Center of Thrombosis and Hemostasis, Kansai Medical University Medical Center, Moriguchi, Japan.
First Department of Internal Medicine, Kansai Medical University Medical Center, Moriguchi, Japan.
Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231193398. doi: 10.1177/10760296231193398.
Thrombotic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly impact transplant outcomes. We focused on high mobility group box-protein (HMGB)1, one causative agent of thrombotic lesions in allo-HSCT, and investigated its association with platelets. We statistically analyzed available data from 172 patients with hematopoietic malignancies receiving allo-HSCT. A significant enhancement of monocyte-chemotactant protein-1, HMGB1, and platelet-derived microparticle (PDMP) levels was observed at day 0 after transplantation as compared to pre-transplantation. Multivariate analysis of the association among HMGB1 and 16 factors on day 0 revealed a significant correlation of HMGB1 levels with thrombin-antithrombin complex, interleukin-6, and PDMPs. High mobility group box-protein 1-induced procoagulant platelet induction and PDMP generation were performed in vitro using healthy platelets. High mobility group box-protein 1-induced PDMP generation was suppressed by toll-like receptor inhibitors and recombinant thrombomodulin. These results suggest that HMGB1 contributes to platelet activation in patients after allo-HSCT and is associated with PDMP-related thrombotic complications.
异基因造血干细胞移植（allo-HSCT）后的血栓并发症显著影响移植结果。我们专注于高迁移率族蛋白 B1（HMGB1），它是 allo-HSCT 中血栓病变的一个原因，并研究了它与血小板的关系。我们对接受 allo-HSCT 的 172 例血液恶性肿瘤患者的可用数据进行了统计分析。与移植前相比，移植后第 0 天观察到单核细胞趋化蛋白-1（MCP-1）、HMGB1 和血小板衍生微颗粒（PDMP）水平显著升高。对移植后第 0 天 HMGB1 与 16 个因素之间的相关性进行多变量分析表明，HMGB1 水平与凝血酶-抗凝血酶复合物、白细胞介素-6 和 PDMP 呈显著相关。使用健康血小板在体外进行了 HMGB1 诱导的促凝血小板诱导和 PDMP 生成。TLR 抑制剂和重组血栓调节蛋白抑制了 HMGB1 诱导的 PDMP 生成。这些结果表明，HMGB1 有助于 allo-HSCT 后患者的血小板活化，并与 PDMP 相关的血栓并发症有关。
