More restrictive hemoglobin threshold recommended for transfusion

Mark H. Yazer, MD; Darrell J. Triulzi, MD

18 October 2016

New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.

The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.

The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.

The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.

This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).

“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.

Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.

However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.

They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.

The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.

While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.

“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.

Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.

The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.

They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.

Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.


Guidelines support individualized transfusion decisions

The two-tiered approach of this important update to the red blood cell transfusion guidelines acknowledges the current state of the evidence and also provides support for making more individualized transfusion decisions.

These new guidelines represent medicine at its best in that they are evidence based, derived from randomized controlled trials, reflect important clinical perspectives, and are definitive for conditions in which data are substantial, but provide greater flexibility for conditions in which data are less certain.

One major limitation of these guidelines is that they are based on hemoglobin level as the transfusion trigger, when good clinical practice dictates that the decision to transfuse should also be based on clinical factors, availability of alternative therapies, and patient preferences.

Source: adapted from an editorial (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.10887)


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