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Effect of thrombopoietin receptor agonists on markers of coagulation and P-selectin in patients with immune thrombocytopenia.

  • Garabet, Lamya1, 2
  • Ghanima, Waleed2, 3, 4
  • Monceyron Jonassen, Christine1
  • Skov, Vibe5
  • Holst, René3, 6
  • Mowinckel, Marie-Christine7, 8
  • C Hasselbalch, Hans9
  • A Kruse, Torben10
  • Thomassen, Mads10
  • Liebman, Howard11
  • Bussel, James B12
  • Sandset, Per Morten2, 7, 8
  • 1 a Center for Laboratory Medicine , Østfold Hospital Trust , Kalnes , Oslo , Norway. , (Norway)
  • 2 b Institute of Clinical Medicine , University of Oslo , Norway. , (Norway)
  • 3 c Department of Research , Østfold Hospital Trust , Kalnes , Norway. , (Norway)
  • 4 d Department of Medicine , Østfold Hospital Trust , Kalnes , Norway. , (Norway)
  • 5 e Department of Hematology , Zealand University Hospital , Roskilde , Denmark. , (Denmark)
  • 6 f Oslo Centre for Biostatistics and Epidemiology , University of Oslo and Oslo University Hospital , Oslo , Norway. , (Norway)
  • 7 g Department of Haematology , Oslo University Hospital , Oslo , Norway. , (Norway)
  • 8 h Research Institute of Internal Medicine , Oslo University Hospital , Oslo , Norway. , (Norway)
  • 9 i Department of Hematology , Copenhagen University Hospital , Roskilde , Denmark. , (Denmark)
  • 10 j Department of Clinical Genetics , Odense University Hospital , Odense , Denmark. , (Denmark)
  • 11 k Department of Medicine , University of California-Keck School of Medicine , Los Angeles , CA , USA.
  • 12 l Department of Pediatrics, Division of Hematology , New York Presbyterian Hospital, Weill Cornell Medicine , New York , USA.
Published Article
Informa UK (Taylor & Francis)
Publication Date
Jan 01, 2019
DOI: 10.1080/09537104.2017.1394451
PMID: 29215956


Thrombopoietin-receptor-agonists (TPO-RA) are effective treatments of immune thrombocytopenia (ITP). Previous long-term TPO-RA clinical trials have shown that thrombotic events occurred in 6% of TPO-RA-treated ITP patients. To explore the increased risk of thrombosis, the effects of TPO-RA on markers of coagulation and P-selectin were studied. The study comprised two ITP cohorts and controls. Cohort 1 included 26 patients with sequential samples acquired before and during treatment with TPO-RA. Cohort 2 included a single sample in 18 patients on TPO-RA for more than one year. Thrombin generation (endogenous thrombin potential (ETP)) prothrombin fragments 1 + 2 (F1+2), D-dimer, and plasminogen-activator-inhibitor-1 (PAI-1) were measured as well as soluble P-selectin (sP-selectin). Sequential expression of encoding genes for P-selectin (SELP) and PAI-1 (SERPINE1) was determined in four patients in cohort 1. Significantly higher levels of F1+2, D-dimer, and PAI-1 were found in ITP patients before TPO-RA treatment and in patients on long-term TPO-RA treatment than in controls. Pre-treatment levels of sP-selectin did not differ from controls. Analysis of longitudinal trends showed an increase in platelet count, sP-selectin, and PAI-1 after initiation of TPO-RA, followed by gradual decline. Platelet count and sP-selectin remained at higher levels throughout the study, whereas PAI-1 did not. Levels of other studied parameters did not show significant changes after initiation of treatment. Expression of SELP was up-regulated after initiation of TPO-RA, while the expression of SERPINE1 showed no significant changes. In conclusion, elevated pre-treatment levels of F1+2, D-dimer and PAI-1 are compatible with ITP being an intrinsically pro-thrombotic condition. After TPO-RA treatment, there were no significant changes in markers of coagulation activation or fibrinolysis, except for an initial increase in PAI-1 and a significant increase in sP-selectin both of which may contribute to increased thrombotic risk associated with TPO-RA treatment in ITP.

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