Abstract Number: PB1333
Meeting: ISTH 2020 Congress
Background: One way platelets are cleared in immune thrombocytopenia (ITP) is by desialylation of glycans. We hypothesize that loss of sialic acid might also modify platelet function in ITP patients.
Aims: So we aimed to evaluate the pattern of platelet glycosylation in ITP patients and its involvement in platelet function to contribute to the growing body of knowledge about platelet glycosylation and its role in ITP.
Methods: This was an observational, prospective and transversal study approved by La Paz University Hospital Ethics Committee. Forty two patients with chronic primary ITP and forty eight healthy controls were included after signing the informed consent.
Platelet activation markers in platelet rich plasma and platelet glycosylation in washed platelets were determined by flow cytometry. Table 1 shows lectins tested and their sugar-binding specificity.
Data were analyzed with GraphPad Prism 5.0 software.
Results: Platelets from ITP patients were basally activated, as shown by the exposure of P-selectin and CD63 on their surface, but their response to agonist activation (100 µM TRAP and 10 µM ADP) was reduced (Figure 1A).
Platelets from ITP patients exposed less sialic acid in correspondence to an enhanced binding of lectins to non-sialylated residues (Figure 1B). Levels of α1,6-Fucose, a glycan residue which could directly regulate antibody-dependent cellular cytotoxicity, and of α-Mannose, which could be recognized by the mannose binding lectin and activate complement pathway, were increased in platelets from ITP patients. In accordance, sialic acid loss and consequent platelet surface exposure of other glycan residues were inversely related to platelet count and ability to be activated (Table 1).
|Lectins tested||Abbr.||Sugar specificity||Lectin binding vs Platelet count (Spearman Rho; p)||Lectin binding vs TRAP-induced PAC1 binding (Spearman Rho; p)|
|Aleuria aurantia||AA||α1,6-Fucose||-0.3946; 0.0002||-0.2297; 0.0392|
|Concanavalin A||CA||α-Mannose||-0.3964; 0.0002||-0.2567; 0.0191|
|Dolichos biflorus agglutinin||DB||GalNAcα1-3GalNAc||-0.6110; <0.0001||-0.4172; <0.0001|
|Datura stramonium||DS||GlcNAc||-0.4091; 0.0001||-0.2581; 0.0185|
|Ricinus communis agglutinin||RCA||β-Gal||-0.3707; 0.026||-0.298; 0.0160|
|Wheat Germ Agglutinin||WGA||β-GlcNac||-0.2868; 0.0177||-0.3737; 0.0007|
Conclusions: Surface of platelets from ITP patients suffered changes in their carbohydrate composition due to the loss of sialic acid that might induce platelet clearence/destruction through several mechanisms.
This work was supported by grants from FIS-FONDOS FEDER (PI19/00772) and Platelet Disorder Support Association.
To cite this abstract in AMA style:Monzon Manzano E, Acuña P, Álvarez Román MT, Martín Salces M, Rivas Pollmar MI, Fernández Bello I, Jiménez Yuste V, Butta N. Relationship between Platelet Function and Glycome Composition in Immune Thrombocytopenia [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/relationship-between-platelet-function-and-glycome-composition-in-immune-thrombocytopenia/. Accessed October 1, 2023.
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