诊断为各种遗传性血小板疾病的患者的临床和实验室方面

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-05-01 DOI:10.1016/j.rpth.2025.102873

Veysel Gök , Alper Ozcan , Fatma Türkan Mutlu , Ebru Yılmaz , Deniz Kocak Göl , Mustafa Ozay , Baver Demir , Hüseyin Taskiran , Hasan Bas , Mehmet Burak Mutlu , Muhammet Ensar Dogan , Atil Bisgin , Ido Somekh , Meino Rohlfs , Munis Dundar , Yusuf Ozkul , Christoph Klein , Musa Karakukcu , Ekrem Unal

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引用次数: 0

摘要

背景：遗传性血小板疾病（IPDs）以血小板减少、血小板功能障碍或两者兼而有之为特征，可导致复发性出血和诊断困难。基因检测的进步大大提高了早期和准确的诊断。本研究旨在评估ipd的临床和遗传谱，确定诊断挑战，并评估治疗干预的结果。方法对50例IPD患者进行回顾性队列研究。我们进行了临床评估、外周涂片分析和基因检测，以确定致病变异。分析血小板计数、出血严重程度和治疗效果（如造血干细胞移植和血小板生成素受体激动剂）之间的相关性。结果54.5%的病例表现为常染色体显性遗传。诊断延迟是常见的，许多患者最初被误诊为患有免疫性血小板减少性紫癜（ITP）。血小板计数与出血严重程度之间存在中度、负的、统计学上显著的相关性。外周涂片结果，如口腔细胞增生和巨血小板减少症，提供了关键的诊断线索。我们发现了GP1BA、ITGB3、NBEAL2、WAS和MPL基因的新突变，这扩大了我们对ipd的理解。采用不同的治疗方式。在严重的全身性病例，如Wiskott-Aldrich综合征，进行造血干细胞移植。用依折麦布治疗谷甾醇血症。血小板生成素受体激动剂减少了一些患者的出血。结论综合遗传学、临床和实验室结果对IPDs的准确诊断和治疗至关重要。早期基因诊断和个性化治疗策略可改善预后。未来的研究应侧重于新突变的功能研究和改进治疗方案，以加强对这一复杂人群的护理。

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Clinical and laboratory aspects of patients diagnosed with various inherited platelet disorders

Background

Inherited platelet disorders (IPDs) are characterized by thrombocytopenia, platelet dysfunction, or both, leading to recurrent bleeding and diagnostic challenges. Advances in genetic testing have significantly improved early and accurate diagnoses.

Objectives

This study aimed to evaluate the clinical and genetic spectrum of IPDs, identify diagnostic challenges, and assess outcomes of therapeutic interventions.

Methods

We conducted a retrospective cohort study of 50 IPD patients. We performed clinical evaluations, peripheral smear analyses, and genetic testing to identify causative variants. Correlation between platelet counts, bleeding severity, and the effectiveness of treatments, such as hematopoietic stem cell transplantation and thrombopoietin receptor agonists, was analyzed.

Results

A total of 54.5% of cases showed autosomal dominant inheritance. Diagnostic delays were common, with many patients initially misdiagnosed as having immune thrombocytopenic purpura (ITP). There was a moderate, negative, statistically significant correlation between platelet counts and bleeding severity. Peripheral smear findings, such as stomatocytosis and macrothrombocytopenia, provided critical diagnostic clues. We identified novel mutations in GP1BA, ITGB3, NBEAL2, WAS, and MPL genes, which expanded our understanding of IPDs. Different treatment modalities were used. Hematopoietic stem cell transplantation was performed in severe systemic cases, such as Wiskott–Aldrich syndrome. Sitosterolemia was treated with ezetimibe. Thrombopoietin receptor agonists reduced bleeding in some patients.

Conclusion

Integrating genetic, clinical, and laboratory findings is essential in providing accurate diagnoses and management of IPDs. Early genetic diagnosis and personalized therapeutic strategies improve outcomes. Future research should focus on functional studies of novel mutations and refining treatment protocols to enhance care for this complex population.

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