{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:23:55Z","timestamp":1792592635258,"version":"4.5.0"},"reference-count":39,"publisher":"Georg Thieme Verlag KG","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:p>\n            Background\u2003Cirrhotic patients display an increased risk for both bleeding and thrombosis. We investigated platelet activation across Child\u2013Pugh stages (CPSs) and portal hypertension (PH) severity.<\/jats:p><jats:p>\n            Material and Methods\u2003A total of 110 cirrhotic patients were prospectively included. CPS and hepatic venous pressure gradient (HVPG) were determined. Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb\/IIIa were measured by flow cytometry before\/after stimulation with protease-activated receptor (PAR)-1 (thrombin receptor activating peptide, TRAP) and PAR-4 (AYPGKF) agonists, epinephrine, and lipopolysaccharide (LPS).<\/jats:p><jats:p>\n            Results\u2003Platelet count was similar across CPS but lower with increasing PH severity. Expression of P-selectin and activated GPIIb\/IIIa in response to TRAP and AYPGKF was significantly reduced in platelets of CPS-B\/C versus CPS-A patients (all p\u2009&lt;\u20090.05). Platelet P-selectin expression upon epinephrine and LPS stimulation was reduced in CPS-C patients, while activated GPIIb\/IIIa in response to these agonists was lower in CPS-B\/C (all p\u2009&lt;\u20090.05). Regarding PH severity, P-selectin and activated GPIIb\/IIIa in response to AYPGKF were lower in HVPG \u226520 mmHg patients (both p\u2009&lt;\u20090.001 vs. HVPG\u2009&lt;\u200910 mmHg). Similarly, activated GPIIb\/IIIa was lower in HVPG \u226520 mmHg patients after TRAP stimulation (p\u2009&lt;\u20090.01 vs. HVPG\u2009&lt;\u200910 mmHg). The lower platelet surface expression of P-selectin and activated GPIIb\/IIIa upon stimulation of thrombin receptors (PAR-1\/PAR-4) in CPS-B\/C and HVPG \u226520 mmHg patients was paralleled by reduced antithrombin-III levels in those patients (all p\u2009&lt;\u20090.05). Overall, PAR-1- and PAR-4-mediated platelet activation correlated with antithrombin-III levels (p\u2009&lt;\u20090.001).<\/jats:p><jats:p>\n            Conclusion\u2003Platelet responsiveness decreases with increasing severity of liver cirrhosis and PH but is potentially counterbalanced by lower antithrombin-III levels.<\/jats:p>","DOI":"10.1055\/s-0043-1771187","type":"journal-article","created":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T22:32:45Z","timestamp":1690756365000},"page":"1140-1150","source":"Crossref","is-referenced-by-count":16,"title":["Platelet Function Decreases with Increasing Severity of Liver Cirrhosis and Portal Hypertension\u2014A Prospective Study"],"prefix":"10.1055","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-5875","authenticated-orcid":false,"given":"Ksenia","family":"Brusilovskaya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Experimental (HEPEX) Lab, Medical University of Vienna, Vienna, Austria"},{"name":"Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3403-3372","authenticated-orcid":false,"given":"Benedikt Silvester","family":"Hofer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Experimental (HEPEX) Lab, Medical University of Vienna, Vienna, Austria"},{"name":"Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-9146","authenticated-orcid":false,"given":"Benedikt","family":"Simbrunner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Experimental (HEPEX) Lab, Medical University of Vienna, Vienna, Austria"},{"name":"Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Eichelberger","sequence":"additional","affiliation":[{"name":"Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-8518","authenticated-orcid":false,"given":"David J. M.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2330-0017","authenticated-orcid":false,"given":"Mattias","family":"Mandorfer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7183-8076","authenticated-orcid":false,"given":"Philipp","family":"Schwabl","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Experimental (HEPEX) Lab, Medical University of Vienna, Vienna, Austria"},{"name":"Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Panzer","sequence":"additional","affiliation":[{"name":"Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4590-3583","authenticated-orcid":false,"given":"Thomas","family":"Reiberger","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Experimental (HEPEX) Lab, Medical University of Vienna, Vienna, Austria"},{"name":"Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9554-7292","authenticated-orcid":false,"given":"Thomas","family":"Gremmel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria"},{"name":"Department of Internal Medicine I, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-G\u00e4nserndorf, Mistelbach, Austria"},{"name":"Institute of Cardiovascular Pharmacotherapy and Interventional Cardiology, Karl Landsteiner Society, St. P\u00f6lten, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,7,30]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1056\/NEJMra1011170","article-title":"The coagulopathy of chronic liver disease","volume":"365","author":"A Tripodi","year":"2011","journal-title":"N Engl J Med"},{"issue":"06","key":"ref2","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.jhep.2021.11.004","article-title":"Haemostatic alterations and management of haemostasis in patients with cirrhosis","volume":"76","author":"T Lisman","year":"2022","journal-title":"J Hepatol"},{"issue":"06","key":"ref3","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1002\/hep.31201","article-title":"Hemostatic alterations in patients with cirrhosis: from primary hemostasis to fibrinolysis","volume":"71","author":"M G Zermatten","year":"2020","journal-title":"Hepatology"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0014-5793(87)80907-9","article-title":"Molecular mechanism underlying impaired platelet responsiveness in liver cirrhosis","volume":"220","author":"G Laffi","year":"1987","journal-title":"FEBS Lett"},{"issue":"06","key":"ref5","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1002\/hep.1840080625","article-title":"Altered platelet function in cirrhosis of the liver: impairment of inositol lipid and arachidonic acid metabolism in response to agonists","volume":"8","author":"G Laffi","year":"1988","journal-title":"Hepatology"},{"issue":"02","key":"ref6","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/0016-5085(92)90859-W","article-title":"Evidence for a storage pool defect in platelets from cirrhotic patients with defective aggregation","volume":"103","author":"G Laffi","year":"1992","journal-title":"Gastroenterology"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/0016-5085(93)90020-D","article-title":"Defective signal transduction in platelets from cirrhotics is associated with increased cyclic nucleotides","volume":"105","author":"G Laffi","year":"1993","journal-title":"Gastroenterology"},{"issue":"04","key":"ref8","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/S0168-8278(96)80164-4","article-title":"Defective aggregation in cirrhosis is independent of in vivo platelet activation","volume":"24","author":"G Laffi","year":"1996","journal-title":"J Hepatol"},{"issue":"05","key":"ref9","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1002\/hep.510240526","article-title":"Existence of a platelet-adhesion defect in patients with cirrhosis independent of hematocrit: studies under flow conditions","volume":"24","author":"A Ordinas","year":"1996","journal-title":"Hepatology"},{"issue":"39","key":"ref10","first-page":"818","article-title":"Activation of blood platelets in chronic hepatitis and liver cirrhosis P-selectin expression on blood platelets and secretory activity of beta-thromboglobulin and platelet factor-4","volume":"48","author":"A Panasiuk","year":"2001","journal-title":"Hepatogastroenterology"},{"issue":"01","key":"ref11","first-page":"41","article-title":"Platelet activation in patients with alcoholic liver disease","volume":"30","author":"F Ogasawara","year":"2005","journal-title":"Tokai J Exp Clin Med"},{"issue":"18","key":"ref12","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.3748\/wjg.v11.i18.2754","article-title":"Blood platelet and monocyte activations and relation to stages of liver cirrhosis","volume":"11","author":"A Panasiuk","year":"2005","journal-title":"World J Gastroenterol"},{"issue":"05","key":"ref13","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1080\/09537104.2017.1349308","article-title":"Reduced platelet activation and platelet aggregation in patients with alcoholic liver cirrhosis","volume":"29","author":"P J Vinholt","year":"2018","journal-title":"Platelets"},{"issue":"03","key":"ref14","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.jhep.2022.03.009","article-title":"Increased platelet aggregation in patients with decompensated cirrhosis indicates higher risk of further decompensation and death","volume":"77","author":"A Zanetto","year":"2022","journal-title":"J Hepatol"},{"issue":"11","key":"ref15","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1111\/j.1365-2036.2008.03674.x","article-title":"Review article: blood platelet number and function in chronic liver disease and cirrhosis","volume":"27","author":"P Witters","year":"2008","journal-title":"Aliment Pharmacol Ther"},{"issue":"02","key":"ref16","doi-asserted-by":"crossref","first-page":"xiii","DOI":"10.1016\/j.cld.2021.02.002","article-title":"Complications of cirrhosis","volume":"25","author":"A Cardenas","year":"2021","journal-title":"Clin Liver Dis"},{"issue":"06","key":"ref17","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jhepr.2019.10.001","article-title":"Platelets in chronic liver disease, from bench to bedside","volume":"1","author":"P Ramadori","year":"2019","journal-title":"JHEP Rep Innov Hepatol"},{"key":"ref18","first-page":"e58819","article-title":"Measurement of the hepatic venous pressure gradient and transjugular liver biopsy","volume":"160","author":"T Reiberger","year":"2020","journal-title":"J Vis Exp"},{"issue":"06","key":"ref19","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1080\/09537104.2021.2007868","article-title":"Peripheral versus central venous blood sampling does not influence the assessment of platelet activation in cirrhosis","volume":"33","author":"K Brusilovskaya","year":"2022","journal-title":"Platelets"},{"key":"ref20","author":"T Gremmel"},{"issue":"12","key":"ref21","doi-asserted-by":"crossref","first-page":"4925","DOI":"10.1182\/blood.V87.12.4925.bloodjournal87124925","article-title":"Flow cytometry: a clinical test of platelet function","volume":"87","author":"A D Michelson","year":"1996","journal-title":"Blood"},{"key":"ref22","author":"T A Blair"},{"key":"ref23","author":"K J Clemetson"},{"issue":"03","key":"ref24","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1055\/s-0035-1564835","article-title":"Platelet physiology","volume":"42","author":"T Gremmel","year":"2016","journal-title":"Semin Thromb Hemost"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1023\/B:THRO.0000014586.77684.82","article-title":"How platelets work: platelet function and dysfunction","volume":"16","author":"A D Michelson","year":"2003","journal-title":"J Thromb Thrombolysis"},{"issue":"03","key":"ref26","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/rth2.12115","article-title":"Novel aspects of antiplatelet therapy in cardiovascular disease","volume":"2","author":"T Gremmel","year":"2018","journal-title":"Res Pract Thromb Haemost"},{"issue":"01","key":"ref27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10557-019-06932-7","article-title":"Ticagrelor inhibits Toll-like and protease-activated receptor mediated platelet activation in acute coronary syndromes","volume":"34","author":"P P Wadowski","year":"2020","journal-title":"Cardiovasc Drugs Ther"},{"issue":"20","key":"ref28","doi-asserted-by":"crossref","first-page":"11189","DOI":"10.1073\/pnas.96.20.11189","article-title":"Protease-activated receptor 1 is the primary mediator of thrombin-stimulated platelet procoagulant activity","volume":"96","author":"H Andersen","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref29","first-page":"2314","article-title":"Platelet function in thrombocytopenic patients with chronic liver disease","volume":"130","author":"E Smolensky Koganov","year":"2017","journal-title":"Blood"},{"issue":"02","key":"ref30","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1182\/blood.V71.2.494.494","article-title":"Differential requirements for platelet aggregation and inhibition of adenylate cyclase by epinephrine. Studies of a familial platelet alpha 2-adrenergic receptor defect","volume":"71","author":"A K Rao","year":"1988","journal-title":"Blood"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"172798","DOI":"10.1016\/j.ejphar.2019.172798","article-title":"Epinephrine restores platelet functions inhibited by ticagrelor: a mechanistic approach","volume":"866","author":"A C Martin","year":"2020","journal-title":"Eur J Pharmacol"},{"issue":"07","key":"ref32","first-page":"614","article-title":"Evaluation of acquired platelet dysfunctions in uremic and cirrhotic patients using the platelet function analyzer (PFA-100 ): influence of hematocrit elevation","volume":"84","author":"G Escolar","year":"1999","journal-title":"Haematologica"},{"issue":"03","key":"ref33","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: pathophysiological basis for therapy","volume":"72","author":"A Albillos","year":"2020","journal-title":"J Hepatol"},{"issue":"02","key":"ref34","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/hep.28853","article-title":"Low-grade endotoxemia and platelet activation in cirrhosis","volume":"65","author":"V Raparelli","year":"2017","journal-title":"Hepatology"},{"issue":"08","key":"ref35","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1136\/gutjnl-2019-319044","article-title":"Role of portal venous platelet activation in patients with decompensated cirrhosis and TIPS","volume":"69","author":"A Queck","year":"2020","journal-title":"Gut"},{"issue":"05","key":"ref36","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/ejh.12262","article-title":"An overview of platelet indices and methods for evaluating platelet function in thrombocytopenic patients","volume":"92","author":"P J Vinholt","year":"2014","journal-title":"Eur J Haematol"},{"issue":"06","key":"ref37","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1111\/liv.13317","article-title":"Thrombocytopenia in chronic liver disease","volume":"37","author":"M Peck-Radosavljevic","year":"2017","journal-title":"Liver Int"},{"issue":"01","key":"ref38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/hep.21231","article-title":"Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity","volume":"44","author":"T Lisman","year":"2006","journal-title":"Hepatology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1477-9560-4-19","article-title":"Antithrombin significantly influences platelet adhesion onto immobilized fibrinogen in an in-vitro system simulating low flow","volume":"4","author":"R Loncar","year":"2006","journal-title":"Thromb J"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-1771187.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T23:31:39Z","timestamp":1701300699000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-1771187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,30]]},"references-count":39,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,11,29]]},"published-print":{"date-parts":[[2023,12]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-1771187","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,30]]}}}