TRANSFUSION-2: Red blood cell transfusion prompts increase in platelet reactivity

An increase in platelet reactivity was observed after red blood cell transfusion, which could explain post-transfusion spikes in ischemic events and mortality in patients with ACS, according to new study findings.

The increase was especially noticeable with tests measuring the adenosine diphosphate-P2Y₁₂ pathway without much variation in inflammatory or thrombotic biomarkers, Johanne Silvain, MD, PhD, of Université Pierre et Marie Curie, Paris, and colleagues found. An exploratory subgroup analysis indicated that patients with ACS treated with P2Y12 inhibitors had a higher increase in platelet reactivity compared with patients without ACS who were not taking P2Y12 inhibitors.

“This in vivo effect may account for the excess in ischemic events observed in the context of ACS treated by PCI and P2Y12 inhibitors,” the researchers wrote.

Silvain and colleagues measured platelet reactivity before and after red blood cell transfusion in 61 patients (28 with ACS). Patients with ACS were treated with a P2Y12 inhibitor (clopidogrel, 28; prasugrel [Effient, Daiichi Sankyo/Eli Lilly], 5) and aspirin. Patients without ACS were hospitalized for another cardiac disease and were treated with aspirin only or no antiplatelet agent. The researchers also measured inflammatory and thrombotic biomarkers and changes in maximum and residual platelet aggregation before and after transfusion.

Platelet reactivity rose after transfusion

Platelet reactivity was increased after red blood cell transfusion when measured either by Vasodilator-Stimulated Phosphoprotein Platelet Reactivity Index (relative increase, 20.7%; P=.002) or by adenosine diphosphate-induced light transmission aggregometry (relative increase of maximum platelet aggregation, 11.6%; P=.004; increase of residual platelet aggregation, 10.8%; P=.005). While there was a trend towards an increase of P-selectin expression, it was not significant.

The analysis yielded similar results with the nonspecific agonist thombin receptor activated peptide (relative increase of maximum platelet aggregation, 11.7%; P=.04; increase of residual platelet aggregation, 12.7%; P=.02), but not with collagen or arachidonic acid agonists. There was also found little variation in inflammatory or thrombotic biomarkers.

In an exploratory subgroup analysis using measurement by with light transmission aggregometry, the researchers found that patients with ACS treated with P2Y12 inhibitors had a greater increase in platelet reactivity after transfusion (relative increase of maximum platelet aggregation, 20.4%; P=.002; relative increase of residual platelet aggregation, 15.6%; P=.03) compared with patients without ACS not treated with P2Y12 inhibitors (relative increase of maximum platelet aggregation, 4.7%; P=.2; relative increase of residual platelet aggregation, 0.7%; P=.4).

“The hypothesis that can be made is that [red blood cell] transfusion could directly impact platelet reactivity through activation of the P2Y12 platelet receptor or within the [adenosine diphosphate] pathway by agonist or mediators contained in [red blood cell] packs,” the researchers wrote.

They suggested that “the risk/benefit of transfusion should be weighed on an individual basis in ACS patients until a randomized controlled trial on conservative vs. liberal treatment of anemic ACS patients clarifies this issue.”

Sunil V. Rao

Randomized trial needed

In a related editorial, Sunil V. Rao, MD, and Matthew W. Sherwood, MD, both of Duke Clinical Research Institute, said these findings offer some useful mechanistic explanations, but there remains an “urgent need for a definitive randomized trial of transfusion strategies in patients with ACS.”

While as many as 10% of patients with ACS receive a blood transfusion during their hospital stay, “given the lack of data in this population, it is impossible to know how many of these transfusions are inappropriate,” they wrote.

For more information:

Rao SV. J Am Coll Cardiol. 2013;doi:10.1016/j.jacc.2013.11.028.

Silvain J. J Am Coll Cardiol. 2013;doi:10.1016/j.jacc.2013.11.029.

Disclosure: See the full study for a list of the researchers’ relevant financial disclosures. Rao and Sherwood report no relevant financial disclosures.