The Importance of Platelet Glycoside Residues in the Haemostasis of Patients with Immune Thrombocytopaenia

Abstract

Loss of sialic acid from the carbohydrate side chains of platelet glycoproteins can affect platelet clearance, a proposed mechanism involved in the etiopathogenesis of immune thrombocytopaenia (ITP). We aimed to assess whether changes in platelet glycosylation in patients with ITP affected platelet counts, function, and apoptosis. This observational, prospective, and transversal study included 82 patients with chronic primary ITP and 115 healthy controls. We measured platelet activation markers and assayed platelet glycosylation and caspase activity, analysing samples using flow cytometry. Platelets from patients with ITP with a platelet count <30 × 103/µL presented less sialic acid. Levels of α1,6-fucose (a glycan residue that can directly regulate antibody-dependent cellular cytotoxicity) and α-mannose (which can be recognised by mannose-binding-lectin and activate the complement pathway) were increased in the platelets from these patients. Platelet surface exposure of other glycoside residues due to sialic acid loss inversely correlated with platelet count and the ability to be activated. Moreover, loss of sialic acid induced the ingestion of platelets by human hepatome HepG2 cells. Changes in glycoside composition of glycoproteins on the platelets’ surface impaired their functional capacity and increased their apoptosis. These changes in platelet glycoside residues appeared to be related to ITP severity.

Association of Platelet Desialylation and Circulating Follicular Helper T Cells in Patients With Thrombocytopenia

“…They showed that megakaryopoiesis, platelet apoptosis and platelet desialylation did not follow a specific pattern in ITP patients. A recent study showed that changes in glycoside composition of glycoproteins on the platelets’ surface impaired the functional capacity of platelets and increased their apoptosis, which may be related to ITP severity ( 55 ). Our data showed that half of the samples (50%) exhibited both abnormalities; 24% and 16% of these samples presented only increased apoptosis or desialylation, respectively; while 10% of them behaved normally.…”

A bibliometric analysis of primary immune thrombocytopenia from 2011 to 2021

“…35 Apart from the importance of sialic acid in the platelet clearance, 117 more researchers also found that sialic acid played an important role in the production, functional capacity, and apoptosis of platelets. 118,119 At the same time, non-responders to the first-line therapies had significantly higher levels of platelet desialylation. 120 More studies are needed to further establish the importance of platelet desialylation in ITP.…”

New insights into the glycobiology of immune thrombocytopenia

“…RCA-I and ECL preferentially bind to glycans terminating in Gal or GalNAc, the monosaccharides expected to be exposed following cleavage of Sia. In several flow cytometry studies, ITP platelets were shown to have increased binding to RCA-I and/or ECL compared with healthy platelets, suggesting desialylation of platelet glycans [27–31].…”