骨髓衰竭相关种系变异患者孤立性血小板减少症的临床特征：一项单中心回顾性研究

Clinical characteristic of isolated thrombocytopenia in patients with bone marrow failure-related germline variants: a retrospective study from a single centre.

作者信息

Dong Nanxi, Dong Jingjie, Xin Chuanao, Wang Peicheng, Hong Yaonan, Zheng Rudan, Sun Zexing, Liu Qi, Shen Yingying, Yang Xiawan, Shen Yiping, Shen Jianping, Ye Baodong, Zhou Yuhong, Wu Dijiong

机构信息

Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China.

The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

出版信息

Ann Med. 2025 Dec;57(1):2523560. doi: 10.1080/07853890.2025.2523560. Epub 2025 Jun 26.

DOI:10.1080/07853890.2025.2523560

PMID:40574285

Abstract

BACKGROUND

Immune thrombocytopenia (ITP) comprises the majority of thrombocytopenia. Some patients respond poorly to first-line ITP therapy or develop pancytopenia years later. Recent studies link heterozygous germline variants in acquired aplastic anemia (AA), yet their role in isolated thrombocytopenia carrying bone marrow failure-related germline variants (ITGV-BMFs) remains unclear. While whole-exome sequencing (WES) detects these variants, its cost limits routine use. This study compares prognosis and clinical features of isolated thrombocytopenia in patients with ITGV-BMFsand those with classic ITP.

METHODS

The clinical data of patients diagnosed with ITGV-BMFs were retrospectively analyzed and compared with those of patients with classic ITP from August 2018 to February 2024. The baseline characteristics, genomic systematically background, previous treatment response as well as their follow-up outcomes were compared.

RESULTS

Patients with ITGV-BMFs demonstrated earlier onset age ( < 0.001), lower bleeding scores and CD34%, along with elevated mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and reticulocyte (RET) counts ( < 0.001). Multivariate logistic regression analysis showed that the patients with ITGV-BMFs may possess distinct characteristics, including an earlier age at onset ( = 0.014) and lower bleeding score ( = 0.048). Notably, MCV and RET showed promising performance in receiver operating characteristic (ROC) curve analysis. During the follow-up period, 57.69% (15/26) ITGV-BMFs patients were further confirmed as aplastic anemia (AA, = 13) or myelodysplastic syndrome (MDS, = 2), with a median progression-free survival (PFS) of 7.25 years ( < 0.0001).

CONCLUSION

ITGV-BMFs may be diagnosed early using elevated MCV and reticulocyte counts, a diagnostic approach that may lead to earlier intervention and improved prognosis.

摘要

背景

免疫性血小板减少症（ITP）是血小板减少症的主要类型。一些患者对一线ITP治疗反应不佳，或在数年后发展为全血细胞减少症。最近的研究将获得性再生障碍性贫血（AA）中的杂合种系变异联系起来，但其在携带骨髓衰竭相关种系变异的孤立性血小板减少症（ITGV-BMFs）中的作用仍不清楚。虽然全外显子测序（WES）可以检测到这些变异，但其成本限制了常规使用。本研究比较了ITGV-BMFs患者和经典ITP患者孤立性血小板减少症的预后和临床特征。

方法

回顾性分析2018年8月至2024年2月诊断为ITGV-BMFs的患者的临床资料，并与经典ITP患者的临床资料进行比较。比较了基线特征、基因组系统背景、既往治疗反应及其随访结果。

结果

ITGV-BMFs患者发病年龄较早（<0.001），出血评分和CD34%较低，同时平均红细胞体积（MCV）、平均红细胞血红蛋白（MCH）和网织红细胞（RET）计数升高（<0.001）。多因素logistic回归分析显示，ITGV-BMFs患者可能具有不同的特征，包括发病年龄较早（=0.014）和出血评分较低（=0.048）。值得注意的是，MCV和RET在受试者工作特征（ROC）曲线分析中表现出良好的性能。在随访期间，57.69%（15/26）的ITGV-BMFs患者被进一步确诊为再生障碍性贫血（AA，=13）或骨髓增生异常综合征（MDS，=2），无进展生存期（PFS）中位数为7.25年（<0.0001）。