Evaluation of the procoagulant state in chronic immune thrombocytopenia before and after eltrombopag treatment—a prospective cohort study

Wobke E.M. van Dijk, Geke C. Poolen, Albert Huisman, Harry R. Koene, Rob Fijnheer, Noortje Thielen, Esther R. van Bladel, Karin P.M. van Galen, Roger E.G. Schutgens, Rolf T. Urbanus*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Thrombopoietin receptor agonists are frequently used in treating immune thrombocytopenia (ITP) owing to high response rates and good tolerability. ITP is associated with an increased risk of thrombosis. Whether treatment with eltrombopag further increases this risk is controversial. The mechanisms behind the thrombotic risk in ITP are unclear. Objectives: To assess platelet function and hypercoagulability in patients with ITP and the effect of eltrombopag thereon. Methods: This prospective multicenter study assessed adult primary patients with ITP who were starting eltrombopag treatment. Platelet (re)activity and hypercoagulability were measured in whole blood or plasma before start and after 2 to 3 weeks of eltrombopag treatment and compared with those of controls. Change over time was assessed by mixed-effects models, and the results were corrected for multiple testing. Results: We included 16 patients and 33 controls. At baseline, patients with ITP exhibited lower expression of glycoprotein VI, more activated platelets, and lower reactivity toward agonists compared with controls. β-Thromboglobulin levels reduced and thrombin generation peak height increased compared with those of controls. In line with this finding, patients with ITP showed high factor VIII (median, 217%; IQR, 174%-272%) and von Willebrand factor levels (median, 167%; IQR, 109%-198%). Eltrombopag treatment increased thrombin generation potential: lag time decreased and peak height and endogeneous thrombin potential increased. The latter changes were not significant after correction for multiple testing. Conclusion: Patients with ITP in this study were in a hypercoagulable state, with preactivated platelets, increased thrombin generation potential, and increased levels of factor VIII and von Willebrand factor. Eltrombopag treatment further increased plasma thrombin generation potential but no other hemostatic parameters.

Original languageEnglish
Pages (from-to)1020-1031
Number of pages12
JournalJournal of Thrombosis and Haemostasis
Volume21
Issue number4
DOIs
Publication statusPublished - Apr 2023

Keywords

  • eltrombopag
  • ITP
  • procoagulant
  • thrombosis
  • TPO-RA

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