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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.

SUBMITTER: Ramirez-Lopez A

PROVIDER: S-EPMC8069668 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThrombocytopaenia is one of the most common haemostatic abnormalities among neonates. It affects approximately one-quarter of neonates admitted into neonatal intensive care units and may lead to a high risk of bleeding and mortality, which are substantial causes for concern by neonatologists. Platelet transfusion (PT) is a specific treatment for thrombocytopaenia. To date, PT thresholds are diverse since the associations between low platelet count and negative outcomes are not clear. We propose this protocol for a systematic review to collect and assess evidence concerning the best PT threshold to reduce mortality, bleeding and major morbidity among neonates with thrombocytopaenia.Methods and analysisThe systematic review will be performed according to the Cochrane Handbook for Systematic Review of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and the Grading of Recommendations Assessment, Development and Evaluation system. Two independent researchers will perform the study selection, data extraction/coding, quality assessment and further analyses of the included studies, with disagreements being resolved by a third researcher. A systematic search of the literature will be conducted in the PubMed, Cochrane Library and Embase databases from database inception through 13 October 2020. All randomised controlled trials, cohort studies and case-control studies will be included without any restrictions regarding publication date or language. The primary outcomes will comprise in-hospital mortality and bleeding episodes. Endnote X9 and Review Manager V.5.3 software will be used to manage the selection process and statistical analysis, respectively. If the included studies are sufficient and homogeneous for any of the outcomes, a quantitative synthesis (meta-analysis) may be performed. Otherwise, we will conduct a narrative systematic review of the results.Ethics and disseminationEthical approval is not required for this study because the data will be obtained from published studies and will not include individual patient data. The results of this study are anticipated to be published in a peer-reviewed journal.Prospero registration numberCRD42020169262.

Project description:Clostridium difficile infection (CDI) causes morbidity and mortality. Platelets have been increasingly recognized as an important component of innate and adaptive immunity. We aimed to assess the incidence of thrombocytopenia and thrombocytosis in CDI and the effect of an abnormal platelet count on clinical outcomes. This single-center, retrospective cohort study consisted of all adult patients hospitalized in Rabin Medical Center between 1 January 2013 and 31 December 2018 with laboratory confirmed CDI. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified by univariable and multivariable analyses, using logistic regression. A total of 527 patients with CDI were included. Among them 179 (34%) had an abnormal platelet count: 118 (22%) had thrombocytopenia and 61 (11.5%) had thrombocytosis. Patients with thrombocytosis were similar to control patients other than having a significantly higher white blood cell count at admission. Patients with thrombocytopenia were younger than control patients and were more likely to suffer from malignancies, immunosuppression, and hematological conditions. In a multivariable analysis, both thrombocytosis (OR 1.89, 95% CI 1.01-3.52) and thrombocytopenia (OR 1.70, 95% CI 1.01-2.89) were associated with 30-days mortality, as well as age, hypoalbuminemia, acute kidney injury, and dependency on activities of daily living. A sensitivity analysis restricted for patients without hematological malignancy or receiving chemotherapy revealed increased mortality with thrombocytosis but not with thrombocytopenia. In this retrospective study of hospitalized patients with CDI, we observed an association between thrombocytosis on admission and all-cause mortality, which might represent a marker for disease severity. Patients with CDI and thrombocytopenia also exhibited increased mortality, which might reflect their background conditions and not the severity of the CDI. Future studies should assess thrombocytosis as a severity marker with or without the inclusion of the WBC count.

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

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