Association between megakaryocyte abnormalities on bone marrow smear and response to thrombopoietin receptor agonists in adult patients with primary immune thrombocytopenia

Abstract

Impaired platelet production is a mechanism of immune thrombocytopenia (ITP). Morphological abnormalities of megakaryocytes (MKs) are sometimes observed in this disease. Two studies have suggested an association between MK abnormalities and response to corticosteroids in primary ITP, but none have investigated this association for thrombopoietin-receptor agonists (TPO-RAs). This was the aim of this study. The source of population was the French CARMEN registry with prospective follow-up of adult patients with incident ITP. We included patients with primary ITP, treated by TPO-RA and with a bone marrow smear before initiating TPO-RA. MK abnormalities were categorized by the presence of dysplasia and by the stage of maturation. Among 451 patients screened, 38 were included in the analysis. There was no difference in the median percentage of dysplastic MKs between responders to TPO-RA (4.0%, 95% confidence interval – CI: 2.3–6.4) and non-responders (4.5%, 95% CI: 0.7–7.1). There was a slightly higher proportion of granular MKs (4.5%, 95% CI: 3–6) and basophilic MKs (30.1%, 95% CI: 21.9–39.1) in non-responders compared to responders (granular: 2.0%, 95% CI: 0–4.1; basophilic: 21.3%, 95% CI: 11.4–40.7). In conclusion, MK abnormalities were not associated with response achievement in ITP patients treated with TPO-RA in this series of 38 patients.

Keywords:

• Immune thrombocytopenia
• megakaryocytes
• thrombopoietin receptor agonist

Acknowledgements

This was an academic study. We thank all the investigators of CARMEN study group. The CARMEN registry received support from the French national society of internal medicine, Toulouse referral center for autoimmune cytopenias, Toulouse University Hospital, Amgen, CSL Behring, Grifols, and Novartis.

Disclosure statement

This study was academic. GM received meeting attendance grants from Amgen and Novartis, is coordinator of research studies granted by Amgen, CSL Behring, Grifols, Novartis, and Sanofi. He participated to educational sessions funded by Amgen, Grifols, and Novartis, and to boards for Amgen, Argenx, Novartis, and Sobi. TC received honoraria and/or research or educational support from AbbVie, AstraZeneca, Bristol Myers Squibb (Celgene), Novartis, and Takeda. All other authors declare having no competing interest.

Contributions

OW and GM designed the study, analyzed the clinical data, conducted the statistical analyses and wrote the manuscript. AR, JBR and VDM analyzed the bone marrow smears. All other authors contributed to data acquisition, critically reviewed the manuscript and gave final approval for publication.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.