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Ticagrelor reversal: in vitro assessment of four haemostatic agents
  1. Leyla Calmette1,2,3,
  2. Anne-Céline Martin1,2,4,
  3. Bernard Le Bonniec1,2,
  4. Diane Zlotnik1,2,
  5. Isabelle Gouin-Thibault1,2,3,
  6. Christilla Bachelot-Loza1,2,
  7. Pascale Gaussem1,2,5,
  8. Anne Godier1,2,6
  1. 1 Faculté de Pharmacie, Inserm UMR-S1140, Paris, France
  2. 2 Université Paris Descartes, Sorbonne Paris Cité, Paris, France
  3. 3 Laboratoire d'Hématologie, AP-HP, Hôpital Cochin, Paris, France
  4. 4 Service de Cardiologie, Hôpital Val de Grâce, Paris, France
  5. 5 Service d'Hématologie Biologique, AP-HP, Hôpital Européen Georges Pompidou, Paris, France
  6. 6 Service d'Anesthésie-Réanimation, Fondation Rothschild, Paris, France
  1. Correspondence to Dr Anne Godier, Department of Anaesthesia and Critical Care, Fondation Rothschild, 25 rue Manin, Paris 75019, France; agodier{at}fo-rothschild.fr

Abstract

Aim Management of ticagrelor-induced bleeding is challenging as platelet transfusion is ineffective. An effective strategy is needed. This study aimed to investigate in vitro the efficacy of four haemostatic drugs (HDs), namely recombinant activated factor VII (rFVIIa), fibrinogen concentrate (Fib), tranexamic acid (TXA) and factor XIII concentrate (FXIII) to improve the haemostatic capacity in the presence of ticagrelor.

Methods Blood was spiked with ticagrelor then supplemented by either HD or control. Several assays were performed: ADP-induced platelet aggregation measured by impedance aggregometry, light transmission and two global assays, thrombolastography with the platelet mapping device (TEG-PM) and a platelet-dependent thrombin generation assay (TGA).

Results Ticagrelor inhibited ADP-induced platelet aggregation and decreased the clot strength maximum amplitude (MA) in TEG-PMADP. None of the HDs corrected these parameters. However, rFVIIa shortened the coagulation time R using TEG-PMthrombin and the time to peak prolonged by ticagrelor in TGA. Fib increased MAthrombin and FXIII decreased LY30. TXA had no effects.

Conclusions Whereas none of the HDs corrected ticagrelor-induced platelet inhibition, rFVIIa shortened coagulation times, Fib increased clot firmness and FXIII decreased fibrinolysis. Consequently, they may bypass ticagrelor effects by acting on fibrin formation or fibrinolysis. Further studies are needed to confirm these data in vivo.

  • BLEEDING DISORDERS
  • PLASMA VISCOSITY
  • HAEMOSTASIS
  • ANTICOAGULANTS

https://doi.org/10.1136/jclinpath-2016-204117

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    Footnotes

    • This work was carried out at Inserm UMR-S1140, Paris, France

    • Handling editor Mary Frances McMullin

    • Contributors LC and A-CM participated in the design of the study, performed whole blood experiments, analysed the results, prepared the figures and wrote the manuscript. BLB, DZ and IG-T participated in data analysis and provided critical revisions to the manuscript. CB-L, PG and AG conceived the study, analysed the results and provided critical revisions to the manuscript. The final version was approved by all authors.

    • Funding Ticagrelor was kindly provided by AstraZeneca (Mölndal, Sweden), factor XIII concentrate by CSL Behring (Paris, France), and TEG devices and TEG reagents by Haemonetics Corporation (Braintree, Massachusetts, USA). The study was otherwise funded by institutional sources, by grants from CSL Behring and the Conny Maeva Charitable Foundation.

    • Competing interests A-CM has received honoraria for participating in expert meetings from AstraZeneca. DZ reports grants from CSL Behring during the conduct of the study. IG reports grants from CSL Behring during the conduct of the study. PG reports grants from LFB during the conduct of the study. AG has received honoraria for participating in expert meetings from CSL Behring and LFB, and received travel fees for participating in expert meetings from AstraZeneca. No conflicts of interest reported for the remaining author.

    • Patient consent Obtained.

    • Ethics approval French Blood Bank Institute (Etablissement Français du Sang, Paris, France, convention ref. C CPSL UNT n°12/EFS/038).

    • Provenance and peer review Not commissioned; externally peer reviewed.