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 January 28, 2022.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-desialylation-affects-bleeding-tendency-in-immune-thrombocytopenic-patients/