结合出血评分、表型实验室分析和下一代测序对克罗地亚儿科队列血管性血友病诊断的重新评估:一项试点研究

IF 3.8 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY
Ivana Lapić, Margareta Radić Antolic, Sara Dejanović Bekić, Désirée Coen-Herak, Ernest Bilić, Dunja Rogić, Renata Zadro
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引用次数: 1

摘要

本研究通过结合出血评分(BS)、表型实验室检测和下一代测序(NGS),重新评估克罗地亚儿科队列中的血管性血友病(vWD)诊断。材料和方法:纳入既往诊断为vWD的儿童25例(男11例,女14例,中位年龄10岁,2 ~ 17岁)。使用在线出血评估工具计算BS。表型实验室分析包括血小板计数、血小板功能分析仪关闭时间、凝血酶原时间、活化的部分凝血酶时间、血管性血友病因子抗原(vWF:Ag)、vWF功能获得型突变糖蛋白Ib结合活性(vWF:GPIbM)、vWF胶原结合活性(vWF:CBA)、因子VIII活性(FVIII:C)和多聚体分析。下一代测序覆盖了vWF和FVIII基因的区域,并在MiSeq (Illumina, San Diego, USA)上进行。结果:在15例患者中发现的疾病相关变异体包括13例患者中11种不同的杂合vWF基因变异体和2例男性兄弟姐妹中1种新的FVIII基因变异体(p.Glu2085Lys)。4个vWF变异是新发现的(p.Gln499Pro, p.Asp1277Tyr, p.Asp1277His, p.Lys1491Glu)。三名无明显变异的患者的vWF:GPIbM在30 - 50%之间。发现vWF基因变异的患者vWF:GPIbM (P = 0.002)、vWF:Ag (P = 0.007)、vWF:CBA (P < 0.001)和FVIII:C (P = 0.002)值均低于未发现vWF基因变异的患者。BS与表型实验室测试结果之间的相关性在两项测试中均无统计学意义。结论:应用诊断方法确诊vWD 13例,轻度A型血友病2例。证明了BS在儿科人群中的有限效用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Reevaluation of von Willebrand disease diagnosis in a Croatian paediatric cohort combining bleeding scores, phenotypic laboratory assays and next generation sequencing: a pilot study.

Introduction: This study reevaluated von Willebrand disease (vWD) diagnosis in a Croatian paediatric cohort by combining bleeding scores (BS), phenotypic laboratory testing, and next-generation sequencing (NGS).

Materials and methods: A total of 25 children (11 males and 14 females, median age 10 years, from 2 to 17) previously diagnosed with vWD were included. BS were calculated using an online bleeding assessment tool. Phenotypic laboratory analyses included platelet count, platelet function analyser closure times, prothrombin time, activated partial thromboplastin time, von Willebrand factor antigen (vWF:Ag), vWF gain-of-function mutant glycoprotein Ib binding activity (vWF:GPIbM), vWF collagen binding activity (vWF:CBA), factor VIII activity (FVIII:C) and multimeric analysis. Next-generation sequencing covered regions of both vWF and FVIII genes and was performed on MiSeq (Illumina, San Diego, USA).

Results: Disease-associated variants identified in 15 patients comprised 11 distinct heterozygous vWF gene variants in 13 patients and one novel FVIII gene variant (p.Glu2085Lys) in two male siblings. Four vWF variants were novel (p.Gln499Pro, p.Asp1277Tyr, p.Asp1277His, p.Lys1491Glu). Three patients without distinctive variants had vWF:GPIbM between 30 and 50%. Patients with identified vWF gene variants had statistically significant lower values of vWF:GPIbM (P = 0.002), vWF:Ag (P = 0.007), vWF:CBA (P < 0.001) and FVIII:C (P = 0.002), compared to those without. Correlations between BS and phenotypic laboratory test results were not statistically significant for either of the tests.

Conclusion: The applied diagnostic approach confirmed the diagnosis of vWD in 13 patients and mild haemophilia A in two. Limited utility of BS in the paediatric population was evidenced.

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来源期刊
Biochemia Medica
Biochemia Medica 医学-医学实验技术
CiteScore
5.50
自引率
3.00%
发文量
70
审稿时长
>12 weeks
期刊介绍: Biochemia Medica is the official peer-reviewed journal of the Croatian Society of Medical Biochemistry and Laboratory Medicine. Journal provides a wide coverage of research in all aspects of clinical chemistry and laboratory medicine. Following categories fit into the scope of the Journal: general clinical chemistry, haematology and haemostasis, molecular diagnostics and endocrinology. Development, validation and verification of analytical techniques and methods applicable to clinical chemistry and laboratory medicine are welcome as well as studies dealing with laboratory organization, automation and quality control. Journal publishes on a regular basis educative preanalytical case reports (Preanalytical mysteries), articles dealing with applied biostatistics (Lessons in biostatistics) and research integrity (Research integrity corner).
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