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. 2025 Sep;23(9):2958-2968.
doi: 10.1016/j.jtha.2025.05.024. Epub 2025 Jun 3.

Clinical evidence for antiglycoprotein IIbIIIa antibody-induced platelet desialylation in primary immune thrombocytopenia

Theresa Schramm  1 , Jan Zlamal  2 , Jasmin Rast  1 , Justin Oosterlee  1 , Michael Fillitz  3 , Dino Mehic  1 , Daniel Kraemmer  1 , Alexander Tolios  4 , Helmut Haslacher  5 , Cihan Ay  1 , Ingrid Pabinger  1 , Karina Althaus  2 , Tamam Bakchoul  2 , Johanna Gebhart  6
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Free article

Clinical evidence for antiglycoprotein IIbIIIa antibody-induced platelet desialylation in primary immune thrombocytopenia

Theresa Schramm et al. J Thromb Haemost. 2025 Sep.
Free article

Abstract

Background: Autoantibody (AAb)-induced platelet desialylation, resulting in increased hepatic platelet clearance, has previously been reported as pathomechanism in immune thrombocytopenia (ITP).

Objectives: To elucidate platelet desialylation capacity and its impact on clinical outcomes in adult primary ITP patients from the Vienna ITP biobank (EC 1843/2016).

Methods: Desialylation was assessed using a lectin-binding assay which evaluated the exposure of β-galactose and N-acetylglucosamine on platelets.

Results: 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.

Conclusion: 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.

Keywords: GPIIbIIIa; desialylation; immune thrombocytopenia; lectin binding.

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Conflict of interest statement

Declaration of competing interests J.Z. is supported by grants from the Blood Service of the German Red Cross and takes part in the MINT-Clinician Scientist Program (CS 3015-0-0) of the Medical Faculty Tübingen, funded by Deutsche Forschungsgemeinschaft (493665037). D.M. received honoraria for advisory board meetings and lectures from CSL Behring and travel support from Sobi, Novo Nordisk, Pfizer, and Roche. C.A. received personal fees for lectures and/or participation in advisory boards from Amgen, Novartis, and Sobi. I.P. has received honoraria from Bayer, CSL Behring, Novo Nordisk, Pfizer, Roche, Sobi, and Takeda for lectures and advisory board meetings. K.A. received honoraria for lectures and research funding from the Medical University of Tuebingen, CSL Behring, Sobi, Biotest, Meet The Experts, Expanda, Octapharma, and Bayer. T.B. has received research funding from CoaChrom Diagnostica GmbH, Deutsche Forschungsgemeinschaft, Robert Bosch GmbH, Stiftung Transfusionsmedizin und Immunhämatologie e.V.: Ergomed, DRK Blutspendedienst, Deutsche Herzstiftung, Ministerium fuer Wissenschaft, and Forschung und Kunst Baden–Wuerttemberg; has received lecture honoraria from Aspen Germany GmbH, Bayer Vital GmbH, Bristol–Myers Squibb GmbH and Co, Doctrina Med AG, Meet The Experts Academy UG, Schoechl Medical Education GmbH, Stago GmbH, Mitsubishi Tanabe Pharma GmbH, Novo Nordisk Pharma GmbH, Leo Pharma GmbH, and Swedish Orphan Biovitrum GmbH; has provided consulting services to Terumo; and has provided expert witness testimony relating to heparin-induced thrombocytopenia (HIT) and non-HIT thrombocytopenic and coagulopathic disorders. J.G. received honoraria for lectures and advisory board meetings and research funding from the Medical University of Vienna, CSL Behring, Novartis, Amgen, Takeda, and Sobi. T.S., J.R., J.O., M.F., D.K., A.T., and H.H. have no conflicts of interest.

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