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Effect of thrombopoietin receptor agonists on leukocyte and haematopoietic stem and progenitor cells in the peripheral blood of patients with immune thrombocytopenic purpura

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Abstract

The thrombopoietin receptor agonists (TPO-RAs), romiplostim and eltrombopag, stimulate megakaryopoiesis and thereby increase platelet counts. Both drugs are increasingly used in the treatment of immune thrombocytopenic purpura (ITP). To assess the effect of TPO-RAs on trilineage haematopoiesis, colony-forming cell (CFC) assays were performed on peripheral blood mononuclear cells of 8 healthy donors and 52 ITP patients. Additionally, we revaluated the regular and complete blood counts (CBCs) performed during romiplostim therapy in 45 patients and the CBCs performed in 9 patients during eltrombopag therapy. The clonogenic capacity of PBMCs was significantly increased in patients treated with TPO-RAs compared with healthy donors and untreated patients [BFU-E, 69 ± 47; CFU-GM, 61 ± 48; CFU-GEMM, 16 ± 11; CFU-total, 145 ± 94; P values < 0.05)]. Relative leukocytosis was observed in routine blood counts in 12 of 45 (26%) patients treated with romiplostim. The regular CBCs, performed time dependent within the first 5 days, revealed a maximum increase of leukocytes on days 2 and 3 following romiplostim administration. There were no significant changes in red blood cell parameters. None of the affected patients did recognise any significant symptom, which may be related to leukocytosis. Similarly, we observed a statistically significant increase of leukocyte count in a small cohort of ITP patients (n = 9) in whom CBCs were controlled following treatment initiation (P = 0.044). Our results indicate that TPO-RAs may also mobilize haematopoietic stem and progenitor cells (HSPCs) in peripheral blood and the occurrence of such relative leukocytosis may signalize an early symptom of myelofibrosis due to treatment with TPO-RAs.

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  1. Gürkan Bal and Depré Fabian contributed equally to this work.

Authors and Affiliations

  1. Institute of Integrative Neuroanatomy, Charité – Universitatsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Gürkan Bal

  2. Institute of Transfusion Medicine, Charité – Universitatsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Gürkan Bal, Depré Fabian, Dzamashvili Maia, Frauke Ringel & Abdulgabar Salama

  3. Department of Cardiology and Pneumology, Campus Benjamin Franklin, Charité – Universitatsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany

    Depré Fabian

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Contributions

GB, FD, and AS designed the research study. FD and FR collected and performed an illustration of clinical data. MD and GB performed experiments. GB and FD performed data analysis. GB, FD, and AS wrote the manuscript. MD and FR critically revised the manuscript. AS supervised the work. All authors gave permission for the final version prior to submission.

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Correspondence to Gürkan Bal.

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This study was approved by the institutional ethics review board (EA2/058112). Informed consent was obtained from all patients for being included in the study.

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The authors declare that they have no conflicts of interest.

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Bal, G., Fabian, D., Maia, D. et al. Effect of thrombopoietin receptor agonists on leukocyte and haematopoietic stem and progenitor cells in the peripheral blood of patients with immune thrombocytopenic purpura. Ann Hematol 96, 2045–2056 (2017). https://doi.org/10.1007/s00277-017-3131-6

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