Multifaceted role of glycosylation in transfusion medicine, platelets, and red blood cells

Lee‐Sundlov, Melissa M.; Stowell, Sean R.; Hoffmeister, Karin M.

doi:10.1111/jth.14874

Cited by 36 publications

(29 citation statements)

References 126 publications

(255 reference statements)

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“…For instance, regarding the apoptosis-related Bcl/Bax proteins (C 18 ) involved in platelet clearance 49 , the isoforms BNIP2, BCL2L1 (BCL-XL or BIM), BAD and BAK1 are present in the current proteome, while also the transcripts of BLC7B, BCL9 and BCL2 are highly expressed. As another example, regarding the glycosyl transferases (C 16 ) and epimerases (C 12 ) implicated in the surface glycosylation pattern and thereby in platelet survival time 50 , prominently present in the proteome (transcriptome) are GALM, GALE, GNE, C1GALT1 and B4GALT1/3/4/5/6, while C1GALT1C1 (COSMC) is only lowly transcribed.…”

Section: Discussionmentioning

confidence: 99%

Assessment of a complete and classified platelet proteome from genome-wide transcripts of human platelets and megakaryocytes covering platelet functions

Huang

Swieringa

Solari

et al. 2021

Sci Rep

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Novel platelet and megakaryocyte transcriptome analysis allows prediction of the full or theoretical proteome of a representative human platelet. Here, we integrated the established platelet proteomes from six cohorts of healthy subjects, encompassing 5.2 k proteins, with two novel genome-wide transcriptomes (57.8 k mRNAs). For 14.8 k protein-coding transcripts, we assigned the proteins to 21 UniProt-based classes, based on their preferential intracellular localization and presumed function. This classified transcriptome-proteome profile of platelets revealed: (i) Absence of 37.2 k genome-wide transcripts. (ii) High quantitative similarity of platelet and megakaryocyte transcriptomes (R = 0.75) for 14.8 k protein-coding genes, but not for 3.8 k RNA genes or 1.9 k pseudogenes (R = 0.43–0.54), suggesting redistribution of mRNAs upon platelet shedding from megakaryocytes. (iii) Copy numbers of 3.5 k proteins that were restricted in size by the corresponding transcript levels (iv) Near complete coverage of identified proteins in the relevant transcriptome (log2fpkm > 0.20) except for plasma-derived secretory proteins, pointing to adhesion and uptake of such proteins. (v) Underrepresentation in the identified proteome of nuclear-related, membrane and signaling proteins, as well proteins with low-level transcripts. We then constructed a prediction model, based on protein function, transcript level and (peri)nuclear localization, and calculated the achievable proteome at ~ 10 k proteins. Model validation identified 1.0 k additional proteins in the predicted classes. Network and database analysis revealed the presence of 2.4 k proteins with a possible role in thrombosis and hemostasis, and 138 proteins linked to platelet-related disorders. This genome-wide platelet transcriptome and (non)identified proteome database thus provides a scaffold for discovering the roles of unknown platelet proteins in health and disease.

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Section: Discussionmentioning

confidence: 99%

Assessment of a complete and classified platelet proteome from genome-wide transcripts of human platelets and megakaryocytes covering platelet functions

Huang

Swieringa

Solari

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…This study also confirmed the higher risk in blood group A than in other blood groups (odds ratio [OR] 1.45; 95% CI 1.20–1.75) and a protective effect in blood group O versus the other blood groups (OR 0.65; 95% CI 0.53–0.79) [74]. These findings could be due to elevated vWF levels in non-group O individuals, which predispose to thromboembolic events, as has been well-described prior to the current pandemic [75].…”

Section: Endothelium Von Willebrand Factor and Abo Blood Groupmentioning

confidence: 99%

The Impact of COVID-19 Disease on Platelets and Coagulation

2020

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Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. Initially, COVID-19 infection produces a prominent elevation of fibrinogen and D-dimer/fibrin(ogen) degradation products. This is associated with systemic hypercoagulability and frequent venous thromboembolic events. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients. COVID-19 also leads to arterial thrombotic events (including strokes and ischemic limbs) as well as microvascular thrombotic disorders (as frequently documented at autopsy in the pulmonary vascular beds). COVID-19 patients often have mild thrombocytopenia and appear to have increased platelet consumption, together with a corresponding increase in platelet production. Disseminated intravascular coagulopathy (DIC) and severe bleeding events are uncommon in COVID-19 patients. Here, we review the current state of knowledge of COVID-19 and hemostasis.

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“…Supporting the importance of sialyl transferases in the platelets’ lifespan, mice lacking ST3GAL4 (an enzyme that transfers sialic acid onto β1,4-galactose) develop thrombocytopaenia due to increased platelet clearance via the hepatic Ashwell–Morell receptor [ 32 ]. Moreover, the lack of ST3GAL1 (an enzyme that caps the Thomsen–Friedenreich antigen with sialic acid) was associated with platelet counts 50% lower than normal, as observed in ST3GAL1-null mice [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 98%

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

Ramírez-López

Roman

Manzano

et al. 2021

JCM

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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.

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Multifaceted role of glycosylation in transfusion medicine, platelets, and red blood cells

Cited by 36 publications

References 126 publications

Assessment of a complete and classified platelet proteome from genome-wide transcripts of human platelets and megakaryocytes covering platelet functions

Assessment of a complete and classified platelet proteome from genome-wide transcripts of human platelets and megakaryocytes covering platelet functions

The Impact of COVID-19 Disease on Platelets and Coagulation

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

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