When should you transfuse?

A common practice among nephrologists is to aim for a Hb concentration above 10 g/dL. Indeed, one of the arguments for targeting a Hb above 10 g/dL is the perceived risk that it might increase the likelihood of a blood transfusion. In the 2007 NKF K-DOQI Anemia Guideline (the article is not available open access), there are the following statements:

2.1.1 In the opinion of the Work Group, selection of the Hb target and selection of the Hb level at which ESA therapy is initiated in the individual patient should include consideration of potential benefits (including improvement in quality of life and avoidance of transfusion) and potential harms (including the risk of life-threatening adverse events). (Clinical Practice RECOMMENDATION)

2.1.2 In the opinion of the Work Group, in dialysis and nondialysis patients with CKD receiving ESA therapy, the selected Hb target should generally be in the range of 11.0 to 12.0 g/dl. (Clinical Practice RECOMMENDATION)

2.1.3 In dialysis and nondialysis patients with CKD receiving ESA therapy, the Hb target should not be greater than 13.0 g/dl. (Clinical Practice GUIDELINE - MODERATELY STRONG EVIDENCE)

In June 2011 the US FDA modified the ESA label and recommended that the ESA dose should be reduced or interrupted to maintain the Hb concentration <11 g/dL; in Europe, the common practice seems to be a Hb target of 10-12 g/dL. However, even now the FDA states: “Therapy should be individualized to the patient and the lowest possible ESA dose given to reduce the need for transfusions.”

My own practice is to approach anemia management is by identifying the individualized Hb trigger for the patient. The Hb trigger is defined as the Hb concentration at which an intervention is required – be it initiation or increase in ESA dose, a blood transfuion, or iron treatment. This approach has been opposed by industry: ostensibly on the grounds that this would increase the rate of blood transfusion, but I think we all see through this and recognize that it's because there would be less profits for industry.

This brings me to the guideline published by Jeffrey Carson and colleagues in the current issue of the Annals of Internal Medicine  [It is available open access]. They state: “The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children.”

The guideline is a “must read”. Well written and balanced. A committee of 20 experts contributed. Unlike some of the nephrology guidelines, the AABB was careful to exclude experts with conflict of interest. They state: “Committee members had no substantial conflicts of interest as defined by the AABB conflict of interest policy”. And, importantly, unlike some of the nephrology guidelines, support for the development of this guideline was provided by the AABBrather than one or more commercial concerns. They also used an evidence-based process that employed the GRADE method.

Recommendation 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence).

Recommendation 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence).

Recommendation 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence).

Recommendation 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).

The bottom-line: The AABB guidelines are clear: even for hospitalized patients with pre-existing cardiovascular disease – and many of our CKD stage 4 and 5 and 5D patients fall within this spectrum – transfusion should be considered if the Hb level is <8 g/dL. In hospitalized stable patients, strong high-quality evidence supports a recommendation of transfusing if the Hb concentration is 7-8 g/dL.

In my view, the idea that patient's should be routinely transfused when their Hb falls below 10 g/dL should be abandoned. Rather, after establishing the Hb trigger for the patient - somewhere between 8 to 10 g/dL for most patients - one should increase the ESA dose and if indicated administer iron. For those patients with a low Hb concentration, in whom blood transfusion is not contraindicated, (for example, a transfusion should be avoided in potential transplant recipients), and who are non-responsive to ESA, a blood transfusion is a reasonable next step. 

Therefore, to answer the question: when to transfuse CKD patients? The answer should be: usually not until the Hb goes below 8 g/dL. And then transfuse after carefully considering the pros and cons and then only after individualizing the decision.