Illustrated State‐of‐the‐Art Capsules of the ISTH 2019 Congress in Melbourne, Australia

Ward, Christopher; Andrews, Robert K.

doi:10.1002/rth2.12225

Cited by 10 publications

(8 citation statements)

References 108 publications

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“…18,19 In sum, personalized approaches to treatment that integrate thrombus pathophysiology, circulating biomarkers, patient characteristics, and patient preferences require study. 20 determining duration of prophylaxis, 27,28 and in optimal treatment when VTE occurs in pregnant women. DVT treatment based on race and socioeconomic factors.…”

Section: T1 -Translational Research: From Animals To Humansmentioning

confidence: 99%

Venous thromboembolism research priorities: A scientific statement from the American Heart Association and the International Society on Thrombosis and Haemostasis

Cushman

Barnes

Creager

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Venous thromboembolism (VTE) is a major cause of morbidity and mortality. The impact of the Surgeon General's Call to Action in 2008 has been lower than expected given the public health impact of this disease. This scientific statement highlights future research priorities in VTE, developed by experts and a crowdsourcing survey across 16 scientific organizations. At the fundamental research level (T0), researchers need to identify pathobiologic causative mechanisms for the 50% of patients with unprovoked VTE and better understand mechanisms that differentiate hemostasis from thrombosis. At the human level (T1), new methods for diagnosing, treating, and preventing VTE will allow tailoring of diagnostic and therapeutic approaches to individuals. At the patient level (T2), research efforts are required to understand how foundational evidence impacts care of patients (eg, biomarkers). New treatments, such as catheter-based therapies, require further testing to identify which patients are most likely to experience benefit. At the practice level (T3), translating evidence into practice remains challenging. Areas of overuse and underuse will require evidence-based tools to improve care delivery. At the community and population level (T4), public awareness campaigns need thorough impact assessment. Large population-based cohort studies can elucidate the biologic and environmental underpinings of VTE and its complications. To achieve these goals, funding agencies and training

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Section: T1 -Translational Research: From Animals To Humansmentioning

confidence: 99%

Venous thromboembolism research priorities: A scientific statement from the American Heart Association and the International Society on Thrombosis and Haemostasis

Cushman

Barnes

Creager

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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“…This cytokine facilitates differentiation of luMCs into adMYFs, which generate elastic fibers to confer elasticity to the lung (Figure 6). 42 …”

Section: Role Of Platelet Clec‐2/pdpn In Lung Developmentmentioning

confidence: 99%

“…Transforming growth factor‐β (TGF‐β) is released from activated platelets and facilitates differentiation of lung mesothelial cells luMCs into alveolar duct myofibroblasts (adMYFs). AdMYFs generate elastic fibers so the lung can be properly inflated (cited from P.475 of Illustrated State‐of‐the‐Art Capsules of the ISTH 2019 congress in Melbourne, Australia 42 )…”

Section: Role Of Platelet Clec‐2/pdpn In Lung Developmentmentioning

confidence: 99%

Platelet CLEC‐2 and lung development

Suzuki‐Inoue

Tsukiji

2020

Research and Practice in Thrombosis and Haemostasis

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In this article, the State of the Art lecture “Platelet CLEC‐2 and Lung Development” presented at the ISTH congress 2019 is reviewed. During embryonic development, blood cells are often considered as porters of nutrition and oxygen but not as active influencers of cell differentiation. However, recent studies revealed that platelets actively facilitate cell differentiation by releasing biological substances during development. C‐type lectin‐like receptor 2 (CLEC‐2) has been identified as a receptor for the platelet‐activating snake venom rhodocytin. An endogenous ligand of CLEC‐2 is the membrane protein podoplanin (PDPN), which is expressed on the surface of certain types of tumor cells and lymphatic endothelial cells (LECs). Deletion of CLEC‐2 from platelets in mice results in death just after birth due to lung malformation and blood/lymphatic vessel separation. During development, lymphatic vessels are derived from cardinal veins. At this stage, platelets are activated by binding of CLEC‐2 to LEC PDPN and release trandforming growth factor‐β (TGF‐β). This cytokine inhibits LEC migration and proliferation, facilitating blood/lymphatic vessel separation. TGF‐β released upon platelet‐expressed CLEC‐2/LEC PDPN also facilitates differentiation of lung mesothelial cells into alveolar duct myofibroblasts (adMYFs) in the developing lung. AdMYFs generate elastic fibers inside the lung, so that the lung can be properly inflated. Thus, platelets act as an ultimate natural drug delivery system that enables biological substances to be specifically delivered to the target at high concentrations by receptor/ligand interactions during development.

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“…Later platelet responses, including procoagulant platelet function, is driven by PAR4. Reproduced with permission from Reference [31].…”

Section: Figurementioning

confidence: 99%

Using PAR4 Inhibition as an Anti-Thrombotic Approach: Why, How, and When?

Li¹,

Tarlac²,

Hamilton³

2019

IJMS

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Protease-activated receptors (PARs) are a family of four GPCRs with a variety of cellular functions, yet the only advanced clinical endeavours to target these receptors for therapeutic gain to date relates to the impairment of platelet function for anti-thrombotic therapy. The only approved PAR antagonist is the PAR1 inhibitor, vorapaxar—the sole anti-platelet drug against a new target approved in the past 20 years. However, there are two PARs on human platelets, PAR1 and PAR4, and more recent efforts have focused on the development of the first PAR4 antagonists, with first-in-class agents recently beginning clinical trial. Here, we review the rationale for this approach, outline the various modes of PAR4 inhibition, and speculate on the specific therapeutic potential of targeting PAR4 for the prevention of thrombotic conditions.

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Illustrated State‐of‐the‐Art Capsules of the ISTH 2019 Congress in Melbourne, Australia

Cited by 10 publications

References 108 publications

Venous thromboembolism research priorities: A scientific statement from the American Heart Association and the International Society on Thrombosis and Haemostasis

Venous thromboembolism research priorities: A scientific statement from the American Heart Association and the International Society on Thrombosis and Haemostasis

Platelet CLEC‐2 and lung development

Using PAR4 Inhibition as an Anti-Thrombotic Approach: Why, How, and When?

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