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      When Will Fondaparinux Induce Thrombocytopenia?

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          Abstract

          The pentasaccharide Fondaparinux, a synthetic selective factor Xa inhibitor, is one of the safest anticoagulants in the heparin family that is recommended as an alternative drug for patients with hypersensitivity to other drugs such as heparin-induced thrombocytopenia (HIT). However, some observations of Fondaparinux-induced thrombocytopenia (FIT) have been reported while others claimed that FIT does not occur in patients with fondaparinux therapy, indicating that the mechanism of FIT remains controversial. Here, we utilized different methodologies including dynamic light scattering, immunosorbent and platelet aggregation assays, confocal laser scanning microscopy, and flow cytometry to gain insights into FIT. We found that at a certain concentration, Fondaparinux formed sufficient large and stable complexes with PF4 that facilitated binding of the HIT-like monoclonal KKO antibody and enhanced platelet aggregation and activation. We proposed a model to describe the role of Fondaparinux concentration in the formation of complexes with platelet factor 4 and how it promotes the binding of KKO. Our results clarify controversial observations of FIT in patients as each contains a dissimilar PF4:Fondaparinux concentration ratio.

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          Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

          Background A relatively high mortality of severe coronavirus disease 2019 (COVID‐19) is worrying, and the application of heparin in COVID‐19 has been recommended by some expert consensus because of the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated. Methods Coagulation results, medications, and outcomes of consecutive patients being classified as having severe COVID‐19 in Tongji hospital were retrospectively analyzed. The 28‐day mortality between heparin users and nonusers were compared, as was a different risk of coagulopathy, which was stratified by the sepsis‐induced coagulopathy (SIC) score or D‐dimer result. Results There were 449 patients with severe COVID‐19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin) for 7 days or longer. D‐dimer, prothrombin time, and age were positively, and platelet count was negatively, correlated with 28‐day mortality in multivariate analysis. No difference in 28‐day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P  = .910). But the 28‐day mortality of heparin users was lower than nonusers in patients with SIC score ≥4 (40.0% vs 64.2%, P  = .029), or D‐dimer >6‐fold of upper limit of normal (32.8% vs 52.4%, P  = .017). Conclusions Anticoagulant therapy mainly with low molecular weight heparin appears to be associated with better prognosis in severe COVID‐19 patients meeting SIC criteria or with markedly elevated D‐dimer.
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            Platelets Can Associate With SARS-CoV-2 RNA and Are Hyperactivated in COVID-19

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              Heparin-Protein Interactions

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                Author and article information

                Journal
                Bioconjug Chem
                Bioconjug Chem
                bc
                bcches
                Bioconjugate Chemistry
                American Chemical Society
                1043-1802
                1520-4812
                25 July 2022
                17 August 2022
                25 July 2023
                : 33
                : 8
                : 1574-1583
                Affiliations
                []Institute for Bioprocessing and Analytical Measurement Techniques , 37308 Heiligenstadt, Germany
                []Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology , 07745 Jena, Germany
                [§ ]Faculty of Mathematics and Natural Sciences, Technische Universität Ilmenau , 98694 Ilmenau, Germany
                Author notes
                Author information
                https://orcid.org/0000-0002-9237-3482
                Article
                10.1021/acs.bioconjchem.2c00316
                9390334
                35878320
                c3a5f950-db18-45de-b65a-8deb5b77fc1f
                © 2022 The Authors. Published by American Chemical Society

                Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 03 July 2022
                : 12 July 2022
                Funding
                Funded by: Deutsche Forschungsgemeinschaft, doi 10.13039/501100001659;
                Award ID: 469240103 and 269095734
                Funded by: Thüringer Ministerium für Wirtschaft, Wissenschaft und Digitale Gesellschaft, doi 10.13039/501100010959;
                Award ID: NA
                Categories
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                Custom metadata
                bc2c00316
                bc2c00316

                Biochemistry
                Biochemistry

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