RNA sequencing indicates distinct platelet transcriptomic changes in immune thrombocytopenia

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BACKGROUND: In immune thrombocytopenia (ITP), platelet-intrinsic alterations and their potential contribution to disease pathogenesis remain incompletely understood. Since platelets, although anucleate, retain a functional transcriptome, transcriptomic profiling may provide insight into disease-associated changes. OBJECTIVES: To investigate platelet-intrinsic transcriptomic changes in ITP and to determine whether these alterations are disease-specific compared with non-ITP. METHODS: Total RNA sequencing was performed on purified platelets from patients with active ITP (n = 6), chemotherapy-induced thrombocytopenia as a non-ITP control (n = 6), ITP in treatment-free remission (n = 6), and healthy controls (n = 8). RESULTS: Platelets from patients with active ITP exhibited higher total RNA content, consistent with enrichment of young, recently released platelets. Transcriptomic analysis identified a profile dominated by platelet activation pathways, including integrin- and calcium-dependent signaling, cytoskeletal remodeling, and vesicle trafficking. In contrast, genes involved in mitochondrial biogenesis and oxidative phosphorylation were downregulated, accompanied by a reduced proportion of mitochondrial-derived RNA. Although both active ITP and chemotherapy-induced thrombocytopenia showed elevated RNA content relative to healthy controls, reflecting enhanced platelet turnover, the coordinated upregulation of activation-associated transcripts was unique to active ITP. Platelets from ITP patients in treatment-free remission showed partial normalization of the transcriptional profile, with loss of the activation signature and intermediate expression patterns between active ITP and healthy controls. CONCLUSION: RNA sequencing data show distinct platelet transcriptomic changes in ITP, marked by coordinated upregulation of platelet activation pathways and reduced mitochondrial gene expression. This profile is consistent with an activation-primed, metabolically altered platelet state and may reflect disease-related changes in platelet biology in ITP.

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