A “restrictive” red blood cell transfusion threshold, a hemoglobin concentration <7 to 8 g/dL, has long been recommended for most hospitalized patients including anemic patients with stable cardiovascular disease (CVD). Although no threshold recommendation is given for acute coronary syndromes (ACSs), recent evidence suggests that “liberal” rather than “restrictive” transfusion strategies are associated with significantly improved safety for hospitalized patients with stable CVD and/or ACS. This finding suggests that previously available data were misinterpreted. Conclusions drawn from earlier transfusion trigger trials have been confounded by unintentional trial design and analysis flaws that have contributed to erroneous recommendations regarding the safety of a restrictive threshold. Subsequently, these conclusions have been incorporated into widely accepted guidelines and clinical practice. Management with a restrictive vs liberal transfusion strategy (<10 g/dL) increases the risk of new-onset ACS in patients with CVD by ∼2%. We estimate that since 2019, using hospital databases and a recent meta-analysis, this practice may have resulted in ∼700 excess ACS events per year in orthopedic surgical patients. Given these findings, transfusion practices in other clinical conditions, particularly those derived from similar transfusion trigger trials, should be questioned. Restrictive and liberal transfusion policies merit a general reconsideration. Rather than a single numerical transfusion trigger, transfusion therapy should be personalized. Consideration of an individual patient’s age, clinical status, and comorbidities is integral to transfusing. To avoid making similar errors, future trials of transfusion therapy should determine common practices before study inception and incorporate them as a usual-care “control” comparator arm into the trial design. Such studies should more reliably improve current transfusion practice.
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PERSPECTIVE|
November 14, 2024
Hemoglobin-based transfusion strategies for cardiovascular and other diseases: restrictive, liberal, or neither?
Clinical Trials & Observations
Charles Natanson,
Charles Natanson
1Critical Care Medicine Department, Clinical Center, and National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
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Willard N. Applefeld,
Willard N. Applefeld
2Division of Cardiology, Duke University Medical Center, Durham, NC
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Harvey G. Klein
Harvey G. Klein
3Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
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Blood (2024) 144 (20): 2075–2082.
Article history
Submitted:
June 27, 2024
Accepted:
September 6, 2024
First Edition:
September 18, 2024
Citation
Charles Natanson, Willard N. Applefeld, Harvey G. Klein; Hemoglobin-based transfusion strategies for cardiovascular and other diseases: restrictive, liberal, or neither?. Blood 2024; 144 (20): 2075–2082. doi: https://doi.org/10.1182/blood.2024025927
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November 14 2024
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Comments
Trials of transfusion therapy: usual care
In their Perspective of 14 November 2024, Drs. Nathanson, Applefeld, and Klein have expressed their opinion that a "usual-care “control” comparator arm" should be incorporated into the design of randomized clinical trials of transfusion. In their view, in the absence of a usual care arm, trials of transfusion therapy have had and will have unintentional and inadvertent trial design and analysis flaws that result in misinterpretation of data and contribute to erroneous recommendations. Despite the declarative tone of the text, their consideration of countervailing concerns is incomplete. Others have questioned the determination, implementation and interpretation of "usual care" comparators in transfusion trials, given the variability and inconsistency of different practitioners in diverse clinical circumstances as practice patterns evolve over time. "Usual care" arms may have an increased risk of harm to participants. For the past two decades, Dr. Nathanson, with various co-authors, has repeatedly advocated the inclusion of a "usual-care “control” comparator arm" in trials of transfusion therapy. For perspective, during this period, the NIH and other funding sources, the AABB and other stakeholders, peer review panels, Institutional Review Boards, and investigators have decided against inclusion of usual care arms in the design of the landmark trials that have transformed modern transfusion therapy.