ORIGINAL RESEARCH article

Front. Immunol.

Sec. Cytokines and Soluble Mediators in Immunity

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1589996

This article is part of the Research TopicCytokine Interactions and Biomarker Potential in Various DiseasesView all articles

Markers of Endothelial Damage, Platelet Activation, and Inflammation in Platelet Transfusion Refractoriness: Clinical outcomes in Pediatric Cancer Patients with Thrombocytopenia

Provisionally accepted
Chao  ZhouChao Zhou1Jun  XuJun Xu1Jihua  MaJihua Ma1Junjie  LinJunjie Lin2Huilin  WangHuilin Wang2Xuejun  ChenXuejun Chen1*
  • 1The Children's Hospital, School of Medicine, Graduate School, Zhejiang University, Hangzhou, China
  • 2School of Medical Technology and lnformation Engineering, Zhejiang Chinese Medical University, Hangzhou, Jiangsu Province, China

The final, formatted version of the article will be published soon.

Platelet transfusion refractoriness (PTR) is a significant issue in pediatric oncology patients with chemotherapy-induced thrombocytopenia (CIT), its non-immune mechanisms remain poorly understood currently. This study investigated potential changes in endothelial damage, platelet activation, and associated inflammatory mediators in PTR and their association with clinical outcomes.We enrolled 36 patients with PTR and 38 patients with Non-PTR. Plasma markers of endothelial damage, platelet activation, and inflammation were measured pre-transfusion using flow cytometry and ELISA. Median levels of sP-selectin, sCD40L, vWF, IL-1β, and IL-8 were significantly higher in the PTR group.Multivariate analysis identified IL-1β and IL-8 as independent risk factors for PTR. ROC analysis revealed AUCs of 0.712 (sP-selectin), 0.654 (sCD40L), 0.662 (vWF), 0.651 (IL-1β), and 0.690 (IL-8).PTR patients had longer platelet count recovery days (10.2 days vs.7.3 days), more bleeding events (36.1% vs. 13.2%), and lower 500-day progression-free survival (PFS) rates (41.5% vs. 55.2%). High sP-selectin (≥ 10.1 ng/mL) and sCD40L (≥ 234.5 pg/mL) levels were associated with increased bleeding risk. High levels of sCD40L (≥ 234.5 pg/mL) and IL-8 (≥ 91.3 pg/mL) had significantly lower 500-day PFS rates, 41.4% vs 84.2%, and 49.7% vs 77.2%, respectively. Cox regression confirmed sCD40L and IL-8 as independent predictors of reduced PFS rates. These findings highlight endothelial damage, platelet activation, and inflammation as critical mechanisms underlying PTR and association with clinical outcomes. It has potential value as predictive markers and to adjust supportive care treatment and to develop novel preventive or therapeutic strategies in pediatric patients with CIT.

Keywords: Platelet transfusion refractoriness, Endothelial damage, Platelet Activation, Inflammatory, outcomes

Received: 08 Mar 2025; Accepted: 06 Jun 2025.

Copyright: © 2025 Zhou, Xu, Ma, Lin, Wang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Xuejun Chen, The Children's Hospital, School of Medicine, Graduate School, Zhejiang University, Hangzhou, China

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