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

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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.

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Author notes

  1. Lisa Schoener and Stefanie Jellinghaus contributed equally to this manuscript.

Authors and Affiliations

  1. Technische Universität Dresden, Heart Center Dresden, University Hospital Dresden, Fetscherstraße 76, 01307, Dresden, Germany

    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

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  1. Lisa Schoener
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  2. Stefanie Jellinghaus
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  3. Bernhardt Richter
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  5. Georg Ende
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  6. Marian Christoph
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Correspondence to Lisa Schoener.

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Conflict of interest

Dr. Ibrahim and Prof. Strasser report grants from AstraZeneca and grants from Daiichi sankyo outside the submitted work.

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Schoener, L., Jellinghaus, S., Richter, B. et al. Reversal of the platelet inhibitory effect of the P2Y12 inhibitors clopidogrel, prasugrel, and ticagrelor in vitro: a new approach to an old issue. Clin Res Cardiol 106, 868–874 (2017). https://doi.org/10.1007/s00392-017-1128-8

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  • DOI: https://doi.org/10.1007/s00392-017-1128-8

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