More Evidence That Blood Transfusions Raise Thrombosis Risk in ACS Patients

December 19, 2013

PARIS, FRANCE — Many patients hospitalized with acute coronary syndromes receive blood or blood products due to bleeding complications or in response to anemia, yet there is also evidence that transfusions may be an independent risk factor for ischemic events, observe Dr Johanne Silvain (Hôpital Pitié-Salpêtrière, Paris, France) and colleagues in a study published online December 18, 2013 in the Journal of the American College of Cardiology[1].

In their prospective study exploring mechanisms of platelet function in patients receiving red blood cell (RBC) infusions for anemia, the second Impact of Transfusion of Red Blood Cell on Platelet Activation and Aggregation Studied with Flow Cytometry Use and Light Transmission Aggregometry (TRANSFUSION-2) study, 33 patients had suspected ACS and were on dual antiplatelet therapy with aspirin and a thienopyridine (usually clopidogrel) and 28 had other heart disease and were taking either aspirin or no antiplatelet agent. Their cohort was high risk, they write; one-fifth had diabetes and 41% had renal insufficiency.

In ex vivo testing, platelet reactivity following RBC infusions went up in assays based on ADP interaction with the platelet P2Y12 receptor (thienopyridines are antagonists of that receptor). But they didn't rise as much or at all in several other types of platelet-function tests. The increased platelet reactivity was only "of moderate magnitude" but enough to plausibly account for a potential effect of RBC infusion on ischemic risk, the group speculates.

Indeed, "RBC transfusion must be seen as one additional prothrombotic factor in coronary patients," Prof Gilles Montalescot (Hôpital Pitié-Salpêtrière), the report's senior author, said to heartwire in an email.

The findings also suggest that blood products should probably be used more conservatively in anemic patients without symptoms "when they have had a prior history of coronary artery disease, with or without stenting," according to Montalescot. "Moreover, if a patient has two antiplatelet agents and you want to stop one, you may want to keep the P2Y12 antagonist and remove aspirin, [even though] we usually do the opposite."

In the study, mean maximum platelet aggregation rose 11.6% (p=0.004) and mean residual platelet aggregation rose 10.8% (p=0.005) from baseline to post-RBC infusion using an ADP-induced light-transmission aggregometry assay. The mean vasodilator-stimulated phosphoprotein platelet-reactivity index (VASP PRI) went up 20.7% (p=0.002). There was no significant effect on platelet reactivity in assays based on the arachidonic-acid pathway or collagen provocation. Inflammatory biomarker levels were unaffected, and little effect of RBC storage time on platelet function was seen.

"Conflicting clinical-trial data from studies using different populations, designs, and end points explains the inability of the guidelines to make any recommendation on the role of transfusion in this high-risk patient population," notes an editorial from Drs Sunil V Rao and Matthew W Sherwood (Duke Clinical Research Institute, Durham, NC)[2].

Among the study's limitations, according to Rao and Sherwood, are its observational design (in fact, they note, most data in the field are from observational studies), the possibility of an influence from anemia severity that wasn't picked up, that the effects of transfusion on platelets may be transient, and little information on clinical outcomes.

"To date, there remains equipoise in the field, with no strong evidence for or against red blood cell transfusion in ACS patients," pointing to a need for a definitive randomized trial, they write.

The study was supported by a research grant from the Société Française de Cardiologie/Fédération Française de Cardiologie and by the Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION) group. Silvain discloses receiving research grants from Sanofi, Daiichi-Sankyo, Eli Lilly, INSERM, Fédération Française de Cardiologie, and Société Française de Cardiologie; consultant fees from Daiichi-Sankyo and Eli Lilly; and lecture fees from AstraZeneca, Daiichi-Sankyo, and Eli Lilly. Montalescot discloses receiving research grants or consulting/lecture fees from Abbott Vascular, Asante, AstraZeneca, Atrium, Bayer, Biotronik, Bristol-Myers Squibb, Boehringer-Ingelheim, Boston Scientific, Choice Pharma, Brahms, CCS, CHUV, Cordis, Daiichi-Sankyo, Duke Clinical Research Institute, Eli Lilly, Europa, EuroRSCG, Fédération Française de Cardiologie, Fondation de France, GLG, GlaxoSmithKline, HUG, Indegene, INSERM, Institut de France, Iroko, Lead-up, Medtronic, McKinsey, Merck Sharpe & Dohme, Nanospheres, Navigant, Novartis, Pfizer, Portola, Roche, Royal College of Physicians, Sanofi, Stentys, SGAM, Société Française de Cardiologie, Springer, Thrombosis Research Institute, the Medicines Company, TIMI group, US Zurich, WebMD, and Wolters. Disclosures for the coauthors are listed in the paper. Rao and Sherwood had no conflicts of interest.

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