Schramm Theresa, Zlamal Jan, Rast Jasmin, Oosterlee Justin, Fillitz Michael, Mehic Dino, Kraemmer Daniel, Tolios Alexander, Haslacher Helmut, Ay Cihan, Pabinger Ingrid, Althaus Karina, Bakchoul Tamam, Gebhart Johanna
Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Institute for Clinical and Experimental Transfusion Medicine, University Hospital of Tübingen, Tübingen, Germany; Centre for Clinical Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany.
J Thromb Haemost. 2025 Sep;23(9):2958-2968. doi: 10.1016/j.jtha.2025.05.024. Epub 2025 Jun 3.
Autoantibody (AAb)-induced platelet desialylation, resulting in increased hepatic platelet clearance, has previously been reported as pathomechanism in immune thrombocytopenia (ITP).
To elucidate platelet desialylation capacity and its impact on clinical outcomes in adult primary ITP patients from the Vienna ITP biobank (EC 1843/2016).
Desialylation was assessed using a lectin-binding assay which evaluated the exposure of β-galactose and N-acetylglucosamine on platelets.
Sera from 133 ITP patients (28% newly diagnosed and 72% persistent/chronic) were investigated, where sera of 38 patients (29%) induced platelet desialylation. Patients with desialylation capacity compared with those without more commonly had platelet-bound AAbs (n = 19/46, 50% vs n = 27/95, 28.4%; P = .018), thrombopoietin levels > 50 pg/mL (n = 23/34, 67.6% vs n = 37/38, 42.0%; P = .011), and higher bleeding scores (median [IQR], 3.0 [1.0-5.0] vs 1.0 [0.0-4.0]; P = .043). While the bleeding score overall, specifically the skin bleeding score, thrombopoietin > 50 pg/mL, and the presence of AAbs showed a significant association in univariate analysis with desialylating AAbs, only positivity for antiplatelet AAbs remained significantly associated in multivariate binary logistic regression analysis. In contrast, no association was seen between platelet desialylation capacity and disease duration, ITP treatment, or previous splenectomy.
Platelet desialylation capacity was seen in a third of primary ITP patients and was associated with platelet-bound antiglycoprotein IIbIIIa AAbs, although more studies are required to establish the linkage with antiglycoprotein Ib-IX AAbs. Desialylation capacity was associated with a more severe bleeding phenotype, while, in contrast to previous data, an association with platelet counts, disease duration, ITP treatment, and splenectomy refractoriness was not confirmed.
自身抗体（AAb）诱导的血小板去唾液酸化，导致肝脏对血小板的清除增加，此前已被报道为免疫性血小板减少症（ITP）的发病机制。
阐明来自维也纳ITP生物样本库（EC 1843/2016）的成年原发性ITP患者的血小板去唾液酸化能力及其对临床结局的影响。
使用凝集素结合试验评估去唾液酸化，该试验评估血小板上β-半乳糖和N-乙酰葡糖胺的暴露情况。
研究了133例ITP患者的血清（28%为新诊断患者，72%为持续性/慢性患者），其中38例患者（29%）的血清诱导了血小板去唾液酸化。与无去唾液酸化能力的患者相比，有去唾液酸化能力的患者更常见血小板结合型AAb（n = 19/46，50%对n = 27/95，28.4%；P = 0.018）、血小板生成素水平>50 pg/mL（n = 23/34，67.6%对n = 37/38，42.0%；P = 0.011）以及更高的出血评分（中位数[四分位间距]，3.0[1.0 - 5.0]对1.0[0.0 - 4.0]；P = （0.043）。虽然总体出血评分，特别是皮肤出血评分、血小板生成素>50 pg/mL以及AAb的存在在单因素分析中与去唾液酸化AAb有显著关联，但在多因素二元逻辑回归分析中，仅抗血小板AAb阳性仍有显著关联。相比之下，未观察到血小板去唾液酸化能力与疾病持续时间、ITP治疗或既往脾切除术之间存在关联。
三分之一的原发性ITP患者存在血小板去唾液酸化能力，且与血小板结合的抗糖蛋白IIbIIIa AAb有关，不过需要更多研究来确定与抗糖蛋白Ib - IX AAb的联系。去唾液酸化能力与更严重的出血表型相关，而与之前的数据相反，未证实与血小板计数、疾病持续时间、ITP治疗及脾切除难治性存在关联。
