Stephen A O'Connor1, Julien Amour1, Anne Mercadier1, Réjane Martin1, Mathieu Kerneis1, Jérémie Abtan1, Delphine Brugier1, Johanne Silvain1, Olivier Barthélémy1, Pascal Leprince1, Gilles Montalescot2, Jean-Philippe Collet1. 1. From the Sorbonne Université UMPC (Paris 6), INSERM_UMRS1166 (S.A.O., R.M., M.K., J.A., D.B., J.S., O.B., P.L., G.M., J.-P.C.), ACTION Study Group, Paris, France (S.A.O., R.M., M.K., J.A., D.B., J.S., O.B., G.M., J.-P.C.), Département d'Anesthésie et de Réanimation (J.A., R.M.), Etablissement Français Sang (A.M.), and Institut de Cardiologie and Chirurgie Cardiaque (S.A.O., M.K., J.A., D.B., J.S., O.B., P.L., G.M., J.-P.C.), Pitié-Salpêtrière Hospital (AP-HP), Paris, France. 2. From the Sorbonne Université UMPC (Paris 6), INSERM_UMRS1166 (S.A.O., R.M., M.K., J.A., D.B., J.S., O.B., P.L., G.M., J.-P.C.), ACTION Study Group, Paris, France (S.A.O., R.M., M.K., J.A., D.B., J.S., O.B., G.M., J.-P.C.), Département d'Anesthésie et de Réanimation (J.A., R.M.), Etablissement Français Sang (A.M.), and Institut de Cardiologie and Chirurgie Cardiaque (S.A.O., M.K., J.A., D.B., J.S., O.B., P.L., G.M., J.-P.C.), Pitié-Salpêtrière Hospital (AP-HP), Paris, France. gilles.montalescot@psl.aphp.fr.
Abstract
BACKGROUND: Allogenic platelet transfusions (PT) are administered to treat excessive bleeding in patients on P2Y12 receptor inhibitors (RI). We assessed the effect of ex vivo and in vivo PT on platelet activation and aggregation in patients on dual antiplatelet therapy. METHODS AND RESULTS: In the Antagonize P2Y12 Treatment Inhibitors by Transfusion of Platelets in an Urgent or Delayed Timing After Acute Coronary Syndrome or Percutaneous Coronary Intervention Presentation-Acute Coronary Syndrome (APTITUDE-ACS) study, patients presenting with acute coronary syndrome or for elective percutaneous coronary intervention, receiving loading doses of clopidogrel (600 mg, n=13 or 900 mg, n=12), prasugrel 60 mg (n=10), or ticagrelor 180 mg (n=10) were included. PT was performed ex vivo by mixing platelet-rich plasma from blood sampling performed at baseline in increasing proportions with platelet-rich plasma sampled 4 hours after loading dose. The percentage restoration of residual platelet aggregation achieved with 80% proportion PT (residual platelet aggregation 80% PT mix/residual platelet aggregation baseline×100) significantly decreased with increasing potency of P2Y12 RI (83.9±11%, 73±14%, 66.3±15%, 40.9±19% for clopidogrel 600 mg, clopidogrel 900 mg, prasugrel, and ticagrelor, respectively; P for trend <0.0001). In the APTITUDE-Coronary Artery Bypass Graft (APTITUDE-CABG) study, vasodilator-stimulated phosphoprotein-platelet reactivity index, a specific marker of the P2Y12 RI drug-effect, was assessed before and after in vivo PT administered for excessive bleeding in patients undergoing cardiac surgery while on a maintenance dose of aspirin and clopidogrel (n=45), prasugrel (n=6), or ticagrelor (n=3). When compared with baseline, there was a significant relative increase of 23.1% in platelet activation after PT transfusion (42.2±23.6% versus 56.6±18.2%; P=0.0008). CONCLUSIONS: PT restores platelet reactivity in patients with acute coronary syndrome/percutaneous coronary intervention and in patients undergoing cardiac surgery on P2Y12 RI while bleeding with a less effect with increasing potency of P2Y12 inhibition. CLINICAL TRIAL REGISTRATION: URL: http://www.recherche-biomedicale.sante.gouv.fr/pro/comites/coordonnees.htm and http://www.cnil.fr/. Unique identifiers: No. 301111 and No. 1547216v0.
BACKGROUND: Allogenic platelet transfusions (PT) are administered to treat excessive bleeding in patients on P2Y12 receptor inhibitors (RI). We assessed the effect of ex vivo and in vivo PT on platelet activation and aggregation in patients on dual antiplatelet therapy. METHODS AND RESULTS: In the Antagonize P2Y12 Treatment Inhibitors by Transfusion of Platelets in an Urgent or Delayed Timing After Acute Coronary Syndrome or Percutaneous Coronary Intervention Presentation-Acute Coronary Syndrome (APTITUDE-ACS) study, patients presenting with acute coronary syndrome or for elective percutaneous coronary intervention, receiving loading doses of clopidogrel (600 mg, n=13 or 900 mg, n=12), prasugrel 60 mg (n=10), or ticagrelor 180 mg (n=10) were included. PT was performed ex vivo by mixing platelet-rich plasma from blood sampling performed at baseline in increasing proportions with platelet-rich plasma sampled 4 hours after loading dose. The percentage restoration of residual platelet aggregation achieved with 80% proportion PT (residual platelet aggregation 80% PT mix/residual platelet aggregation baseline×100) significantly decreased with increasing potency of P2Y12 RI (83.9±11%, 73±14%, 66.3±15%, 40.9±19% for clopidogrel 600 mg, clopidogrel 900 mg, prasugrel, and ticagrelor, respectively; P for trend <0.0001). In the APTITUDE-Coronary Artery Bypass Graft (APTITUDE-CABG) study, vasodilator-stimulated phosphoprotein-platelet reactivity index, a specific marker of the P2Y12 RI drug-effect, was assessed before and after in vivo PT administered for excessive bleeding in patients undergoing cardiac surgery while on a maintenance dose of aspirin and clopidogrel (n=45), prasugrel (n=6), or ticagrelor (n=3). When compared with baseline, there was a significant relative increase of 23.1% in platelet activation after PT transfusion (42.2±23.6% versus 56.6±18.2%; P=0.0008). CONCLUSIONS: PT restores platelet reactivity in patients with acute coronary syndrome/percutaneous coronary intervention and in patients undergoing cardiac surgery on P2Y12 RI while bleeding with a less effect with increasing potency of P2Y12 inhibition. CLINICAL TRIAL REGISTRATION: URL: http://www.recherche-biomedicale.sante.gouv.fr/pro/comites/coordonnees.htm and http://www.cnil.fr/. Unique identifiers: No. 301111 and No. 1547216v0.
Authors: Lisa Schoener; Stefanie Jellinghaus; Bernhardt Richter; Christian Pfluecke; Georg Ende; Marian Christoph; Silvio Quick; Tobias Loehn; Uwe Speiser; David M Poitz; Johannes Mierke; Ruth H Strasser; Karim Ibrahim Journal: Clin Res Cardiol Date: 2017-06-26 Impact factor: 5.460
Authors: M Urooj Zafar; Donald A Smith; Usman Baber; Samantha Sartori; Kevin Chen; David W Lam; Carlos A Linares-Koloffon; Juan Rey-Mendoza; Gustavo Jimenez Britez; Gines Escolar; Valentin Fuster; Juan J Badimon Journal: Circ Cardiovasc Interv Date: 2017-08 Impact factor: 6.546