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青少年女性月经过多的新型实验室方法学研究与血小板功能检测的初步研究

Pilot study of novel lab methodology and testing of platelet function in adolescent women with heavy menstrual bleeding.

机构信息

Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon.

Department of Pediatrics, The Hemophilia Center, Oregon Health and Science University, Portland, Oregon.

出版信息

Pediatr Res. 2018 Mar;83(3):693-701. doi: 10.1038/pr.2017.298. Epub 2018 Jan 3.

Abstract

BackgroundApproximately 40% of adolescent women experience heavy menstrual bleeding (HMB), and 10-62% of them have an underlying bleeding disorder (BD). Diagnosing a BD remains challenging because of limitations of available clinical platelet function assays. The aim of this study was to characterize platelet function in a population of adolescent women with HMB using small-volume whole-blood assays.MethodsAnticoagulated whole blood was used to assess platelet GPIIbIIIa activation, α-granule secretion, and aggregation in response to multiple agonists. Platelet adhesion on collagen or von Willebrand Factor (VWF) under static and shear flow was also assessed.ResultsFifteen participants with HMB were included in the study, of which eight were diagnosed with a clinically identifiable BD. Platelet activation was blunted in response to calcium ionophore in participants without a BD diagnosis compared with that in all other participants. Impaired GPIIbIIIa activation was observed in response to all GPCR agonists, except adenosine diphosphate (ADP), in participants with qualitative platelet disorders. Our assays detected platelet aggregation in the majority of participants with a BD in response to ADP, collagen-related peptide (CRP), thrombin receptor activator 6 (TRAP-6), or U46619. Platelet adhesion and aggregation on collagen and VWF was decreased for participants with VWD.ConclusionParticipants with and without BD exhibited aberrant platelet function in several assays in response to select agonists.

摘要

背景

约 40%的青春期女性经历月经过多(HMB),其中 10-62%存在潜在的出血性疾病(BD)。由于现有临床血小板功能检测的局限性,诊断 BD 仍然具有挑战性。本研究旨在使用小体积全血检测方法,对 HMB 青春期女性的血小板功能进行特征分析。

方法

使用抗凝全血评估血小板 GPIIbIIIa 激活、α-颗粒分泌和对多种激动剂的聚集反应。还评估了在静态和切变流条件下胶原或血管性血友病因子(VWF)上的血小板黏附。

结果

本研究纳入了 15 名 HMB 参与者,其中 8 名被诊断为具有临床可识别的 BD。与所有其他参与者相比,无 BD 诊断的参与者对钙离子载体的反应中血小板激活被削弱。在有定性血小板疾病的参与者中,除了二磷酸腺苷(ADP)外,所有 GPCR 激动剂均观察到 GPIIbIIIa 激活受损。我们的检测方法在大多数有 BD 的参与者中检测到 ADP、胶原相关肽(CRP)、血栓素受体激活剂 6(TRAP-6)或 U46619 诱导的血小板聚集。VWD 参与者的胶原和 VWF 上的血小板黏附和聚集减少。

结论

有和没有 BD 的参与者在几种对选定激动剂的反应中表现出异常的血小板功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26cb/5902421/aa76f4cd6471/nihms920400f1.jpg

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