not indicated until a person’s hemoglobin level is 7 g/dL to 8 g/dL — with liberal thresholds, or those around 9 g/dL to 10 g/dL. The number of patients in these studies represents a near doubling from the studies used to write the 2012 guidelines, Carson said in a press release.
Restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia or thromboembolism.
Because there did not appear to be harm associated with withholding transfusions, the guidelines give a strong recommendation for the restrictive threshold.
Carson and colleagues also assessed optimal RBC storage duration based on data from 13 randomized controlled trials composed of 5,515 participants who were randomly assigned to receive fresher blood (< 10 days) or standard-issue blood. The storage duration ranged from a median of 4 days (mean, 12.1 days) for fresher RBCs to a median of 19 days (mean, 28 days) for standard-issue RBCs.
“One of the biggest controversies regarding transfusions is whether older blood is harmful,” Aaron Tobian, MD, PhD, associate director of transfusion medicine and associate professor of pathology at Johns Hopkins Medicine, said in a release. “However, no previous guidelines have made any recommendations on the red blood cell storage duration.”
Results of this analysis showed fresher blood did not reduce mortality risk compared with standard-issue blood (RR = 1.04; 95% CI, 0.95-1.14).
Researchers noted trials have not assessed the effect of long-term RBC storage (near the 42-day expiration for RBC units stored with additive solution). Thus, how AABB’s recommendation applies to centers with RBCs stored for longer than 35 days is unknown.
“If data suggests no harm from the use of standard-issue blood and fresher blood would only constrain a limited resource, continuing with standard practice is appropriate,” Tobian said.
AABB’s new guidelines represent “an important update” to the recommendations of 2012, Mark H. Yazer, MD, associate professor of pathology at University of Pittsburgh Medical Center, and Darrell J. Triulzi, MD, director of the division of transfusion medicine in the department of pathology and medical director of the Institute for Transfusion Medicine at University of Pittsburgh Medical Center, wrote in an accompanying editorial.
“This recommendation reveals science as it should evolve; the hypothesis that the receipt of standard-issue RBC units could lead to higher morbidity and mortality was suggested by an observational study of patients undergoing cardiac surgery,” Yazer and colleagues wrote. “When this concept was tested in well-designed randomized clinical trials, the original hypothesis was shown not to be valid in patients undergoing cardiac surgery, critically ill patients or premature neonatal patients. Rather than the duration of storage, the indication for RBC transfusion remains the more pertinent clinical question. These new guidelines from the AABB represent medicine at its best in that they are evidence based.” – by Chuck Gormley
Disclosure: Carson and Tobian report no relevant financial disclosures. Please see the full guidelines for a list of all other researchers’ relevant financial disclosures. Triulzi reports grants from NHLBI and personal fees from Fresenius Kaboi. Yazer reports no relevant financial disclosures.
Perspective
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Jed B. Gorlin
In its salient perspective on the American Board of Internal Medicine Foundation’s Choosing Wisely campaign, Morden and colleagues noted that “participating societies generally name other specialists’ services as low value.” Specifically, medical specialists typically listed lower use of radiographic, medication or laboratory services as targets for savings.
It is, therefore, a tribute to the AABB — formerly known as American Association of Blood Banks — that its Choosing Wisely list includes patient blood management goals of transfusing at lower hemoglobin thresholds (restrictive transfusion) and transfusing fewer units at time.
The revision of the red blood cell clinical practice guidelines largely reflects the previous guidelines with respect to reinforcing the recommendation for restrictive guidelines — lower hemoglobin threshold as a transfusion trigger — and updates with a second recommendation that suggests using units independent of their storage age in light of data that failed to find any clinical outcomes benefit for transfusion of fresher units. With respect to the former recommendation, additional references were cited documenting that the restrictive trigger yielded identical outcomes in ICU, cardiac surgery, orthopedic surgery and sepsis clinical trials.
For the recommendation about storage age of red blood cells, most of the clinical studies have been completed and published in the last several years, and none showed an advantage of fresher units for the outcomes measured. Particularly impressive were studies of very fresh vs. maximum storage-age blood in treatment of pediatric patients with severe anemia secondary to malaria and high lactate levels. Both fresh and old blood were equally effective in raising hemoglobin level; further, both decreased lactate and improved cerebral oxygenation equally, illustrating that the older cells demonstrated identical physiologic benefit to the younger cells.
All of these studies were in standard volume and acute transfusion. These do not gainsay the advantages from using fresher units to minimize risk from hyperkalemia in very large-volume transfusions (eg, entire blood volume exchanges in hemolytic disease of the newborn, extracorporeal membrane oxygenation, pediatric cardiac surgery on bypass, etc). Nor does this impact the recommendations of the Guidelines for the Clinical Management of Thalassaemia for transfusion at a minimum hemoglobin of 10 g/dL and for use of blood less than 14 days old to mitigate against iron overload and to increase the time between transfusions for transfusion-dependent patients.
In short, this rigorous objective review of studies confirms the safety of both a more restrictive transfusion strategy and the use of blood throughout its storage age.
AABB. Five things physicians and patients should question. Available at: www.aabb.org/pbm/documents/choosing-wisely-five-things-physicians-and-patients-should-question.pdf. Accessed on Oct.28, 2016.
Cappellini MD, et al. Guidelines for the clinical management of thalassaemia [Internet]. 2nd revised edition. Thalassaemia International Federation. 2008. Available at: www.ncbi.nlm.nih.gov/books/NBK173967. Accessed on Oct. 28, 2016.
Morden NE, et al. N Engl J Med. 2014;doi:10.1056/NEJMp1314965.
Disclosure: Gorlin reports no relevant financial disclosures.
Christopher C. Silliman
The AABB published its clinical practice guidelines on red blood cell transfusion thresholds and storage. All available randomized control trials designed to evaluate hemoglobin thresholds (31 trials) and red blood cell storage duration (13 trials) were included, and the results were summarized by the Grading of Recommendations Assessment, Development and Evaluation method.
In short, a restrictive transfusion threshold — hemoglobin less than 7 g/dL — was recommended for all hemodynamically stable adults, even the critically ill. A similar restrictive transfusion threshold of hemoglobin less than 8 g/dL is recommended for patients undergoing orthopedic or cardiac surgery and those with preexisting cardiovascular disease, although hemoglobin of 7 g/dL vs. 8 g/dL likely is comparable.
These recommendations do not apply to patients with coronary artery syndrome, severe thrombocytopenia or transfusion-dependent chronic anemia. With respect to storage, all patients — even neonates — should be given red blood cells of any age within their licensed dating period.
The literature on red blood cell transfusion is heterogeneous, and much has changed with respect to red blood cell storage over the decades the randomized controlled trials encompass (1948 to 2016). With regard to transfusion triggers, trauma surgeons use a significant amount of the blood supply, and it is unlikely that a randomized controlled trial will be done for injured patients. Most centers have adopted restrictive red blood cell transfusion strategies (hemoglobin, 7 g/dL) because decreasing red blood cell transfusions in the first 12 hours — along with other improvements in trauma surgery and management — decreased the incidence, severity and mortality related to postinjury multiple organ failure, the leading cause of in-hospital mortality.
In addition, trauma patients likely receive the older stored units, and randomized controlled trials are virtually impossible. Given the data, which controlled for the number of units transfused and concluded that older units were associated with the development of multiple organ failure, a hemoglobin trigger of 7 g/dL has been largely accepted.
The finding that transfusion of standard-issue red blood cells is no different from fresh red blood cells is not surprising given the age of red blood cells in the standard-issue arms of these randomized controlled trials, and it is not likely that the oldest units (days 35 to 42) will ever be studied. Moreover, data using red blood cells stored for 40 to 42 days support 35 days of age as a reasonable licensed outdate rather than 42 days. Despite these limitations, the AABB recommendations with regard to transfusion triggers are appropriate, and better-quality stored red blood cells will obviate the deleterious effects of storage, which require more study.
Carson JL, et al. JAMA. 2016;doi:10.1001/jama.2016.9185.
Ciesla DJ, et al. Arch Surg. 2005;140:432-438.
Hod EA, et al. Transfusion. 2011;doi:10.1111/j.1537-2995.2011.03096.x.
Hod EA, et al. Transfus Clin Biol. 2012;doi:10.1016/j.tracli.2012.04.001.
Zallen G, et al. Am J. Surg. 1999;178:570-572.
Disclosure: Silliman reports no relevant financial disclosures.
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