ArticleBlood2018
Targeting anticoagulant protein S to improve hemostasis in hemophilia.
Article in Blood, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 71 citations in OpenAlex.
- Mechanisms of thrombin inhibition by protein S and the TFPIα-fVshort-protein S complex.Biophysical journal · 2026Article
- Challenges in Balancing Hemostasis and Thrombosis in Therapy Tailoring for Hemophilia: A Narrative Review.International journal of molecular sciences · 2026Review
- Advancements in CRISPR-basedFrontiers in genome editing · 2026Review
- RNAi targeting heparin cofactor II promotes hemostasis in a canine model of acquired hemophilia A.Gene therapy · 2025Article
- Research Progress in In Vitro Screening Techniques for Natural Antithrombotic Medicines.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Emerging Therapies in Hemophilia: Improving Equitable Access to Care.Journal of blood medicine · 2025Review
- Review
- Emicizumab-mediated hemostatic function assessed by thrombin generation assay in an in vitro model of factor VIII-depleted thrombophilia plasma.International journal of hematology · 2024Article
- [Recent advances in the replacement therapy for Hemophilia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Article
- [Pathophysiology, diagnosis, and therapy for the management of acquired clotting factor deficiency].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Article
- Innovations in RNA therapy for hemophilia.Blood · 2023Review
- RNAi for the Treatment of People with Hemophilia: Current Evidence and Patient Selection.Journal of blood medicine · 2023Review
- Review
- Proteomic analysis of MSC-derived apoptotic vesicles identifies Fas inheritance to ameliorate haemophilia a via activating platelet functions.Journal of extracellular vesicles · 2022Article
- Thrombin spatial distribution determines protein C activation during hemostasis and thrombosis.Blood · 2022Article
- Factor-mimetic and rebalancing therapies in hemophilia A and B: the end of factor concentrates?Hematology. American Society of Hematology. Education Program · 2021Review
- Transient blood thinning during extracorporeal blood purification via the inactivation of coagulation factors by hydrogel microspheres.Nature biomedical engineering · 2021Article
- Natural anticoagulants: A missing link in mild to moderate bleeding tendencies.Haemophilia : the official journal of the World Federation of Hemophilia · 2021Review
- Barriers to antibody therapy in solid tumors, and their solutions.Cancer science · 2021Review
- Cerebral Cavernous Malformation: From Mechanism to Therapy.Circulation research · 2021Review
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Authors and funding
20 authors at 5 institutions in 5 countries.
Funding
Abstract
Improved treatments are needed for hemophilia A and B, bleeding disorders affecting 400 000 people worldwide. We investigated whether targeting protein S could promote hemostasis in hemophilia by rebalancing coagulation. Protein S (PS) is an anticoagulant acting as cofactor for activated protein C and tissue factor pathway inhibitor (TFPI). This dual role makes PS a key regulator of thrombin generation. Here, we report that targeting PS rebalances coagulation in hemophilia. PS gene targeting in hemophilic mice protected them against bleeding, especially when intra-articular. Mechanistically, these mice displayed increased thrombin generation, resistance to activated protein C and TFPI, and improved fibrin network. Blocking PS in plasma of hemophilia patients normalized in vitro thrombin generation. Both PS and TFPIα were detected in hemophilic mice joints. PS and TFPI expression was stronger in the joints of hemophilia A patients than in those of hemophilia B patients when receiving on-demand therapy, for example, during a bleeding episode. In contrast, PS and TFPI expression was decreased in hemophilia A patients receiving prophylaxis with coagulation factor concentrates, comparable to osteoarthritis patients. These results establish PS inhibition as both controller of coagulation and potential therapeutic target in hemophilia. The murine PS silencing RNA approach that we successfully used in hemophilic mice might constitute a new therapeutic concept for hemophilic patients.
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What OpenQuestion holds
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.