Restrictive Transfusion Strategy May Lower Infection Risk

Larry Hand

April 01, 2014

Restricting red blood cell (RBC) transfusions to hospital patients whose hemoglobin levels fall below 7 g/dL may significantly decrease the risk for healthcare-acquired infections (HAIs), according to an article published in the April 2 issue of JAMA.

Jeffrey M. Rohde, MD, from the Department of Internal Medicine, University of Michigan, Ann Arbor, and colleagues conducted a systematic review and meta-analysis of published clinical trials to compare restrictive vs liberal transfusion strategies and the risk for HAI. They also assessed whether HAI risk is independently associated with removal of white blood cells before transfusions.

The investigators identified 21 randomized trials involving 8735 patients who had had transfusions. Of those, 18 trials with 7593 patients met prespecified criteria and were included in the final analysis.

The summary risk for all serious infections was 11.8% (95% CI, 7.0% - 16.7%) for restrictive transfusion strategies compared with 16.9% (95% CI, 8.9% - 25.4%) for liberal strategies. The overall pooled risk ratio (RR) for HAIs with restrictive vs liberal thresholds was 0.88 (95% confidence interval [CI], 0.78 - 0.99; P = .033), with the restrictive hemoglobin threshold ranging from 6.4 to 9.7 g/dL and the liberal threshold ranging from 9.0 to 11.3 g/dL.

The researchers estimate a restrictive strategy would reduce the number of infections by 26.5 per 1000 patients (95% CI, 8.2 - 42.5).

Eight of the 18 trials covered exclusively leukocyte-reduced transfusions, and the reduction in risk for infection with restrictive transfusion strategies remained (RR, 0.80; 95% CI, 0.67 - 0.95; P = .011).

When the investigators stratified patients by type of ailment, the association for reduced risk with restrictive policies remained for patients with hip or knee replacements (RR, 0.70; 95% CI, 0.54 - 0.91; P = .007) and those with sepsis (RR, 0.51; 95%CI, 0.28 - 0.95). The association was not significant, however, for cardiac or critically ill patients or among patients who had acute upper gastrointestinal bleeding.

Four randomized trials used hemoglobin thresholds of less than 7 g/dL, and the pooled RR for them was 0.82 (95% CI, 0.70 - 0.97; P = .023). For these trials, the researchers calculated that for the restrictive strategy, 1 of 20 patients could avoid an HAI, and that the number of avoided HAIs per 1000 patients was 48.9 (95% CI, 7.5 - 83.6).

Common Inpatient Procedure

About 14 million RBC units were transfused in 2011 in the United States, 84.8% of which had white blood cells removed as a precaution against possible immune system compromises.

"Leukocyte reduction of RBCs has been shown to decrease the risk of health care-associated infection, and because only 85% of RBC units are leukocyte-reduced in the United States, adoption of universal leukocyte reduction may be an important first step to infection prevention," the researchers write. "However, even with leukocyte-reduced RBC units, adherence to a restrictive transfusion strategy is an important second step in preventing health care-associated infections."

However, in an accompanying editorial, Jeffrey L. Carson, MD, from the Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, notes that the only outcome in the study was infection risk and that "mortality, myocardial infarction, and function should be considered in the overall risk-benefit analysis of transfusion."

He adds that most studies have compared hemoglobin thresholds of 7 or 8 g/dL with 10 g/dL, which reflect clinical practice. "It is likely that transfusion is life-saving, but not across the entire range of hemoglobin thresholds currently used to trigger a transfusion," he writes.

"The study by Rohde et al confirms another potential adverse outcome associated with transfusion: serious infectious disease," he concludes. "Clinical trials are needed to establish the optimal transfusion thresholds, to provide additional information about the risks and benefits of RBC transfusion, and to determine how best to use RBC transfusion."

This research was funded by the National Heart, Lung, and Blood Institute. One coauthor has reported giving expert testimony on legal cases focusing on medical malpractice; receiving payment from the National Institutes of Health, Veterans Affairs, and the Blue Cross Blue Shield of Michigan Foundation to his institution; receiving payment for lectures from many academic meetings, group-purchasing organizations, state hospital associations, and nonprofit organizations; receiving royalties for edited or authored books from Lippincott Williams &Wilkins, McGraw-Hill, and Wiley-Blackwell; and serving on the board for Doximity and Jvion. The other authors have disclosed no relevant financial relationships. Dr Carson has reported serving as a consultant to Cerus for a trial unrelated to this article and reports receiving grant funding to his institution from the National Institutes of Health.

JAMA. 2014;311:1293-1294, 1317-1326.


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