Author + information
- Johanne Silvain, MD, PhD∗ (, )http://www.actioncoeur.org,
- Jean-Philippe Collet, MD, PhD and
- Gilles Montalescot, MD, PhD
- ↵∗ACTION Coeur Research Group, Institut de Cardiologie Pitié-Salpêtrière Hospital (APHP), Sorbonne Universités (UPMC), INSERM, UMR_S 1166, Bureau 2-178, 47-83 boulevard de l'Hôpital, 75013 Paris, France
We thank Drs. Giannopoulos and Deftereos for their excellent comments on the potential role of red blood cells (RBCs) as an explanation for the excess of risk due to RBC transfusion.
We share their view on this point as data show an association between cell-free, hemoglobin-based blood substitutes and the risk of myocardial infarction and death (1) that is very similar to the one found in registries between RBC transfusion and poor outcomes in coronary patients. Unfortunately, we lack evidence on the impact of cell-free hemoglobin through endothelial dysfunction and prothrombotic effects in patients receiving a RBC transfusion.
We believe that activation of the P2Y purinergic receptors is one of the relevant mechanisms, as demonstrated in our previous in vitro study (2). Indeed, platelet reactivity was increased using different assays including light transmission aggregometry to adenosine diphosphate (ADP), collagen, and vasodilator-stimulated phosphoprotein phosphorylation platelet reactivity index (VASP-PRI), highly specific tests suggesting a partial activation of the P2Y12 receptors. We concluded that the release of ADP from RBCs might be readily liberated in the context of blood storage, thus representing a potential stimulus for platelet activation and aggregation. The results of the TRANSFUSION-2 study (3) support this hypothesis as the impact on platelet reactivity was found only with tests exploring the P2Y12 receptor pathway and that a correlation between VASP-PRI increase and the duration of RBC storage was found only with this test.
Moreover, it cannot be excluded that there is an even bigger elephant in the room, as even with the best adjusting factors, the real effect of RBC transfusion on the outcomes of coronary patients might be confounded by cessation of life-saving medications. This is likely the case with antithrombotic agents in patients bearing both a high risk of bleeding and experiencing a highly thrombotic situation such as acute coronary syndromes.
At this stage, as suggested in the accompanying editorial of Rao et al. (4), only a well-sized randomized trial with specific data collection (e.g., withdrawal of medication, storage of red blood cells) could answer both important questions of the real clinical impact of red blood cell transfusion in coronary patients and the possible mechanistic explanations for it.
Please note: Prof. Montalescot has received consulting fees from Bayer, Boehringer-Ingelheim, Europa, GlaxoSmithKline, GLG Pharma, Iroko Cardio International, Lead-Up, Luminex, Mc Kinsey, Remedica, Servier, TIMI Group, WebMD, and Wolters; consulting fees and grant support from Bristol-Myers Squibb, AstraZeneca, Biotronik, Eli Lilly, The Medicines Company, Medtronic, Menarini, Sanofi-Aventis, Pfizer, and Accumetrics; and grant support from Abbott Vascular, Daiichi-Sankyo, Nanospheres, and Stentys. Dr. Collet has received research grants from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, Centocor, Fondation de France, INSERM, Fédération Française de Cardiologie, and Société Française de Cardiologie; and consulting and lecture fees from Sanofi-Aventis, Eli Lilly, and Bristol-Myers Squibb. Dr. Silvain has received research grants from Sanofi-Aventis, Daiichi-Sankyo, Eli Lilly, INSERM, Fédération Française de Cardiologie, and Société Française de Cardiologie; consulting fees from Daiichi-Sankyo, and Eli Lilly; and lecture fees from AstraZeneca, Daiichi-Sankyo, and Eli Lilly.
- 2014 American College of Cardiology Foundation
- Silvain J.,
- Abtan J.,
- Kerneis M.,
- et al.
- Rao S.V.,
- Sherwood M.W.