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Reevaluation of platelet function in chronic immune thrombocytopenia: impacts of platelet size, platelet-associated anti-αIIbβ3 antibodies and thrombopoietin receptor agonists.
British Journal of Haematology ( IF 5.1 ) Pub Date : 2020-02-27 , DOI: 10.1111/bjh.16439
Nobuko Nishiura 1 , Hirokazu Kashiwagi 1 , Keigo Akuta 1 , Satoru Hayashi 1 , Hisashi Kato 1 , Yuzuru Kanakura 1 , Yoshiaki Tomiyama 1, 2
Affiliation  

Platelet function of immune thrombocytopenia (ITP) has been controversial because of methodological problems associated with low platelet counts. In this study, we evaluated platelet function in 21 patients with chronic ITP (cITP) using the recently developed flow cytometry (FCM)-based platelet aggregation assay (FCA) along with a PAC1/CD62P assay. Since ITP platelets are larger than controls, whole platelets (whole gating method) and size-adjusted platelets (size-adjusted method) were analysed in the PAC1/CD62P via FCM. We found that: (i) aggregation was equivalent [phorbol myristate acetate (PMA) or adenosine diphosphate (ADP)-induced] or enhanced [protease-activated receptor 1-activating peptide (PAR1AP)-induced] in cITP compared with control by FCA; (ii) PAC1 or CD62P was also equivalent or enhanced in cITP in the whole gating method; and (iii) in sharp contrast, the size-adjusted method revealed that ADP-, PAR1AP-, and collagen synthetic liquid reactive peptide (SRP)-induced PAC1 and ADP-induced CD62P were impaired in cITP. These data suggested that an increase in the number of larger-sized platelets may compensate for the impaired platelet function of cITP, leading to non-inferiority of overall platelet function in cITP. Furthermore, we revealed that ADP-induced aggregation was impaired in the patients with thrombopoietin receptor agonists (TPO-RAs) or platelet-associated anti-αIIbβ3 antibodies compared with the control, suggesting that the presence of anti-αIIbβ3 autoantibodies and/or administration of TPO-RAs may have a negative impact on platelet function.

中文翻译:

重新评估慢性免疫性血小板减少症中的血小板功能:血小板大小,血小板相关抗αIIbβ3抗体和血小板生成素受体激动剂的影响。

免疫血小板减少症(ITP)的血小板功能一直存在争议,原因是与血小板计数低有关的方法学问题。在这项研究中,我们使用最近开发的基于流式细胞术(FCM)的血小板聚集测定(FCA)和PAC1 / CD62P测定,评估了21例慢性ITP(cITP)患者的血小板功能。由于ITP血小板要比对照大,因此通过FCM在PAC1 / CD62P中分析了整个血小板(全门控方法)和大小已调整的血小板(大小已调整方法)。我们发现:(i)与FCA对照相比,在cITP中聚集是等效的[佛波醇肉豆蔻酸酯乙酸酯(PMA)或腺苷二磷酸(ADP)诱导]或增强的[蛋白酶激活受体1激活肽(PAR1AP)诱导] ; (ii)在整个选通方法中,PAC1或CD62P在cITP中也相同或增强;(iii)与之形成鲜明对比的是,尺寸调整方法显示cITP中ADP-,PAR1AP-和胶原蛋白合成液体反应性肽(SRP)诱导的PAC1和ADP诱导的CD62P受损。这些数据表明,较大尺寸的血小板数量的增加可能弥补了cITP的血小板功能受损,从而导致cITP的整体血小板功能不逊色。此外,我们发现与血小板生成素受体激动剂(TPO-RAs)或血小板相关的抗αIIbβ3抗体相比,与对照组相比,ADP诱导的聚集受到损害,这表明抗αIIbβ3自身抗体的存在和/或给予TPO-RA可能会对血小板功能产生负面影响。胶原合成液体反应性肽(SRP)诱导的PAC1和ADP诱导的CD62P在cITP中受损。这些数据表明,较大尺寸的血小板数量的增加可能弥补了cITP的血小板功能受损,从而导致cITP的整体血小板功能不逊色。此外,我们发现与血小板生成素受体激动剂(TPO-RAs)或血小板相关的抗αIIbβ3抗体相比,与对照组相比,ADP诱导的聚集受到损害,这表明抗αIIbβ3自身抗体的存在和/或给予TPO-RA可能会对血小板功能产生负面影响。胶原合成液体反应性肽(SRP)诱导的PAC1和ADP诱导的CD62P在cITP中受损。这些数据表明,较大尺寸的血小板数量的增加可能弥补了cITP的血小板功能受损,从而导致cITP的整体血小板功能不逊色。此外,我们发现与血小板生成素受体激动剂(TPO-RAs)或血小板相关的抗αIIbβ3抗体相比,与对照组相比,ADP诱导的聚集受到损害,这表明抗αIIbβ3自身抗体的存在和/或给予TPO-RA可能会对血小板功能产生负面影响。导致cITP的整体血小板功能不逊色。此外,我们发现与血小板生成素受体激动剂(TPO-RAs)或血小板相关的抗αIIbβ3抗体相比,与对照组相比,ADP诱导的聚集受到损害,这表明抗αIIbβ3自身抗体的存在和/或给予TPO-RA可能会对血小板功能产生负面影响。导致cITP的整体血小板功能不逊色。此外,我们发现与血小板生成素受体激动剂(TPO-RAs)或血小板相关的抗αIIbβ3抗体相比,与对照组相比,ADP诱导的聚集受到损害,这表明抗αIIbβ3自身抗体的存在和/或给予TPO-RA可能会对血小板功能产生负面影响。
更新日期:2020-02-27
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