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

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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.

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