Novel approaches to antiplatelet therapy

Gresele, Paolo; Momi, Stefania

doi:10.1016/j.bcp.2022.115297

Cited by 7 publications

(7 citation statements)

References 210 publications

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“…Until now, there is no recommendation for the use of antiplatelet therapy in patients with liver disease since its use requires careful monitoring due to possible bleeding complications, especially in patients with cirrhosis. Here, further studies with more specific antiplatelet agents, like GPVI, PAR4, or PI3K inhibitors may reduce possible bleeding complications ( 301 ). Platelets can influence macrophage differentiation and polarization through direct cell-cell interaction and the release of growth factors, cytokines, chemokines, and other mediators, affecting their pro-inflammatory, anti-tumor, and profibrotic phenotype, offering platelet-targeted treatment approaches ( 288 ).…”

Section: Discussionmentioning

confidence: 99%

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Casari,

Siegl,

Deppermann

et al. 2023

Front. Immunol.

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During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Casari,

Siegl,

Deppermann

et al. 2023

Front. Immunol.

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“…Therefore, heparin has a strong anticoagulant effect mainly through the combination of sulfate and carboxylic acid groups with proteins. , Apart from unfractionated heparin, low molecular weight heparin (LMWH) has become an anticoagulant choice in many clinical applications, including the management of venous thromboembolism (VTE), major surgery, and acute coronary syndrome . In the treatment of arterial thrombotic diseases, such as coronary heart disease and cerebral thrombosis, in addition to adjuvant therapy by oral or injection of antithrombotic drugs , (aspirin, clopidogrel, and cilostazol, etc. ), the risk of thrombosis can also be reduced by inhibiting platelet aggregation.…”

Section: Anticoagulant Mechanism Molecular Characteristics and Classi...mentioning

confidence: 99%

Anticoagulant Macromolecules

et al. 2023

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Anticoagulant macromolecules have gained widespread use in the clinical treatment of cardiovascular diseases, blood-contacting or implantable materials, and medical devices due to their excellent anticoagulant properties. Inspired by the molecular characteristics of physiological anticoagulants that play a vital role in normal human coagulation and anticoagulation mechanisms, diverse anticoagulant macromolecules with special molecular structures and functional groups have been developed, where they can be systematically applied to the biomedical field. In this Perspective, the history and the recent progress of synthetic methods for anticoagulant macromolecules obtained by purification of natural products, semisynthetic methods, and synthetic methods are discussed from the aspect of molecular design. The critical application and immense development potential of these anticoagulant macromolecules in the field of clinical treatment and biomedicine is proposed.

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“…Similarly, platelet activation and aggregation are associated with inflammatory conditions, and platelet depletion with the development of disseminated intravascular coagulopathy, in conditions such as sepsis ( 3 ). Antiplatelet drugs are intended to prevent or limit platelet activation and aggregation and are generally used in acute coronary syndrome (ACS) and ischemic stroke patients for long-term control or secondary prevention ( 4 – 7 ). As the same mechanistic processes are responsible for both physiological and pathological platelet aggregation, striking a balance between the beneficial and harmful effects of antiplatelet therapy continues to be a challenge.…”

Section: The Present and Future Of Antiplatelet Therapeuticsmentioning

confidence: 99%

“…Other current antiplatelet therapy ( Figure 1 ) includes phosphodiesterase (PDE) inhibitors (cilostazol, dipyridamole), αIIbβ3 antagonists (abciximab, eptifibatide, and tirofiban), and protease-activated receptor-1 (PAR1) antagonists (vorapaxar) ( 4 – 7 ). PDE inhibitors reduce platelet reactivity by increasing the cyclic nucleotides cAMP and/or cGMP, thereby dampening cytoskeletal rearrangement, integrin αIIbβ3 activation, and platelet secretion by interfering with activation signaling pathways ( 21 ).…”

Section: The Present and Future Of Antiplatelet Therapeuticsmentioning

confidence: 99%

“…Overall, antiplatelet therapy is still associated with non-negligible to high bleeding risk and thrombocytopenia, a meaningful variability in individual response due to genetic factors, and generally poor biological response in patients with comorbidities, such as diabetes and obesity ( 4 – 7 , 18 ). In the next section, pharmacological approaches to platelet inhibition currently being considered, under development, or undergoing clinical testing, will be reviewed.…”

Section: The Present and Future Of Antiplatelet Therapeuticsmentioning

confidence: 99%

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Novel strategies in antithrombotic therapy: targeting thrombosis while preserving hemostasis

Sim,

Shiferawe,

Wood

2023

Front. Cardiovasc. Med.

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Antithrombotic therapy is a delicate balance between the benefits of preventing a thrombotic event and the risks of inducing a major bleed. Traditional approaches have included antiplatelet and anticoagulant medications, require careful dosing and monitoring, and all carry some risk of bleeding. In recent years, several new targets have been identified, both in the platelet and coagulation systems, which may mitigate this bleeding risk. In this review, we briefly describe the current state of antithrombotic therapy, and then present a detailed discussion of the new generation of drugs that are being developed to target more safely existing or newly identified pathways, alongside the strategies to reverse direct oral anticoagulants, showcasing the breadth of approaches. Combined, these exciting advances in antithrombotic therapy bring us closer than we have ever been to the “holy grail” of the field, a treatment that separates the hemostatic and thrombotic systems, preventing clots without any concurrent bleeding risk.

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Novel approaches to antiplatelet therapy

Cited by 7 publications

References 210 publications

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Anticoagulant Macromolecules

Novel strategies in antithrombotic therapy: targeting thrombosis while preserving hemostasis

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