M Urooj Zafar1, Donald A Smith1, Usman Baber1, Samantha Sartori1, Kevin Chen1, David W Lam1, Carlos A Linares-Koloffon1, Juan Rey-Mendoza1, Gustavo Jimenez Britez1, Gines Escolar1, Valentin Fuster1, Juan J Badimon2. 1. From the Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (M.U.Z., D.A.S., U.B., S.S., K.C., D.W.L., C.A.L.-K., J.R.-M., G.J.B., V.F., J.J.B.); and Department of Hematopathology, Hospital Clinic, Barcelona, Spain (G.E.). 2. From the Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (M.U.Z., D.A.S., U.B., S.S., K.C., D.W.L., C.A.L.-K., J.R.-M., G.J.B., V.F., J.J.B.); and Department of Hematopathology, Hospital Clinic, Barcelona, Spain (G.E.). Juan.Badimon@mssm.edu.
Abstract
BACKGROUND: American College of Cardiology/American Heart Association guidelines advise waiting 5 to 7 days before operating on P2Y12 inhibitor-treated acute coronary syndrome patients, to allow dissipation of its antiplatelet effects. Platelet transfusion is often used to restore hemostasis during operations, but its effectiveness and optimal timing are unclear. We investigated the degree of functional gains obtained from platelet supplementation after loading and maintenance of dual antiplatelet therapy with ticagrelor and the influence of timing on this strategy. METHODS AND RESULTS: After baseline platelet testing (Multiplate Analyzer and VerifyNow), cardiovascular disease patients (n=20; 56.9±7.9 years; 65% men; 75% diabetic) received dual antiplatelet therapy as a single loading dose (ticagrelor 180 mg plus aspirin 325 mg) and as daily/maintenance treatment for 5 to 7 days (maintenance therapy: ticagrelor 90 mg BID plus aspirin 81 mg QD). At 4, 6, 24, and 48 hours from (last) dosing, patients' blood samples were supplemented with concentrated platelets from healthy donors in vitro, raising platelet counts by 0% (unsupplemented control), 25%, 50%, and 75%, and the function retested. Reactivity in supplemented samples was compared with respective 0% sample and with the pretreatment baseline. Results under loading dose and maintenance therapy regimens were nearly identical. Platelet reactivity was higher (P<0.05) in nearly all supplemented samples versus respective controls. Aggregations with supplementation were 59% to 79% of baseline at 24 hours and equal to baseline at 48 hours. CONCLUSIONS: Platelet reactivity of ticagrelor-treated patients can be restored using concentrated platelets after a loading dose/maintenance therapy in a time-dependent manner under in vitro testing. Although statistically significant improvements are evident 6 hours after (last) dosing, ≥24 hours maybe needed for clinically meaningful restoration in platelet function. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02201394.
BACKGROUND: American College of Cardiology/American Heart Association guidelines advise waiting 5 to 7 days before operating on P2Y12 inhibitor-treated acute coronary syndromepatients, to allow dissipation of its antiplatelet effects. Platelet transfusion is often used to restore hemostasis during operations, but its effectiveness and optimal timing are unclear. We investigated the degree of functional gains obtained from platelet supplementation after loading and maintenance of dual antiplatelet therapy with ticagrelor and the influence of timing on this strategy. METHODS AND RESULTS: After baseline platelet testing (Multiplate Analyzer and VerifyNow), cardiovascular diseasepatients (n=20; 56.9±7.9 years; 65% men; 75% diabetic) received dual antiplatelet therapy as a single loading dose (ticagrelor 180 mg plus aspirin 325 mg) and as daily/maintenance treatment for 5 to 7 days (maintenance therapy: ticagrelor 90 mg BID plus aspirin 81 mg QD). At 4, 6, 24, and 48 hours from (last) dosing, patients' blood samples were supplemented with concentrated platelets from healthy donors in vitro, raising platelet counts by 0% (unsupplemented control), 25%, 50%, and 75%, and the function retested. Reactivity in supplemented samples was compared with respective 0% sample and with the pretreatment baseline. Results under loading dose and maintenance therapy regimens were nearly identical. Platelet reactivity was higher (P<0.05) in nearly all supplemented samples versus respective controls. Aggregations with supplementation were 59% to 79% of baseline at 24 hours and equal to baseline at 48 hours. CONCLUSIONS: Platelet reactivity of ticagrelor-treated patients can be restored using concentrated platelets after a loading dose/maintenance therapy in a time-dependent manner under in vitro testing. Although statistically significant improvements are evident 6 hours after (last) dosing, ≥24 hours maybe needed for clinically meaningful restoration in platelet function. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02201394.
Authors: Minka J A Vries; Heleen J Bouman; Renske H Olie; Leo F Veenstra; Suzanne Zwaveling; Paul W M Verhezen; Arina J Ten Cate-Hoek; Hugo Ten Cate; Yvonne M C Henskens; Paola E J van der Meijden Journal: Eur Heart J Cardiovasc Pharmacother Date: 2016-09-07
Authors: P Gabriel Steg; Robert A Harrington; Håkan Emanuelsson; Hugo A Katus; Kenneth W Mahaffey; Bernhard Meier; Robert F Storey; Daniel M Wojdyla; Basil S Lewis; Gerald Maurer; Lars Wallentin; Stefan K James Journal: Circulation Date: 2013-07-30 Impact factor: 29.690
Authors: Udaya S Tantry; Laurent Bonello; Daniel Aradi; Matthew J Price; Young-Hoon Jeong; Dominick J Angiolillo; Gregg W Stone; Nick Curzen; Tobias Geisler; Jurrien Ten Berg; Ajay Kirtane; Jolanta Siller-Matula; Elisabeth Mahla; Richard C Becker; Deepak L Bhatt; Ron Waksman; Sunil V Rao; Dimitrios Alexopoulos; Rossella Marcucci; Jean-Luc Reny; Dietmar Trenk; Dirk Sibbing; Paul A Gurbel Journal: J Am Coll Cardiol Date: 2013-09-27 Impact factor: 24.094
Authors: Philippe Gabriel Steg; Stefan James; Robert A Harrington; Diego Ardissino; Richard C Becker; Christopher P Cannon; Håkan Emanuelsson; Ariel Finkelstein; Steen Husted; Hugo Katus; Jan Kilhamn; Sylvia Olofsson; Robert F Storey; W Douglas Weaver; Lars Wallentin Journal: Circulation Date: 2010-11-08 Impact factor: 29.690
Authors: M U Zafar; C Santos-Gallego; D A Vorchheimer; J F Viles-Gonzalez; S Elmariah; C Giannarelli; S Sartori; D S Small; J A Jakubowski; V Fuster; J J Badimon Journal: J Thromb Haemost Date: 2013-01 Impact factor: 5.824
Authors: Kambiz Hassan; Tabea Brüning; Michael Caspary; Peter Wohlmuth; Holger Pioch; Michael Schmoeckel; Stephan Geidel Journal: Ann Thorac Cardiovasc Surg Date: 2022-01-20 Impact factor: 1.889