ArticleThrombosis and haemostasis2013
Platelet protein S directly inhibits procoagulant activity on platelets and microparticles.
Article in Thrombosis and haemostasis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 28 citations in OpenAlex.
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- Mechanisms of thrombin inhibition by protein S and the TFPIα-fVshort-protein S complex.Biophysical journal · 2026Article
- Platelet Microvesicles, Inflammation, and Coagulation Markers: A Pilot Study.Hematology reports · 2023Article
- Activated protein C, protein S, and tissue factor pathway inhibitor cooperate to inhibit thrombin activation.Thrombosis research · 2023Article
- Review
- Immunothrombosis and the Role of Platelets in Venous Thromboembolic Diseases.International journal of molecular sciences · 2022Review
- The severity and duration of Hypoglycemia affect platelet-derived protein responses in Caucasians.Cardiovascular diabetology · 2022Article
- Dysregulation of Protein S in COVID-19.Best practice & research. Clinical haematology · 2022Review
- Interplay between platelets and coagulation.Blood reviews · 2021Review
- Platelet anticoagulant proteins: Modulators of thrombosis propensity within a procoagulant cell.Journal of thrombosis and haemostasis : JTH · 2020Article
- A novel mutation Gly222Arg in PROS1 causing protein S deficiency in a patient with pulmonary embolism.Journal of clinical laboratory analysis · 2020Article
- Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome.Frontiers in immunology · 2020Article
- Platelet-Derived Microvesicles in Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2017Review
- Phospholipid Binding Protein C Inhibitor (PCI) Is Present on Microparticles Generated In Vitro and In Vivo.PloS one · 2015Article
- Protein S is a cofactor for platelet and endothelial tissue factor pathway inhibitor-α but not for cell surface-associated tissue factor pathway inhibitor.Arteriosclerosis, thrombosis, and vascular biology · 2014Article
- Plasma protein S residues 37-50 mediate its binding to factor Va and inhibition of blood coagulation.Thrombosis and haemostasis · 2013Article
- Phosphorylation of protein S by platelet kinases enhances its activated protein C cofactor activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- State of the art in platelet function testing.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Anticoagulant plasma protein S (PS) is essential for maintaining haemostatic balance. About 2.5% of PS is stored in platelets and released upon platelet stimulation. So far, little is known about the functionality and importance of platelet (plt)PS. A platelet-associated protease cleaves plasma-derived (pd)PS and pltPS in the "thrombin-sensitive region", abolishing activated protein C (APC) cofactor activity. However, we showed that cleaved PS retains APC-independent anticoagulant activities ("PS-direct"). To investigate whether pltPS or pdPS exert PS-direct on platelets or platelet-shed microparticles, thrombin and factor (F)Xa generation on unstimulated or stimulated washed platelets and microparticles were measured. Western blotting revealed that pltPS and pdPS bound to washed, stimulated platelets and microparticles, and that pltPS had slower electrophoretic mobility than pdPS. Platelet stimulation in the presence of inhibitory anti-PS antibodies resulted in 2.6 ± 1.6-fold (p<0.0004, n=20) more thrombin generation upon addition of FXa and prothrombin. PltPS exerted PS-direct that was similar to or greater than that of Zn(2+)-containing pdPS and much greater than that of Zn(2+)-deficient pdPS. Findings were confirmed using purified pltPS. Platelet-bound pltPS and microparticle-bound pltPS had similar PS-direct. Finally, platelet stimulation in the presence of inhibitory anti-PS antibodies resulted in 1.5 ± 0.2-fold (p<0.0001, n=11) more FXa generation upon addition of TF/FVIIa and FX. Thus, pltPS inhibits both prothrombinase and extrinsic FXase activities. Neutralising antibodies against APC and TFPI had no effect on the PS-direct of pltPS or pdPS on platelets. This study indicates that pltPS may be an essential pool of PS that counterbalances procoagulant activities on platelets.
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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.