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Observational Study
. 2025 Feb 11;9(3):488-495.
doi: 10.1182/bloodadvances.2024014984.

Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study

Bruno Fattizzo  1   2 , Alfredo Marchetti  1   2 , Alessandro Bosi  1   2 , Carmelo Gurnari  3   4 , Juri Alessandro Giannotta  1 , Giacinto Luca Pedone  1   2 , Elena Rossi  5 , Valentina Carrai  6 , Andrea Guido  2 , Filippo Brioschi  7 , Monica Carpenedo  8 , Monica Crugnola  9 , Domenica Caramazza  10 , Livia Leuzzi  11 , Monia Marchetti  12 , Gabriele Merati  13 , Simona Malato  14 , Fabrizio Vianello  15 , Andrea Patriarca  16 , Hussein Awada  4 , Marta Bortolotti  1 , Marta Canzi  1   2 , Niccolò Bolli  1   2 , Marco Capecchi  1   17 , Frederick Chen  18   19 , Andrea Artoni  1 , Jaroslaw P Maciejewski  4 , Wilma Barcellini  1
Affiliations
Observational Study

Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study

Bruno Fattizzo et al. Blood Adv. .

Abstract

Diagnostic boundaries between immune thrombocytopenia (ITP) and other thrombocytopenic states, such as thrombocytopenic myelodysplastic syndromes, may be difficult to establish, and the detection of somatic mutations by next-generation sequencing (NGS) may be of aid. Here, we aimed at characterizing the prevalence and clinical significance of clonal hematopoiesis in ITP. In this multicentric retrospective observational study, we enrolled 167 adult patients with ITP, followed at 13 centers in Italy, United Kingdom, and the United States. Patients underwent NGS evaluation after a median of 3.6 years from ITP onset, and 83% had received at least 1 therapy line, for a median of 2 lines (range, 0-9); 51 of 167 patients (30%) had at least 1 mutation. After exclusion of germ line variants and polymorphisms, 31 of 167 (18.5%) were defined as having clonal hemopoiesis. Most commonly mutated genes were TET2, DNMT3A, SRSF2, and ASXL1 (median variant allele frequency, 29%); 19 of 31 patients (68%) had high-risk variants, and 8 had multiple mutations. Mutated patients were more frequently older males and showed a shorter time from first to second-line therapy, particularly with thrombopoietin receptor agonist (TPO-RA). Additionally, clonal hematopoiesis was associated with increased thrombotic risk (26% vs 8% in NGS-negative cases; P = .01), independently from TPO-RA exposure, though with an age effect. These data demonstrated the prevalence of clonal hematopoiesis in 18% of adult patients with ITP, which is associated with older age, relapsed/refractory disease, and high risk of thrombotic complications.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Prevalence and type of somatic mutations in patients with ITP. (A) Oncoplot showing mutated genes, frequency, and allelic burden. (B) Association of clonal hemopoiesis with age in terms of cumulative incidence over age. The detail shows the age distribution in patients bearing CHIP mutations. TMB, total mutation burden.
Figure 2.
Figure 2.
Impact of clonal hematopoiesis on the time from diagnosis to thrombopoietin receptor agonist (TPO-RA) and to second-line treatment. (A) Time to thrombopoietin receptor agonists treatment according to NGS positivity for CHIP mutations. (B) Time to second-line treatment (any treatment option) in patients with ITP according to NGS positivity for CHIP mutations.
Figure 3.
Figure 3.
Association of high-risk clonal hemopoiesis with thrombosis in patients with ITP by multivariable analysis. High-risk clonal hemopoiesis as interpreted according to Stonestrom et al (blue lines) and Weeks et al (orange lines).
See this image and copyright information in PMC

References

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