Whole transcriptome analysis reveals T cell signaling activation in septic patients with thrombocytopenia

Sepsis, a life-threatening condition triggered by a dysregulated immune response to infection, remains one of the leading causes of mortality worldwide. Thrombocytopenia, a common sepsis complication, is linked to poor outcomes and reflects disease severity and specific immunological changes affecting patient outcomes. This study aimed to investigate transcriptomic differences between septic patients with and without thrombocytopenia and to explore immune features related to clinical outcomes using whole-transcriptome RNA sequencing (RNA-Seq). We conducted a prospective study on 52 patients who were admitted to ICU for sepsis, including 22 with thrombocytopenia and 30 without. Blood samples were collected on both day 1 and 8, and RNA-Seq was performed to analyze transcriptomic profiles. Differentially expressed genes (DEGs) were identified, and functional enrichment analyses were conducted to explore biological pathways and processes. T-cell receptor (TCR) diversity was assessed using MiXCR and VDJTools software. Thrombocytopenic critically ill septic patients exhibited significantly higher Sequential Organ Failure Assessment (SOFA) scores and mortality rates compared to non-thrombocytopenic patients. Transcriptomic analysis revealed distinct gene expression profiles between the two groups, with marked upregulation of myeloproliferative and T-cell activation signaling pathways in thrombocytopenic patients on day 1. Additionally, TCR diversity counts showed no statistically significant differences between thrombocytopenic and non-thrombocytopenic patients at day 1 or day 8. Thrombocytopenia in septic ICU patients is associated with altered heme/porphyrin metabolism, erythrocyte development, and immune activation. Lower TCR diversity on day 1 in thrombocytopenic patients suggests early immune repertoire perturbations; however, these findings should be interpreted cautiously and validated with targeted immune repertoire sequencing.