Abnormal Platelet Counts and Clonal Hematopoiesis in the General Population

Priscilla Kamphuis, Maaike G.J.M. Van Bergen, Isabelle A. Van Zeventer, Aniek O. De Graaf, Avinash G. Dinmohamed, Jonas B. Salzbrunn, Jan Jacob Schuringa, Bert A. Van Der Reijden, Gerwin Huls*, Joop H. Jansen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Clonal hematopoiesis (CH) is defined by the presence of somatic mutations that may cause clonal expansion of hematopoietic cells. Here, we investigated the association between platelet count abnormalities, CH and consequences on overall survival and the development of hematological malignancies. Individuals with thrombocytopenia (n = 631) or thrombocytosis (n = 178) ≥60 years, and their age- and sex-matched controls, were selected within the population-based Lifelines cohort (n = 167,729). Although the prevalence of CH was not increased in thrombocytopenia cases compared with their controls (37.9% vs 39.3%; P = 0.639), mutations in spliceosome genes (SF3B1, SRSF2, U2AF1) were significantly enriched in thrombocytopenia cases (P = 0.007). Overall, CH in combination with thrombocytopenia did not impact on survival, but thrombocytopenia in combination with multiple mutated genes (hazard ratio [HR] = 2.08, 95% confidence interval [CI], 1.24-3.50; P = 0.006), mutations in TP53 (HR = 5.83, 95% CI, 2.49-13.64; P < 0.001) or spliceosome genes (HR = 2.69, 95% CI, 1.29-5.63; P = 0.009) increased the risk of death. The prevalence of CH in thrombocytosis cases was higher compared with controls (55.8% vs 37.7%; P < 0.001). Especially mutations in JAK2 (P < 0.001) and CALR (P = 0.003) were enriched in individuals with thrombocytosis. The presence of CH in individuals with thrombocytosis did not impact on overall survival. However, during follow-up of 11 years 23% of the individuals with thrombocytosis and CH were diagnosed with hematological malignancies. From these, 81% were diagnosed with myeloproliferative disease and 76% carried driver mutations JAK2, CALR, or MPL.

Original languageEnglish
Pages (from-to)E821
Issue number1
Publication statusPublished - Jan 2023

Bibliographical note

Funding Information:
This work was supported by the MDS-RIGHT project, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement 634789. The funder of this study had no role in study design, collection, analysis, and interpretation of data, and writing or approval of the manuscript. The Lifelines Biobank initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport; the Dutch Ministry of Economic Affairs; the University Medical Center Groningen; University Groningen; and the Northern Provinces of The Netherlands. AOdG and JHJ were supported by a grant from the Dutch Cancer Society (grant number 10813).

Publisher Copyright:
© 2023 the Author(s). Published by Wolters Kluwer Health, Inc.


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