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Recent Advances in Antithrombotic Agents

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 14616

Special Issue Editors


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Guest Editor
AP-HP Assistance Publique - Hopitaux de Paris, Paris, France and Inserm U1140 (head of the research unit "Innovative Therapies in Haemostasis")
Interests: haemostasis; thrombosis; platelets; antithrombotic drugs; vascular biology

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Guest Editor
Montreal Heart Institute, Montreal, QC, Canada
Interests: hemostasis; thrombosis; platelets; coagulation; antithrombotic drugs

Special Issue Information

Dear colleagues,

Antiplatelet agents and anticoagulants are the mainstay of treatment and prevention of thrombosis, which accounts for one in four deaths worldwide. Considerable advances in antithrombotic therapy have emerged during the last decade, especially with the commercialization of direct anti P2Y12 and oral anticoagulants (DOAC) as alternatives to standard therapies, respectively, aspirin/thienopyridines and vitamin-K antagonists/heparins.

Despite similar or better efficacy and safety profiles reported in large clinical trials, the side effect of bleeding remains a fundamental challenge with all antithrombotic drugs, resulting in a persistent major public-health concern. Furthermore, the number of patients suffering from recurrent thrombosis while under current therapy emphasizes the need for new compounds preventing thrombosis with less bleeding potential. These are eagerly awaited, considering the improved understanding of haemostasis and thrombosis mechanisms.

This Special Issue will focus on recent advances, current challenges, and future perspectives of antithrombotic therapy.

Dr. Pascale Gaussem
Dr. Georges Jourdi
Guest Editors

Manuscript Submission Information

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Keywords

  • Antiplatelets
  • Anticoagulants
  • Antithrombotics
  • Thrombosis
  • Bleeding.

Published Papers (3 papers)

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Review

19 pages, 406 KiB  
Review
Inherited Thrombophilia in the Era of Direct Oral Anticoagulants
by Lina Khider, Nicolas Gendron and Laetitia Mauge
Int. J. Mol. Sci. 2022, 23(3), 1821; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031821 - 05 Feb 2022
Cited by 17 | Viewed by 6726
Abstract
Severe inherited thrombophilia includes rare deficiencies of natural anticoagulants (antithrombin and proteins C and S) and homozygous or combined factor V Leiden and FII G20210A variants. They are associated with a high thrombosis risk and can impact the duration of anticoagulation therapy for [...] Read more.
Severe inherited thrombophilia includes rare deficiencies of natural anticoagulants (antithrombin and proteins C and S) and homozygous or combined factor V Leiden and FII G20210A variants. They are associated with a high thrombosis risk and can impact the duration of anticoagulation therapy for patients with a venous thromboembolism (VTE) event. Therefore, it is important to diagnose thrombophilia and to use adapted anticoagulant therapy. The widespread use of direct anticoagulants (DOACs) for VTE has raised new issues concerning inherited thrombophilia. Concerning inherited thrombophilia diagnosis, DOACs are directed toward either FIIa or FXa and can therefore interfere with coagulation assays. This paper reports DOAC interference in several thrombophilia tests, including the assessment of antithrombin, protein S, and protein C activities. Antithrombin activity and clot-based assays used for proteins C and S can be overestimated, with a risk of missing a deficiency. The use of a device to remove DOACs should be considered to minimize the risk of false-negative results. The place of DOACs in the treatment of VTE in thrombophilia patients is also discussed. Available data are encouraging, but given the variability in thrombosis risk within natural anticoagulant deficiencies, evidence in patients with well-characterized thrombophilia would be useful. Full article
(This article belongs to the Special Issue Recent Advances in Antithrombotic Agents)
15 pages, 886 KiB  
Review
Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome
by Julie Carré, Georges Jourdi, Nicolas Gendron, Dominique Helley, Pascale Gaussem and Luc Darnige
Int. J. Mol. Sci. 2022, 23(1), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010093 - 22 Dec 2021
Cited by 10 | Viewed by 3578
Abstract
For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting [...] Read more.
For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/− anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies. Full article
(This article belongs to the Special Issue Recent Advances in Antithrombotic Agents)
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25 pages, 1689 KiB  
Review
Current and Novel Antiplatelet Therapies for the Treatment of Cardiovascular Diseases
by Georges Jourdi, Marie Lordkipanidzé, Aurélien Philippe, Christilla Bachelot-Loza and Pascale Gaussem
Int. J. Mol. Sci. 2021, 22(23), 13079; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222313079 - 03 Dec 2021
Cited by 21 | Viewed by 3638
Abstract
Over the last decades, antiplatelet agents, mainly aspirin and P2Y12 receptor antagonists, have significantly reduced morbidity and mortality associated with arterial thrombosis. Their pharmacological characteristics, including pharmacokinetic/pharmacodynamics profiles, have been extensively studied, and a significant number of clinical trials assessing their efficacy [...] Read more.
Over the last decades, antiplatelet agents, mainly aspirin and P2Y12 receptor antagonists, have significantly reduced morbidity and mortality associated with arterial thrombosis. Their pharmacological characteristics, including pharmacokinetic/pharmacodynamics profiles, have been extensively studied, and a significant number of clinical trials assessing their efficacy and safety in various clinical settings have established antithrombotic efficacy. Notwithstanding, antiplatelet agents carry an inherent risk of bleeding. Given that bleeding is associated with adverse cardiovascular outcomes and mortality, there is an unmet clinical need to develop novel antiplatelet therapies that inhibit thrombosis while maintaining hemostasis. In this review, we present the currently available antiplatelet agents, with a particular focus on their targets, pharmacological characteristics, and patterns of use. We will further discuss the novel antiplatelet therapies in the pipeline, with the goal of improved clinical outcomes among patients with atherothrombotic diseases. Full article
(This article belongs to the Special Issue Recent Advances in Antithrombotic Agents)
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