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Platelet Desialylation Affects Bleeding Tendency in Immune Thrombocytopenic Patients

I. Marini1, J. Zlamal1, L. Pelzl1, K. Althaus1,2, T. Bakchoul1,2

1University of Tubingen, Medical Faculty of Tübingen, Tübingen, Germany, 2Centre for Clinical Transfusion Medicine, Tübingen, Germany

Abstract Number: OC 13.5

Meeting: ISTH 2020 Congress

Theme: Platelet Disorders and von Willebrand Disease » Inherited Thrombocytopenias

Background: Immune thrombocytopenia (ITP) is a bleeding disorder caused by autoantibodies (AAbs) against platelet´s (PLT) glycoproteins. Desialylation, the loss of sialic acid from PLT glycoproteins, has been reported to contribute to the increased PLT destruction and reduced PLT formation (Haematologica PMID: 31857361).

Aims: To assess the impact of desialylating AAbs on the bleeding tendency/manifestations of ITP patients.

Methods: The desialylation ability of 100 well-characterized ITP patients was analysed by flow cytometry. Platelet count, bleeding tendency and platelet adhesion were investigated.

Results: The median PLT count of the study cohort was 32×109/L (interquartile range [IQR]: 7-74×109/L). Interestingly, a lower PLT count was found in patients with desialylating ITP-AAbs compared to patients with non-desialylating AAbs (median and IQR: 13×109/L IQR 5-42×109/L vs. 46×109/L IQR 11-81×109/L, p=0.0286). Moreover, the bleeding events were reported in 48/100 patients and the potential impact of PLT desialylation on the bleeding manifestations was investigated. Interestingly, bleeding symptoms were often observed in patients with desialylating AAbs (% patients with bleeding: desialylating vs. non-desialylating ITP-AAbs, 72% vs. 28%, p=0.0008). Particularly, higher tendency to develop petechiae (46% vs. 19%, p value 0.0044) and hematoma (49% vs. 17%, p value 0.0009) was observed in patients with desialylating AAbs compared to non-desialylating once. To explore the mechanism underlying this effect we analyzed the platelet function. Impaired adhesion to fibrinogen and vWF was observed in the presence of desialylating ITP-AAbs which was significantly improved by the pretreatment with a sialidase inhibitor (% adherent PLTs/field mean±SEM desialylating ITP-AAbs without vs. with sialidase: 36±5% vs. 86±56%, p=0.0001 and 26±2% vs. 67±11%, p=0.02, respectively).

Conclusions: Our findings demonstrate a correlation between ITP patients with desialylating AAbs and their reduced PLT count and bleeding tendency. This suggests a potential clinical relevance of PLT´s desialylation as target for diagnostic tools and therapeutic approaches in the treatment of ITP.

To cite this abstract in AMA style:

Marini I, Zlamal J, Pelzl L, Althaus K, Bakchoul T. Platelet Desialylation Affects Bleeding Tendency in Immune Thrombocytopenic Patients [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/platelet-desialylation-affects-bleeding-tendency-in-immune-thrombocytopenic-patients/. Accessed September 22, 2023.

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