Gradual increase in thrombogenicity of juvenile platelets formed upon offset of prasugrel medication

Constance C. F. M. J. Baaten, Leo F. Veenstra, Rick Wetzels, Johanna P. van Geffen, Frauke Swieringa, Susanne M. de Witt, Yvonne M. C. Henskens, Harry Crijns, Sven Nylander, J. J. J. van Giezen, Johan W. M. Heemskerk, Paola E. J. van der Meijden*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


In patients with acute coronary syndrome, dual antiplatelet therapy with aspirin and a P2Y(12) inhibitor like prasugrel is prescribed for one year. Here, we investigated how the hemostatic function of platelets recovers after discontinuation of prasugrel treatment. Therefore, 16 patients who suffered from ST-elevation myocardial infarction were investigated. Patients were treated with aspirin (100 mg/day, long-term) and stopped taking prasugrel (10 mg/day) after one year. Blood was collected at the last day of prasugrel intake and at 1, 2, 5, 12 and 30 days later. Platelet function in response to ADP was normalized between five and 30 days after treatment cessation and in vitro addition of the reversible P2Y(12) receptor antagonist ticagrelor fully suppressed the regained activation response. Discontinuation of prasugrel resulted in the formation of an emerging subpopulation of ADP-responsive platelets, exhibiting high expression of active integrin alpha(IIb)beta(3). Two different mRNA probes, thiazole orange and the novel 5'Cy5-oligo-dT probe revealed that this subpopulation consisted of juvenile platelets, which progressively contributed to platelet aggregation and thrombus formation under flow. During offset, juvenile platelets were overall more reactive than older platelets. Interestingly, the responsiveness of both juvenile and older platelets increased in time, pointing towards a residual inhibitory effect of prasugrel on the megakaryocyte level. In conclusion, the gradual increase in thrombogenicity after cessation of prasugrel treatment is due to the increased activity of juvenile platelets.
Original languageEnglish
Pages (from-to)1131-1138
JournalHaematologica-the Hematology Journal
Issue number9
Publication statusPublished - Sept 2015


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