Observational studyPLoS pathogens2019
Desialylation of platelets induced by Von Willebrand Factor is a novel mechanism of platelet clearance in dengue.
Observational study in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Effect of oseltamivir phosphate versus placebo on platelet recovery and plasma leakage in adults with dengue and thrombocytopenia; a phase 2, multicenter, double-blind, randomized trial.PLoS neglected tropical diseases · 2022Trial
- Clinical application of a modified platelet desialylation test for mechanistic characterization of platelet transfusion refractoriness.Transfusion · 2026Article
- The glycan fingerprint in immune thrombocytopenia.Research and practice in thrombosis and haemostasis · 2026Article
- Stratified assessment of platelets in sepsis: from dynamic counts to functional phenotypes.Frontiers in immunology · 2026Review
- Pilot proteomic analysis of immune dysregulation in dengue with prior SARS-CoV-2 infection.Frontiers in immunology · 2025Observational
- Thrombocytopenia in dengue infection: mechanisms and a potential application.Expert reviews in molecular medicine · 2024Review
- Immuno-Haematologic Aspects of Dengue Infection: Biologic Insights and Clinical Implications.Viruses · 2024Review
- Increased von Willebrand Factor Platelet-Binding Capacity Is Related to Poor Prognosis in COVID-19 Patients.Thrombosis and haemostasis · 2023Article
- Platelets interact with CD169Frontiers in immunology · 2023Article
- Dengue: Update on Clinically Relevant Therapeutic Strategies and Vaccines.Current treatment options in infectious diseases · 2023Review
- Molecular Determinants of Tissue Specificity of Flavivirus Nonstructural Protein 1 Interaction with Endothelial Cells.Journal of virology · 2022Article
- Viral-Induced Inflammatory Coagulation Disorders: Preparing for Another Epidemic.Thrombosis and haemostasis · 2022Review
- Viral Dynamic Surveillance in COVID-19 Patients: A Cohort Study.BioMed research international · 2022Article
- Platelets in Viral Infections - Brave Soldiers or Trojan Horses.Frontiers in immunology · 2022Review
- Review
- Efficiently Restored Thrombopoietin Production by Ashwell-Morell Receptor and IL-6R Induced Janus Kinase 2/Signal Transducer and Activator of Transcription Signaling Early After Partial Hepatectomy.Hepatology (Baltimore, Md.) · 2021Article
- Von Willebrand factor with increased binding capacity is associated with reduced platelet aggregation but enhanced agglutination in COVID-19 patients: another COVID-19 paradox?Journal of thrombosis and thrombolysis · 2021Article
- Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis.Cell reports. Medicine · 2021Article
- The Importance of Platelet Glycoside Residues in the Haemostasis of Patients with Immune Thrombocytopaenia.Journal of clinical medicine · 2021Article
- Dissecting pathways to thrombocytopenia in a mouse model of visceral leishmaniasis.Blood advances · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombocytopenia and platelet dysfunction are commonly observed in patients with dengue virus (DENV) infection and may contribute to complications such as bleeding and plasma leakage. The etiology of dengue-associated thrombocytopenia is multifactorial and includes increased platelet clearance. The binding of the coagulation protein von Willebrand factor (VWF) to the platelet membrane and removal of sialic acid (desialylation) are two well-known mechanisms of platelet clearance, but whether these conditions also contribute to thrombocytopenia in dengue infection is unknown. In two observational cohort studies in Bandung and Jepara, Indonesia, we show that adult patients with dengue not only had higher plasma concentrations of plasma VWF antigen and active VWF, but that circulating platelets had also bound more VWF to their membrane. The amount of platelet-VWF binding correlated well with platelet count. Furthermore, sialic acid levels in dengue patients were significantly reduced as assessed by the binding of Sambucus nigra lectin (SNA) and Maackia amurensis lectin II (MAL-II) to platelets. Sialic acid on the platelet membrane is neuraminidase-labile, but dengue virus has no known neuraminidase activity. Indeed, no detectable activity of neuraminidase was present in plasma of dengue patients and no desialylation was found of plasma transferrin. Platelet sialylation was also not altered by in vitro exposure of platelets to DENV nonstructural protein 1 or cultured DENV. In contrast, induction of binding of VWF to glycoprotein 1b on platelets using the VWF-activating protein ristocetin resulted in the removal of platelet sialic acid by translocation of platelet neuraminidase to the platelet surface. The neuraminidase inhibitor oseltamivir reduced VWF-induced platelet desialylation. Our data demonstrate that excessive binding of VWF to platelets in dengue results in neuraminidase-mediated platelet desialylation and platelet clearance. Oseltamivir might be a novel treatment option for severe thrombocytopenia in dengue infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.