Non-Anticoagulant Heparins as Heparanase Inhibitors

Cassinelli, Giuseppe; Torri, Giangiacomo; Naggi, Annamaria

doi:10.1007/978-3-030-34521-1_20

Cited by 34 publications

(41 citation statements)

References 155 publications

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“…Heparanase is a heparan sulfate degrading enzyme, which also has affinity for UFH. 45 Heparanase activity seems to be increased during inflammatory disease including sepsis-associated lung injury or bacterial and viral infection. 46 Evidence for increased heparanase expression in COVID-19 is lacking, but based on its ability to cleave UFH it could be involved in the ethology of heparin resistance in COVID-19 and may also be a potential target for further research.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2020

TH Open

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Objective Severe cases of coronavirus disease 2019 (COVID-19) can require continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO). Unfractionated heparin (UFH) to prevent circuit clotting is mandatory but monitoring is complicated by (pseudo)-heparin resistance. In this observational study, we compared two different activated partial thromboplastin time (aPTT) assays and a chromogenic anti-Xa assay in COVID-19 patients on CRRT or ECMO in relation to their UFH dosages and acute phase reactants. Materials and Methods The aPTT (optical [aPTT-CS] and/or mechanical [aPTT-STA] clot detection methods were used), anti-Xa, factor VIII (FVIII), antithrombin III (ATIII), and fibrinogen were measured in 342 samples from 7 COVID-19 patients on CRRT or ECMO during their UFH treatment. Dosage of UFH was primarily based on the aPTT-CS with a heparin therapeutic range (HTR) of 50-80s. Associations between different variables were made using linear regression and Bland-Altman analysis. Results Dosage of UFH was above 35,000IU/24 hours in all patients. aPTT-CS and aPTT-STA were predominantly within the HTR. Anti-Xa was predominantly above the Ã Equal contribution.

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Section: Discussionmentioning

confidence: 99%

Untitled

2020

TH Open

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“…135 However, the fine structure and pattern of distribution of sulphation sites along the chains essential for specific interactions of the heparins and heparinoids with the coagulation and immune systems have not been so precisely defined. Despite this, based on structural requirements, the relatively low content of 2-O, 3-O and 6-O-sulphated chains in danaparoid might promote heparanase inhibition, 116 but a direct study v UFH in a mouse cancer model did not confirm this. 136 However, the dose of heparin used in the latter study was 4 times that of danaparoid in terms of daily anti-Xa units administered, but it would have been more relevant to compare multiples of antithrombotic doses (for the mouse) since that is C-R ¼ cross reactivity with the platelet activating heparin:PF4 antibody, IIa ¼ thrombin.…”

Section: Heparins and Heparinoidsmentioning

confidence: 99%

Rationale for the Role of Heparin and Related GAG Antithrombotics in COVID-19 Infection

Magnani¹

2021

Clin Appl Thromb Hemost

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The SARS-CoV-2 pandemic has focused attention on prevention, restriction and treatment methods that are acceptable worldwide. This means that they should be simple and inexpensive. This review examines the possible role of glycosaminoglycan (GAG) antithrombotics in the treatment of COVID-19. The pathophysiology of this disease reveals a complex interplay between the hemostatic and immune systems that can be readily disrupted by SARS-CoV-2. Some of the GAG antithrombotics also possess immune-modulatory actions and since they are relatively inexpensive they could play an important role in the management of COVID-19 and its complications.

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“…The polysaccharide, a product of mast cells, is isolated from animal tissues (pig intestinal mucosa, bovine lung), and owes its anticoagulant activity to a specific pentasaccharide sequence ( Figure 1A properties. 10 We suggest that such products, that can be applied at higher dose, should be considered as a complement to conventional LMWH.…”

Section: Heparin -An Old Drug With Multiple Potential Targets In Covimentioning

confidence: 99%

Heparin – An old drug with multiple potential targets in Covid‐19 therapy

Lindahl

2020

Journal of Thrombosis and Haemostasis

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Non-Anticoagulant Heparins as Heparanase Inhibitors

Cited by 34 publications

References 155 publications

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Rationale for the Role of Heparin and Related GAG Antithrombotics in COVID-19 Infection

Heparin – An old drug with multiple potential targets in Covid‐19 therapy

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