Literature DB >> 28653184

Reversal of the platelet inhibitory effect of the P2Y12 inhibitors clopidogrel, prasugrel, and ticagrelor in vitro: a new approach to an old issue.

Lisa Schoener1, Stefanie Jellinghaus2, Bernhardt Richter2, Christian Pfluecke2, Georg Ende2, Marian Christoph2, Silvio Quick2, Tobias Loehn2, Uwe Speiser2, David M Poitz2, Johannes Mierke2, Ruth H Strasser2, Karim Ibrahim2.   

Abstract

AIM: Platelet transfusion is an effective option to reverse platelet inhibition in thienopyridine-treated patients suffering from bleedings or requiring urgent surgery. However, in ticagrelor-treated patients, the previous studies revealed significant clinical effects to platelet rich plasma (PRP) but poor response to pooled platelets (PP) as used in clinical routine. The aim of this study was to elucidate a potential pathomechanism to explain the poor response of ticagrelor to PP. METHODS AND
RESULTS: From 79 whole blood samples of patients treated with ticagrelor, prasugrel, or clopidogrel, the PRI-VASP was determined before and after in vitro platelet supplementation of PP or PRP at increasing concentrations. Compared to prasugrel- and clopidogrel-treated patients, the PRI-VASP of ticagrelor-treated patients showed no significant increase after in vitro administration of PP. PRI-VASP was performed in ticagrelor-treated samples after in vitro addition of 1: centrifuged PRP platelets resuspended in PP buffer, 2: PP with human serum, 3: human serum alone. Surprisingly, PP with human serum or human serum alone were able to significantly increase PRI-VASP in samples of ticagrelor-treated patients (11.7 ± 10.9 → 61.3 ± 10.9%, p = 0.006; 11.7 ± 10.9 → 54.1 ± 2.7%, p < 0.001). This effect could also be shown using human albumin (18.9 ± 5.1% → 80 g/l human albumin: 48.1 ± 8.3%, p < 0.001).
CONCLUSION: The present study demonstrates that addition of human serum and human albumin alone is able to reverse the ticagrelor effects in vitro and supports our novel hypothesis of the importance of proteins in reversing the effects of ticagrelor by binding active ticagrelor.

Entities:  

Keywords:  Antiplatelet therapy; Bleeding complications; Reversal; Ticagrelor

Mesh:

Substances:

Year:  2017        PMID: 28653184     DOI: 10.1007/s00392-017-1128-8

Source DB:  PubMed          Journal:  Clin Res Cardiol        ISSN: 1861-0684            Impact factor:   5.460


  21 in total

Review 1.  Ticagrelor: a novel reversible oral antiplatelet agent.

Authors:  James J Nawarskas; Sara M Clark
Journal:  Cardiol Rev       Date:  2011 Mar-Apr       Impact factor: 2.644

2.  Prolonged dual antiplatelet therapy after drug-eluting stenting: meta-analysis of randomized trials.

Authors:  Salvatore Cassese; Robert A Byrne; Gjin Ndrepepa; Heribert Schunkert; Massimiliano Fusaro; Adnan Kastrati
Journal:  Clin Res Cardiol       Date:  2015-04-23       Impact factor: 5.460

3.  Clinical outcomes of dual antiplatelet therapy after implantation of drug-eluting stents in patients with different cardiovascular risk factors.

Authors:  Seung-Yul Lee; Myeong-Ki Hong; Dong-Ho Shin; Jung-Sun Kim; Byeong-Keuk Kim; Young-Guk Ko; Donghoon Choi; Yangsoo Jang; Hyo-Soo Kim; Marco Valgimigli; Tullio Palmerini; Gregg W Stone
Journal:  Clin Res Cardiol       Date:  2016-09-08       Impact factor: 5.460

4.  Low platelet reactivity is recovered by transfusion of stored platelets: a healthy volunteer in vivo study.

Authors:  F Prüller; C Drexler; S Archan; S Macher; R B Raggam; E Mahla
Journal:  J Thromb Haemost       Date:  2011-08       Impact factor: 5.824

5.  Reversal strategy in antagonizing the P2Y12 -inhibitor ticagrelor.

Authors:  Eva-Luise Hobl; Ulla Derhaschnig; Christa Firbas; Christian Schoergenhofer; Michael Schwameis; Bernd Jilma
Journal:  Eur J Clin Invest       Date:  2013-09-23       Impact factor: 4.686

6.  Normalization of platelet reactivity in clopidogrel-treated subjects.

Authors:  G Vilahur; B G Choi; M U Zafar; J F Viles-Gonzalez; D A Vorchheimer; V Fuster; J J Badimon
Journal:  J Thromb Haemost       Date:  2007-01       Impact factor: 5.824

7.  Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin.

Authors:  Steen Husted; Håkan Emanuelsson; Stan Heptinstall; Per Morten Sandset; Mark Wickens; Gary Peters
Journal:  Eur Heart J       Date:  2006-02-13       Impact factor: 29.983

8.  Effects of ex vivo platelet supplementation on platelet aggregability in blood samples from patients treated with acetylsalicylic acid, clopidogrel, or ticagrelor.

Authors:  E C Hansson; C Shams Hakimi; K Åström-Olsson; C Hesse; H Wallén; M Dellborg; P Albertsson; A Jeppsson
Journal:  Br J Anaesth       Date:  2013-10-22       Impact factor: 9.166

9.  Platelet function normalization after a prasugrel loading-dose: time-dependent effect of platelet supplementation.

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

10.  Efficacy of ex vivo autologous and in vivo platelet transfusion in the reversal of P2Y12 inhibition by clopidogrel, prasugrel, and ticagrelor: the APTITUDE study.

Authors:  Stephen A O'Connor; Julien Amour; Anne Mercadier; Réjane Martin; Mathieu Kerneis; Jérémie Abtan; Delphine Brugier; Johanne Silvain; Olivier Barthélémy; Pascal Leprince; Gilles Montalescot; Jean-Philippe Collet
Journal:  Circ Cardiovasc Interv       Date:  2015-11       Impact factor: 6.546

View more
  5 in total

Review 1.  Antithrombotic therapy in patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention: should we change our practice after the PIONEER AF-PCI and RE-DUAL PCI trials?

Authors:  D Duerschmied; J Brachmann; H Darius; N Frey; H A Katus; W Rottbauer; A Schäfer; H Thiele; C Bode; Uwe Zeymer
Journal:  Clin Res Cardiol       Date:  2018-04-20       Impact factor: 5.460

Review 2.  Targeting ticagrelor: a novel therapy for emergency reversal.

Authors:  Brandon Cave; Aranyak Rawal; Devarshi Ardeshna; Uzoma N Ibebuogu; Chittoor B Sai-Sudhakar; Rami N Khouzam
Journal:  Ann Transl Med       Date:  2019-09

3.  Austrian recommendations for best clinical practice in case of haemorrhagic traumatic brain injury under platelet inhibitors or non-vitamin K antagonist oral anticoagulants: an additional therapeutic option to consider.

Authors:  Patrick M Honore; Aude Mugisha; Luc Kugener; Sebastien Redant; Rachid Attou; Andrea Gallerani; David De Bels
Journal:  Crit Care       Date:  2020-05-08       Impact factor: 9.097

4.  Associations of PER3 polymorphisms with clopidogrel resistance among Chinese Han people treated with clopidogrel.

Authors:  Nan Zheng; Fengying Yin; Qinglin Yu; Jinyan Zhong; Jin Yang; Zhifeng Xu; Jia Su; Xiaomin Chen
Journal:  J Clin Lab Anal       Date:  2021-01-26       Impact factor: 2.352

5.  Synthesis of a Novel Series of Amino Acid Prodrugs Based on Thienopyridine Scaffolds and Evaluation of Their Antiplatelet Activity.

Authors:  Nan Lu; Lingjun Li; Xuemin Zheng; Shijun Zhang; Yuquan Li; Jing Yuan; Qunchao Wei; Youjun Xu; Fancui Meng
Journal:  Molecules       Date:  2018-04-28       Impact factor: 4.411

  5 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.