2025 AABB国际临床实践指南：红细胞输注在急性心肌梗死中的应用

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AABB Guideline on Red Cell Transfusion in Acute Myocardial Infarction

trial(6) and the REALITY(Restrictive and Liberal Transfusion Strategies in Patients with AMI) trial(7)-that tested the effect of RBC transfusion based on 2 different Hb thresholds on patient-important AMI outcomes.Although the designs of both trials were similar, they reported different directions of effect for key outcomes.It is therefore timely to review the current literature examining RBC transfusion thresholds in patients with AMI and provide recommendations.

# METHODS FOR GUIDELINE DEVELOPMENT PROCESS

This work followed recognized standards for GRADE(Grading of Recommendations Assessment,Development and Evaluation) methods to summarize evidence and formulate recommendations(8, 9).

# Steering Committee and Panel Composition and Conflicts

The Steering Committee(S.J.S., M.B.P., J.D., and G.H.G.) planned analyses, presentation of evidence,and the process of moving from evidence to recom-mendation. The AABB, through its Clinical Transfusion Medicine Committee, commissioned in high guideline in March 2024 and recruited all participants from a previ-ous panel as well as experts representing relevant inter-national organizations(Appendix, available at Annals.org). The Steering Committee began the meta-analysis in April 2024, and the panel first met virtually in June 2024 to finalize the PICO(population, intervention, com-parator, and outcome) question and define minimal important differences(MIDs) and relevant outcomes of interest. The panel reviewed the results of the meta-analysis and drafted recommendations in September 2024. The guideline manuscript was finalized in February 2025. The international panel included members with relevant multidisciplinary expertise(including cardiol-ogy, critical care, hematology, transfusion medicine,anesthesiology, and internal medicine), 2 patient part-ners(A.D. and N.H.S.), and 2 methodologists(J.D. and G.H.G.). Individual members disclosed potential finan-cial, professional, or personal conflicts of interest. Primary investigators on trials(J.L.C. and P.G.S.) provided their perspectives to the guideline panel but recused them-selves from voting on recommendations. The vote on the final recommendation was anonymous; 3 members of the panel did not support a recommendation for a liberal strategy, and in the final vote, the majority(70%) of the panel voted for a recommendation of an Hb concentra-tion below 10 g/dL versus a range of 9 to 10 g/dL.

Scope: PICO Question

The PICO question was as follows: For hospital-ized patients with AMI, should RBC transfusion be ini-tiated with an Hb threshold of 7 to 8 g/dL or an Hb threshold of less than 9 to 10 g/dL?

Given that the trials enrolled only patients with AMI,we provide recommendations solely for this patient

population. The panel recognizes that transfusion deci-sions are more challenging in patients with hemody-namic instability in whom there is pulmonary edema and volume overload and/or oxygen supply-demand mismatch without volume overload. Although the for-mer responds to diuresis, the latter may respond to RBC transfusion. Therefore, the panel's recommen-dation applies only to those without hemodynamic instability.

Perspective

This guideline's primary perspective is that of the patient, including medical, financial, and psychological effects, as opposed to that of the health care system(10). Given that the global blood supply is a limited and costly resource, the panel also considered second-ary public health issues that are relevant for the global blood supply.

# Values and Preferences Underlying the Recommendation

The values and preferences underlying the recom-mendation reflect the life-threatening context of AMI and include mortality and reduction of the risk for recurrent MI(high value), severe adverse events after RBC transfusions(high value), and conservation of the RBC supply(moderate value). Overall, the panel places a higher value on the uncertain potential benefits of a liberal strategy on reducing mortality than the unequiv-ocal benefits of a restrictive strategy in conserving RBC units and reducing transfusion-related severe adverse events.

Outcomes and MID

To rate the importance of outcomes of interest(Supplement Table 1, available at Annals.org) and identify what patients with AMI might consider as a threshold of MID for benefit or harm in important out-comes(30-day all-cause mortality, recurrent M1, trans-fusion-related severe events, stroke, and acute heart failure)(Supplement Table 2, available at Annals.org), the panel members completed surveys that reflected their opinions on what patients might value.These surveys established MIDs for 30-day mortality and severe adverse events. The Steering Committee extrapolated survey results to propose MIDs for recurrent Ml, stroke, and congestive heart failure that the panel reviewed and adopted(Supplement Table 3, available at Annals.org). Panels defined transfusion-related severe adverse events as events associated with respiratory and circulatory symptoms. The MINT investigators classified these events as anaphylaxis, transfusion-associated circu-latory overload(TACO), and transfusion-related acute lung injury(TRAL), whereas the REALITY investigators used categories of anaphylaxis, acute respiratory dis-tress syndrome, and acute heart failure.

Comments and Modification

The Steering Committee prepared the initial manu-script drafts. Authors, including international partners,

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reviewed and edited drafts and approved the final manuscript. The AABB Board of Directors provided a final review and approval.

Evidence Review and Rating Systematic Review

The panel developed this recommendation on the basis of a systematic review of the relevant evidence(11). We identified 4 trials that met eligibility criteria,based on repeated searches through April 2024. The meta-analysis focused the primary analysis on RCTs of patients presenting with AMI who were assigned to 2 different transfusion strategies (restrictive or liberal)based on Hb concentrations or hematocrit levels before receipt of a transfusion. Randomly assigned patients in the trials were excluded from the present analysis if they did not have AMI. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool, in which assessments are undertaken by outcomes (12).

We performed meta-analyses according to stand-ard Cochrane methods, with 2 key deviations from the methods used in the original review(11). We used a fixed-effects model rather than a random-effects model given the focused nature of our commission. For the purposes of the analysis, we also took the approach of considering the liberal threshold strategy as the inter-vention and the restrictive strategy as standard practice,as this is now the case in clinical practice. Therefore, we inverted previous data entry and presentation as used in the Cochrane review(11), and the GRADE Summary of Findings table presented here now considers judg-ments based on an assessment of the appropriateness of increasing the recommended threshold.

Analysis

All analyses were performed using Cochrane Review Manager 5(13). Risk ratios(RRs) and odds ratios(ORs)with 95% Cls were calculated using fixed-effects models(Mantel-Haenszel approach) for most outcomes; for those where events were rare(for example, expected at≤1%),we used the Peto OR. Absolute risk differences were cal-culated by applying ORs to estimated baseline risks(14).

Grading the Certainty of the Evidence and Formulating Recommendations

GRADE guidance informed overall risk of bias, impre-cision,indirectness,and inconsistency judgments(15).We summarized evidence using GRADE Summary of Findings tables(16), including judgments regarding evidence certainty, and the panel formulated recom-mendations using the GRADE evidence-to-decision framework(17).

RESULTS

Recommendation

For hospitalized patients with AMI, the international panel suggests RBC transfusion when the Hb is less than 10 g/dL(conditional recommendation, low-certainty evidence).

Good Practice Statement

For hospitalized adult patients with AMI, it is impor-tant to incorporate the clinical context(e.g., patients'history, signs, symptoms, hemodynamic status) and patients' preferences when weighing RBC transfusion decisions.

Remark

In accordance with the increased risks of severe adverse events in the liberal transfusion strategy, clini-cians should consider strategies for mitigation of adverse transfusion events. Strategies include optimizing fluid sta-tus peri-transfusion, slowing transfusion rate, prescribing diuretics, achieving the target Hb more gradually, and transfusing during renal replacement therapy sessions for renal failure.

Evidence Summary

The analysis identified and considered 4 eligible trials enrolling 4311 participants(Table 1). The MINT trial enrolled 3504 participants, and the REALITY trial included 666 participants(6, 7). A study by Carson and colleagues(18) was a pilot trial with 110 partici-pants(14 without AMI who are not included in the cur-rent analysis), and a study by Cooper and colleagues(19) was a single-institution trial that included 45 par-ticipants with AMI; both of these trials stopped before achieving their initial recruitment targets. Scrutiny of trial registers, including the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov, revealed no registered work that was eligible but unpublished.

Study outcomes were assessed as having low risk of bias or some concerns overall; no individual trial was rated as having high risk of bias for any domain for any outcome(Supplement Figure 1, available at Annals.org). Results of the meta-analysis of included outcomes are presented in Supplement Figure 2(avail-able at Annals.org).

Table 2 presents the summary of findings for com-parison of restrictive versus liberal transfusion strategies in patients with AMI for outcomes of 30-day mortality,recurrent M1, congestive heart failure, serious adverse events, stroke, acute kidney injury, and exposure to transfusion. A liberal transfusion strategy resulted in approximately 3.5 times more transfusions, with 34% of patients in the restrictive groups and 96% in the liberal groups receiving any transfusion(high certainty).

All 4 trials(n= 4311) evaluated 30-day mortality,with a pooled RR of 0.87(95% CI, 0.72 to 1.06). The absolute risk difference estimate between transfusion strategies indicated 1.2% fewer deaths with a liberal strategy. This estimate surpassed the panel-defined MID of 1%.

The MINT trial reported a high rate of recurrent M1 at 30 days in both groups(7.2% in the liberal group and 8.5% in the restrictive group), more than double the rate reported in the REALITY trial(3.1% in the lib-eral group and 2.1% in the restrictive group), with a

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Table 1. Clinical Trials That Included Patients With AMI

|Study,Year (Reference)|Design|Baseline Characteristics (Restrictive Group vs. Liberal Group)|Therapeutic Intervention (Restrictive Group vs. Liberal Group)|Thresholds (Restrictive Group vs. Liberal Group)|Primary Outcome|Main Results (Restrictive Group vs. Liberal Group)|Methodological Considerations| |---|---|---|---|---|---|---|---| |Cooper et al, 2011(19)|RCT,2 sites Enrollment: 2003-2009 Follow-up:30 d|STEMI:46% vs. 33% NSTEMI:54% vs. 67% Transfusion before ran-domization not reported|PCI: 54% vs. 57%|Hematocrit level <24%(n= 21) Hematocrit level <30%(n= 24)|In-hospital death Recurrent MI CHF|30-day mortal-ity:8.3% vs. 4.8% AMI:0% vs. 4.8% CHF:12.5% vs. 42.8% Serious AEs: None|Small sample size Pilot Potentially important imbalances at baseline| |Carson et al, 2013(18)|RCT,8 sites, pilot Enrollment: 2010-2012 Follow-up:6 mo|STEMI:29.1% vs.30.9% NSTEMI:47.3% vs.38.2% Transfusion before ran-domization not reported|PCI:47.3% vs. 63.6% Hb concentra- tion<10 g/dL (n=55) Hb concentra- tion<10 g/dL (n=55)|Hb concentra- tion<8 g/dL (n=55) Hb concentra- tion<10 g/dL (n=342) Hb concentra- tion<10 g/dL (n=324)|Death Recurrent MI Unscheduled cur- Tzation|30-day mortal-ity:12% vs. 2.2% AMI:14% vs. 10.9% CHF:12% vs. 4.3% Serious AEs: None|Small sample size Pilot Not all patients had AMI (although data used here are only from those with AMI) Some imbalances at baseline Myocardial infarction and heart failure were centrally adjudicated All elements of the pri- many efficacy out-come, including Ml as well as acute heart failure, were centrally adjudicated| |Ducrocq et al, 2021(7) (REALITY)|RCT,35 sites,2 countries, noninferiority Enrollment: 2016-2019 Follow-up:1y|NSTEMI:68.4% vs.71.3% Transfusion before ran-domization not allowed|PCI:58.8% vs. 59.3% Hb concentra- tion<10 g/dL (n=324)|Hb concentra- 力 adverse 30-day mortal- ity:5.6% vs. 1.3% CHF:3.2% vs. 3.7% Serious AEs: 4.4% vs. 5.9%|30-day mortal- ity:5.6% vs. 3.1% CHF:3.2% vs. 3.7% Serious AEs: 4.4% vs. 5.9%|All elements of the pri many efficacy out-come, including Ml as well as acute heart failure, were centrally adjudicated Low rate of protocol dis- continuation(4.4% [restrictive] vs.0.6% [liberal]) No statistical analysis was performed for secondary outcomes, including type 1 and type 2 Ml, given the potential for type I error Unclear acute kidney failure and adverse events classifications, which were local site decisions and, except for acute heart failure, were not centrally adjudicated|| |Carson et al, 2023(6) (MINT)|RCT,144 sites, 6 countries, open-label, phase 3 Enrollment: 2017-2023 Follow-up:6 mo|NSTEMI:81.8% vs.80.8% Type 1 M1: 41.7% vs. 41.6% Type 2 M1: 55.3% vs. 56.3% Transfusion before ran- domization: 34.2% vs. 36.4%|PCI:29.1% vs. 28.1%|Hb concentra- tion<8 g/dL permitted <7 g/dL strongly rec- ommended (n=1749) Hb concentra- tion<10 g/dL (n=1755)|30-day mortal-ity:9.9% vs. 8.5% AMI:8.5% vs. 7.2% CHF:5.8% vs.6.3% Serious AEs: 0.6% vs.2%|Myocardial infarction was the only trial out- come that was cen- trally adjudicated of transfusions before randomization Imbalance of rates protocol discontinua-tion(2.6%[restrictive] vs.13.7%[liberal]) Cardiac deaths as an additional outcome were not centrally adjudicated||

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|Table 1-Continued|Table 1-Continued|Table 1-Continued|Table 1-Continued|Table 1-Continued|Table 1-Continued|Table 1-Continued|Table 1-Continued| |---|---|---|---|---|---|---|---| |Study, Year (Reference)|Design|Baseline Characteristics (Restrictive Group vs. Liberal Group)|Therapeutic Restrictive Group vs. Liberal Group)|Thresholds (Restrictive Group vs. Liberal Group)|Primary Outcome|Main Results (Restrictive Group vs. Liberal Group)|Methodological Considerations| ||||||||MINT investigators stated that subgroup analysis was not adjusted for multiplic-ity. The observed dif-ferences for type 1 and type 2 MI might be explained by chance(P for interac- tion= 0.16)(28).| |||||||Unclear adverse events classification, which was a local site deci- sion and was not cen-trally adjudicated||

AE= adverse event; AMI= acute myocardial infarction; CHF= congestive heart failure; Hb= hemoglobin; Ml= myocardial infarction; MINT=Myocard lshemia and Transfusion; NSTEMI= non-ST-segment elevation myocardial infarction; PCI= percutaneous coronary intervention;RCT= randomized controlled trial; REALITY= Restrictive and Liberal Transfusion Strategies in Patients with AMI; STEMI= ST-segment elevation myocardial infarction.

pooled RR of 0.88(CI, 0.71 to 1.09). The absolute dif-ference in recurrent MI between transfusion strategies was 0.9%, indicating moderate certainty of little or no difference given the panel-defined MID of 2%.

Two trials described severe adverse events, although definitions varied. The REALITY trial reported incidence of acute lung injury of 2.2%, whereas the MINT trial reported incidence of 0.3%. These rates are higher than those reported in the general hospital population,with reported pooled TRALI estimates for active surveil-lance studies of approximately 0.17 (CI, 0.03 to 0.43)cases per 10000 persons for RBCs(20,21).The pooled OR was 2.21 CI,1.42 to 3.45) for severe adverse events,with higher rates in the liberal group(2 trials; n= 4170).The absolute difference between transfusion strategies was 1.4%, with low certainty of little or no effect given the panel-defined MID of 2.5%.

There were no apparent differences between trans-fusion strategies for other outcomes, including conges-tive heart failure, stroke, and acute kidney injury.

Rationale for the Recommendation

The 1.2% overall estimated benefit in 30-day mor-tality exceeded the panel-defined MID, supporting the potential benefit of a liberal transfusion strategy.Moreover, there was moderate-certainty evidence that the liberal strategy does not result in an important increase in mortality. A higher incidence of transfusion-related adverse events in the liberal group, in which transfusion was almost universal and participants received 3 times more units compared with the restric-tive group, might be expected, although the difference between strategies was less than the panel's chosen MID. Given that the panel's perspective of considering value and preferences placed higher value on the uncertain potential benefits of a liberal strategy in

reducing mortality rather than the unequivocal benefits of a restrictive strategy in conserving RBC units and reducing transfusion-related severe adverse events,the panel agreed on a conditional recommendation in favor of the higher threshold.

Clinical Considerations

- This guideline evaluated the optimal Hb threshold for RBC transfusion in patients with AMI and provides a conditional recommendation to use a liberal trans-fusion threshold.

As with any medical intervention, risks and benefits should be weighed before deciding whether to pro-ceed with a transfusion.

● A liberal threshold up to 10 g/dL might not apply to all patients with AMI, and current evidence does not allow for identification of patients with AMI who would benefit the most from a liberal threshold.

● There are almost no clinical scenarios that would pre-clude transfusions except very rare situations of near fatal anaphylactic or hemolytic reactions or impossi-bility of finding compatible blood. Blood availability might be a limiting factor in some geographic areas.

● The panel considered the importance of implement-ing appropriate risk mitigation strategies in patients at risk for severe reactions, such as those with circulatory overload. These approaches include but are not limited to the following: 1) risk stratifica-tion for TACO, 2) optimizing fluid status in the peri-transfusion period, 3) slowing the RBC infusion rate,4) peri-transfusion diuresis, 5) achieving the target Hb concentration more slowly, and 6) transfusing during renal replacement therapy for patients acutely or chronically requiring such therapy(22).

● Due to the higher risk for serious adverse events associ-ated with the suggested transfusion strategy, clinicians

AABB Guideline on Red Cell Transfusion in Acute Myocardial Infarction

Table 2. Summary of Findings Table for a Liberal Threshold Compared With a Restrictive Threshold for Guiding Red Blood Cell Transfusion

|Outcome|Patients (Trials),n|Relative Effect (95% CI)|Absolute Effects|Absolute Effects|Certainty|Plain Language| |---|---|---|---|---|---|---| |Outcome|Patients (Trials),n|Relative Effect (95% CI)|Restrictive Threshold|Liberal Threshold|Certainty|Plain Language| |30-day mortality|4311(4 trials)|RR,0.87(0.72 to 1.06)|93 per 1000|81 per 1000|12 fewer per 1000(26 fewer to 6 more)|$\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplus$ $\oplu|

MID= minimal important difference; OR=odds ratio; RR=risk ratio.

* We have rated down for inconsistency( $I^{2}$ of 39%, with the 2 largest trials differing) and imprecision when considering a potential decrease in mortality.

$\dagger$ When considering the potential for an increase in mortality, we have rated down for inconsistency but not for imprecision, being mindful of the MID set at 1%.

We have rated down for imprecision because with an MID of 2%, the Cl includes both an important effect and an unimportant effect.$$\text{ We have rated down for important inconsistency}(\text{ I}^{2}\text{ of} 70\%\text{ between} 2\text{ large trials}[1,2]\text{) and because the Cl includes both an important effect}.$$an unimportant effect.

should personalize each transfusion decision and informed consent discussion.

● Clinicians should adopt general approaches to miti-gate the risk for anemia through the deployment of patient blood management strategies, including mini-mizing unnecessary blood testing, use of low-volume sample collection tubes, and early recognition and treatment of underlying causes of anemia.

Outcomes of Interest

The panel considered the evidence from 4 trials,recognizing that most of the data were derived from the MINT trial(86% weight for the 30-day mortality

meta-analysis). The MINT and REALITY trials were rated at low risk of bias for the key outcomes, and the 1.2% overall estimated benefit in 30-day mortality exceeded the panel-defined MID. The results provided moderate-certainty evidence that the liberal strategy does not result in an important increase in mortality,and there was no compelling evidence of important harm for other outcomes based on the panel-defined MIDs.

The MINT trial suggested reduced mortality with the liberal strategy, whereas the REALITY trial suggested increased mortality. It is possible, given the wide Cls for individual trials, that these differences represent a chance

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finding. Indeed, the Cls for the REALITY trial include the point estimate from the MINT trial, supporting this possibility, and an interaction test for subgroup differ-ences was consistent with chance as an explanation of the difference( $\chi^{2}=2.55$ ; degrees of freedom=1[P=0.11])(Supplement Figure 3, available at Annals.org).Nevertheless, the panel believed that the differences were large enough to rate down the certainty of evi-dence for inconsistency. Although one might speculate on possible explanations for differences in the main outcomes between both trials(inclusion criteria, type of AMI, proportion undergoing percutaneous coronary intervention, mortality rate, transfusion protocol), chance is a possible explanation.

Benefits and Harms

In patients with AMI, the relative safety of restrictive Hb thresholds as commonly recommended in many populations has been unclear. Reflecting the tension between benefit and risk, some panel members were not confident that the desirable effects of RBC trans-fusion outweighed all of the undesirable effects in all patients with AMI. The panel then discussed whether the recommendation should adopt an Hb threshold of 10 g/dL, which was evaluated in 3 of the 4 trials, or a threshold range of 9 to 10 g/dL, which some clinicians on the panel believed was appropriate. Although a sec-ondary analysis of the MINT trial raised the hypothesis of an increase in mortality tied to each 1-g/dL decrease in the Hb threshold, the Cls were wide, indicating impreci-sion(23). A restrictive strategy may result in increased mortality in patients with AMI. Overall, the panel pro-vided a conditional recommendation based on low-certainty evidence for a liberal transfusion strategy using an Hb threshold of less than 10 g/dL for patients with AMI.

Strengths and Weaknesses

The results of our analysis are consistent with recent systematic reviews(24, 25), findings in a recent large population-based study(26), and a guideline on criti-cal illness(27). By comparison, few interventions in AMI have shown mortality benefits of more than 1%,including use of percutaneous coronary intervention versus thrombolytic therapy(28).

A strength of this guideline is the application of robust GRADE methods, including use of a multipro-fessional panel of clinicians who are engaged across the spectrum of activities relevant to the care of patients with AMI. The data used to inform the recommendations were from large trials that generated current data reflect-ing modern practice. Limitations of our work include MID estimates based on limited direct evidence regard-ing patient values and preferences(Supplement Table 3). The guideline recommendation does not apply to patients with acute coronary syndrome or patients without AMI, for whom uncertainty about the safety of restrictive thresholds remains.

Research Gaps

The panel identified several research needs. The liberal transfusion group in both the MINT and REALITY trials applied an Hb threshold of 10 g/dL,but the optimal approach to achieve the most appro-priate balance between favorable and unfavorable consequences of RBC transfusion in different AMI populations remains unclear. In the MINT trial, death or recurrent Ml at 30 days was more frequent in patients with type 1 Ml(atherothrombotic plaque rupture or ero-sion) who were randomly assigned to the restrictive transfusion strategy compared with the liberal strategy(29). The REALITY trial reported a higher rate of recur-rence of AMI in the restrictive group.

Clinically, the benefits and harms of RBC transfu-sion are likely to vary according to the severity and extent of coronary artery disease and the severity of ventricular impairment after AMI. Benefit might be con-sidered more likely where coronary revascularization is not possible or is incomplete. Persons with residual ob-structive disease, particularly where this subtends a large territory or multiple territories, might be at greater risk for recurrent myocardial ischemia, which may be exacer-bated by anemia. In contrast, harm might be more likely in those with significant new ventricular impairment or cardiogenic shock after AMI, where transfusion could contribute to volume overload and acute pulmonary edema.Therefore, to identify patients who might bene-fit more and to personalize the transfusion decision,future research should address the optimal threshold for transfusion according to the mechanism of Ml and patient-specific characteristics.

In conclusion, this guideline supports the potential benefit of a liberal transfusion strategy, with a condi-tional recommendation for an RBC transfusion strat-egy based on an Hb concentration less than 10 g/dL in patients with AMI.

From Department of Laboratory Medicine and Pathology,Department of Medicine, University of Washington, Seattle,Washington(M.B.P.); Radcliffe Department of Medicine,University of Oxford, and Department of Transfusion Medicine,NHS Blood and Transplant, Oxford, United Kingdom, and International Collaboration for Transfusion Medicine Guidelines(ICTMG), Canada(S.J.S.); Musculoskeletal Research Unit,Southmead Hospital, University of Bristol, Bristol, United Kingdom(J.D.); Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California(S.B.);Department of Pathology and Molecular Medicine, Kingston Health Sciences Centre and Queen's University, Kingston, Ontario, Canada(J.C.); Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey(J-L.C.); Department of Laboratory Medicine and Pathology,University of Minnesota, Minneapolis, Minnesota(C.S.C., N.D.Z.);Patient Partner, Salt Lake City, Utah(A.D.); Department of Pathology and Minnesota, Minneapolis, Washington University School of Medicine in St. Louis, St. Louis, Missouri(B.J.G.); Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering

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Cancer Center, New York, New York(G.K.G.); Departments of Anesthesiology and Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin(A.S.H.); Department of Pathology,New York University Grossman School of Medicine,New NYC Health+ Hospitals/Bellevue, New York, New York(J-L.J.); Department of Surgery, Division of Trauma, Surgical Critical Care and Surgical Emergencies, Perelman School of Medicine,University of Pennsylvania, Philadelphia, Pennsylvania(L-J.K.);University Health Network, Sinai Health, and Women's College Hospital Senior Scientist, Toronto, Ontario, Canada(K.K.); Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada(Y.L.); Department of Pathology, University of Utah, Salt Lake City, Utah(RAM.);Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia, and Department of Anesthesia, Austin Health, Heidelberg, Victoria, Australia(L.F.M.);BHF Centre for Cardiovascular Science, University of Edinburgh,and Usher Institute, University of Edinburgh, Edinburgh, United Kingdom(N.L.M.); Pathology Associates of Albuquerque, Albuquerque, New Mexico(C.H.M.); Department of Laboratory Medicine and Pathobiology, University of Toronto and St. Michael's Hospital-Unity Health Toronto, Toronto, Ontario, Canada, and International Collaboration for Transfusion Medicine Guidelines(ICTMG), Canada(K.P.); Department of Medicine, University of Chicago, Chicago, Illinois(M.T.P.); Department of Pathology and Laboratory Medicine, The Robert Lamer, M.D. College of Medicine at The University of Vermont and The University of Vermont Medical Center, Burlington, Vermont(J.S.R.); Department of Pathology and Laboratory Medicine, UT Health San Antonio, San Antonio, Texas(E.S.); Department of Laboratory Medicine and Pathology, Seattle Children's Hospital and University of Washington, Seattle,Washington(N.H.S.); Department of Internal Medicine, Division of Cardiovascular Medicine, University of Utah, Salt Lake City,Utah(K.S.); University Paris-Cité,INSERM_U1148, and Assistance Publique-Hopitaux de Paris, French Alliance for Cardiovascular Trials, Paris, France(P.G.S.); Department of Pathology, Johns Hopkins University, Baltimore, Maryland(A.A.R.T.); Department of Unit Transfusion Medicine (UTG), Sanquin Blood Bank,Amsterdam, the Netherlands, and Department of Hematology,Erasmus Medical Center, Rotterdam, the Netherlands and Kingdom(T.W.); Department of Anesthesiology and Perioperative Medicine,University of Pittsburgh, Pittsburgh, Pennsylvania(J.W.); Department of Haematology, Monash Health, Monash University School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia(E.M.W.); and Departments of Clinical Epidemiology and Biostatistics and Medicine, McMaster University, Hamilton, Ontario, Canada(G.H.G.)

Financial Support: Support for guidance in guideline development was pro-vided by the Association for the Advancement of Blood&Biotherapies, Bethesda, Maryland.

Disclosures: Disclosure forms are available with the article online.

Corresponding Authors: Monica B. Pagano, MD, Professor,Laboratory Medicine and Pathology, University of Washington,

8 Annals of Internal Medicine

$$\text{ Box 357110, 1959 NE Pacific Street, Seattle, WA 98195(e-mail,}$$monibea@uw.edu); Simon J. Stanworth, MD, DPhil, NHS Blood and Transplant, John Radcliffe Hospital, Headley Way,Headington,Oxford OX3 9BQ, United Kingdom(e-mail, simon.stanworth@nhst.nhs.uk).

Author contributions are available at Annals.org.

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Author Contributions: Conception and design: M.B. Pagano,S.J.Stanworth,J.Dennis,G.H.Guyatt.

Analysis and interpretation of the data: M.B. Pagano, S.J.Stanworth, J. Dennis, S. Bakhtary, J. Callum, J.L. Carson, C.S.Cohn, A. Dubon, B.J. Grossman, A.S. Hess, J.L. Jacobson, L.J.Kaplan, Y. Lin, R.A. Metcalf, L.F. Miles, N.L. Mills, K. Pavenski, M.T. Prochaska, J.S. Raval, T. Walsh, J. Waters, N.D. Zantek, G.H.Guyatt.

Drafting of the article: M.B. Pagano, S.J. Stanworth, J. L. Carson, A. Dubon, B.J. Grossman, A.S. Hess, L.J. Kaplan, N.L. Mills, C.H.Murphy, J. Waters.

Critical revision for important intellectual content: M.B. Pagano,S.J. Stanworth, J. Callum, J.L. Carson, B.J. Grossman, A.S. Hess, L.J. Kaplan, K. Karkouti, Y. Lin, R.A. Metcalf, L.F. Miles, N.L. Mills, C.H. Murphy, T.J. Mcshang, A.S. Beral, S.J. Zhu, A.R. S. Berg, S.J. Zhu, A.R. Tobian, C. So-Osman,T.Walsh,J.Waters,E.M.Wood.

Final approval of the article: M.B. Pagano, S.J. Stanworth,J. Dennis, S. Bakhtary, J. Callum, J.L. Carson, C.S. Cohn,A. Dubon, B.J. Grossman, G.K. Gupta, A.S. Hess, J.L. Jacobson,L.J.Kaplan,K.Karkouti,Y.Lin,R.A.Metcalf,L.F.Miles,N.L.Mills,C.H. Murphy,K. Pavenski, M.T. Prochaska,J.S.Raval,E.Salazar,N.H. Saifee, K. Shah, P.G. Steg, A.A.R. Tobian, C. So-Osman,T.Walsh,J.Waters,E.M.Wood,N.D.Zantek,G.H.Guyatt.

Administrative, technical, or logistic support: J. Dennis, C.S.Cohn,E.M.Wood.

Collection and assembly of data: M.B. Pagano, S.J. Stanworth,J.Dennis,J.L.Carson,P.G.Steg,J.Waters.

APPENDIX: ADDITIONAL CONTRIBUTIONS

Steering Committee

Members of the Steering Committee were Monica B. Pagano, MD; Simon J. Stanworth, MD, DPhil; Jane Dennis, PhD; and Gordon H. Guyatt, MD.

Panel and Guideline Group Members

The panel included current or former members of the AABB Clinical Transfusion Medicine Committee(Jeffrey L.Carson,MD; Monica B. Pagano, MD; Sara Bakhtary,MD; Claudia S. Cohn, MD, PhD; Brenda J. Grossman,MD, MPH; Gaurav K. Gupta, MD; Aaron S. Hess, MD,PhD; Jessica L. Jacobson, MD; Ryan A. Metcalf, MD; Colin H. Murphy, MD; Micah T. Prochaska, MD; Jay S. Raval, MD; Eric Salazar, MD; PhD; Nabiha H. Saifee, MD, PhD; Aaron A.R. Tobian, MD, PhD; Jonathan Waters, MD; and Nicole D.Zantek, MD, PhD) and the fol-lowing international organizations: the International Society of Blood Transfusion(Erica M. Wood, MD), the International Collaboration for Transfusion Medicine Guidelines(Katerina Pavenski, MD), the Society of Critical Care Medicine(Lewis J. Kaplan, MD), the European Hematology Association(Cynthia So-Osman,MD, PhD), the Society for the Advancement of Patient Blood Management(Jonathan Waters, MD), and the Society of Hospital Medicine(Micah T. Prochaska, MD).