Background: Clonal hematopoiesis of indeterminate potential (CHIP) might contribute to the pathogenesis of immune thrombocytopenia (ITP) through immune dysfunction or impairment of megakaryopoiesis and platelet formation. However, little is known about subsequent risk of ITP among individuals with CHIP.

Objective: To investigate the risk of ITP among individuals with CHIP.

Methods: We investigated the association of CHIP with risk of ITP by a prospective cohort study, including 466,064 participants in the UK Biobank, during 2006 to 2022. CHIP was ascertained based on data of whole exome sequencing. Incident ITP was identified in inpatient hospital records and death register. Cox regression models were utilized to estimate risk of ITP associated with CHIP. We also performed subgroup analyses by CHIP mutations (DNMT3A, TET2, ASXL1, SRSF2, and JAK2).

Results: The study included 14,466 and 451,598 individuals with and without CHIP, respectively. We identified 34 and 390 cases of ITP among the CHIP group and the reference group, respectively. CHIP was associated with an increased risk of ITP (hazard ratio [HR] 2.33, 95% confidence interval [CI]: 1.64-3.32). Subgroup analysis revealed that the heightened risk of ITP was greatest in CHIP with JAK2 mutation (HR 54.31, 95% CI: 17.39-169.59), followed by CHIP with SRSF2 (HR 20.11, 95% CI: 8.27-48.87), TET2 (HR 4.00, 95% CI: 2.34-6.83), or DNMT3A (HR 1.95, 95% CI: 1.16-3.27) mutation.

Conclusions: CHIP was associated with an increased risk of being diagnosed with ITP, particularly for CHIP with JAK2 or SRSF2 mutation. These findings call for clinical awareness of the risk of ITP among individuals with CHIP.