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.