ArticleBlood2020
Thrombin activation of PAR-1 contributes to microvascular stasis in mouse models of sickle cell disease.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 41 citations in OpenAlex.
- Isoquercetin for thromboinflammation in sickle cell disease: a randomized double-blind placebo-controlled trial.Blood advances · 2024Trial
- Trial
- Acute therapy with hemopexin (CSL889) resolves LPS-induced lung vaso-occlusion in sickle mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Review
- Targeting PAR1 biased signaling with parmodulin reduces thromboinflammation and acute lung injury in sickle cell disease.Blood advances · 2026Article
- CD39 polymorphism enables lung thrombosis in sickle cell disease.Nature communications · 2026Article
- Protein S Enhances the Phagocytosis of Phosphatidylserine-Exposing Erythrocytes: Implications in Sickle Cell Disease.American journal of hematology · 2026Article
- crizanlizumab and inclacumab are equally potent inhibitors of cell adhesion in the blood of patients with sickle cell disease.Blood. Red cells & iron · 2025Article
- Emerging pathways in thromboinflammation of sickle cell disease: novel findings in disease pathogenesis.Research and practice in thrombosis and haemostasis · 2025Review
- Article
- Biased agonism of protease-activated receptor-1 regulates thromboinflammation in murine sickle cell disease.Blood advances · 2024Article
- Characterizing Modulators of Protease-activated Receptors with a Calcium Mobilization Assay Using a Plate Reader.Journal of visualized experiments : JoVE · 2024Article
- Mouse models of sickle cell disease: Imperfect and yet very informative.Blood cells, molecules & diseases · 2024Review
- Factor XII contributes to thrombotic complications and vaso-occlusion in sickle cell disease.Blood · 2023Article
- COVID-19 and Sickle Cell Disease: Two Independent Risk Factors for Venous Thromboembolism.Cureus · 2023Review
- Thrombo-Inflammation in COVID-19 and Sickle Cell Disease: Two Faces of the Same Coin.Biomedicines · 2023Review
- The APC-EPCR-PAR1 axis in sickle cell disease.Frontiers in medicine · 2023Review
- Evaluation of the mechanisms of heme-induced tissue factor activation: Contribution of innate immune pathways.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Article
- Antithrombin-III mitigates thrombin-mediated endothelial cell contraction and sickle red blood cell adhesion in microscale flow.British journal of haematology · 2022Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Vaso-occlusive crisis (VOC) is the primary cause of morbidity and hospitalization in sickle cell disease (SCD); however, only 4 therapies (hydroxyurea, l-glutamine, crizanlizumab, and voxeletor) are currently approved in SCD. These agents limit the duration, severity, and frequency of crises. Activation of coagulation is a hallmark of SCD. Studies in animal models of SCD have shown that coagulation contributes to the chronic inflammation and end-organ damage associated with the disease; however, it is unknown whether coagulation directly contributes to the microvascular stasis that causes VOC. Herein, we demonstrate that inhibition of tissue factor (TF) and the downstream coagulation proteases factor Xa and thrombin significantly attenuates heme-induced microvascular stasis in mouse models of VOC. Pharmacologic inhibition of the principal thrombin receptor, protease activated receptor-1 (PAR-1), as well as deficiency of PAR-1 in all nonhematopoietic cells, also reduces stasis in sickle mice. PAR-1 deficiency was associated with reduced endothelial von Willebrand factor expression, which has been shown to mediate microvascular stasis. In addition, TF inhibition reduces lung vaso-occlusion in sickle mice mediated by arteriolar neutrophil-platelet microemboli. In sum, these results suggest that prophylactic anticoagulation might attenuate the incidence of VOC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.