{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:11:21Z","timestamp":1790367081078,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia","award":["PCN-1-203\/N\/2\/K"],"award-info":[{"award-number":["PCN-1-203\/N\/2\/K"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The objective of this study was to evaluate the serum biomarkers implicated in the interaction of platelets and endothelium, as well as the efficacy of antiplatelet therapy in patients with aortic stenosis (AS) and coronary artery disease (CAD). A total of 78 adult patients with CAD on aspirin therapy participated in this study, including 49 consecutive patients with AS and 29 control subjects. The analysis included the following serum biomarkers: thrombomodulin (TM), platelet factor 4 (PF4), P-selectin, and CD40L. The efficacy of antiplatelet treatment was evaluated using the VerifyNow Aspirin test (ASPI test) and P2Y12 assay test (ADP test). Patients with AS exhibited increased serum levels of TM (7.64 \u00b1 3.5 ng\/mL vs. 6.28 \u00b1 2.1 ng\/mL, p = 0.011) and PF4 (25.16; Q1: 8.3; Q3: 29.6 \u03bcg\/mL vs. 12.85; Q1: 5.7; Q3: 14.5 \u03bcg\/mL, p = 0.021) compared to the control group. P-selectin and CD40L levels did not differ between groups. There were no significant differences in platelet aggregation in the ASPI (474.04 \u00b1 66.7 ARU vs. 471.31 \u00b1 56.2 ARU; p = 0.822) or ADP (224.88 \u00b1 46.4 PRU vs. 216.62 \u00b1 29.6 PRU; p = 0.394) tests. Bleeding incidence did not differ significantly between groups. The coexistence of AS in patients with CAD is associated with elevated levels of the aforementioned biomarkers, which are indicative of endothelial damage and platelet activation. However, the efficacy of antiplatelet treatment was independent of the presence of AS.<\/jats:p>","DOI":"10.3390\/ijms26157083","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T10:49:17Z","timestamp":1753267757000},"page":"7083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Platelet-Related Biomarkers and Efficacy of Antiplatelet Therapy in Patients with Aortic Stenosis and Coronary Artery Disease"],"prefix":"10.3390","volume":"26","author":[{"given":"Pawe\u0142","family":"Ba\u0144ka","sequence":"first","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Czepczor","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2195-1601","authenticated-orcid":false,"given":"Maciej","family":"Podolski","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6767-9586","authenticated-orcid":false,"given":"Agnieszka","family":"Kosowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5343-1205","authenticated-orcid":false,"given":"Wojciech","family":"Garczorz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-6090","authenticated-orcid":false,"given":"Tomasz","family":"Francuz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1151-8385","authenticated-orcid":false,"given":"Maciej","family":"Wybraniec","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6907-2799","authenticated-orcid":false,"given":"Katarzyna","family":"Mizia-Stec","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1093\/eurheartj\/ehy696","article-title":"Activated platelets promote an osteogenic programme and the progression of calcific aortic valve stenosis","volume":"40","author":"Bouchareb","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16006","DOI":"10.1038\/nrdp.2016.6","article-title":"Calcific aortic stenosis","volume":"2","author":"Lindman","year":"2016","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"791646","DOI":"10.3389\/fcvm.2021.791646","article-title":"The Complex Interplay of Inflammation, Metabolism, Epigenetics, and Sex in Calcific Disease of the Aortic Valve","volume":"8","author":"Ferrari","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"276","DOI":"10.31083\/j.rcm2508276","article-title":"Low-Density Lipoprotein Cholesterol, Type 2 Diabetes and Progression of Aortic Stenosis: The RED-CARPET Heart Valve Subgroup Cohort Study","volume":"25","author":"He","year":"2024","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.numecd.2015.02.001","article-title":"The lipid theory in the pathogenesis of calcific aortic stenosis","volume":"25","author":"Parisi","year":"2015","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114775","DOI":"10.1016\/j.biopha.2023.114775","article-title":"Oxidative stress and valvular endothelial cells in aortic valve calcification","volume":"163","author":"Shu","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ba\u0144ka, P., Wybraniec, M., Bochenek, T., Gruchlik, B., Burchacka, A., Swinarew, A., and Mizia-Stec, K. (2023). Influence of Aortic Valve Stenosis and Wall Shear Stress on Platelets Function. J. Clin. Med., 12.","DOI":"10.3390\/jcm12196301"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3233\/CH-200928","article-title":"Dynamic changes in platelets caused by shear stress in aortic valve stenosis","volume":"77","author":"Kanda","year":"2021","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1161\/01.CIR.102.11.1290","article-title":"Proteolysis of von Willebrand factor and shear stress-induced platelet aggregation in patients with aortic valve stenosis","volume":"102","author":"Pareti","year":"2000","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/labinvest.3700215","article-title":"The role of shear stress in the pathogenesis of atherosclerosis","volume":"85","author":"Cunningham","year":"2005","journal-title":"Lab. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1161\/ATVBAHA.119.312814","article-title":"Turbulent Flow Promotes Cleavage of VWF (von Willebrand Factor) by ADAMTS13 (A Disintegrin and Metalloproteinase with a Thrombospondin Type-1 Motif, Member 13)","volume":"39","author":"Bortot","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1007\/s10439-016-1577-7","article-title":"Flow-Induced Damage to Blood Cells in Aortic Valve Stenosis","volume":"44","author":"Vahidkhah","year":"2016","journal-title":"Ann. Biomed. Eng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1158\/1940-6207.CAPR-16-0241","article-title":"Unlocking Aspirin\u2019s Chemopreventive Activity: Role of Irreversibly Inhibiting Platelet Cyclooxygenase-1","volume":"10","author":"Lichtenberger","year":"2017","journal-title":"Cancer Prev. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1172\/JCI20986","article-title":"Central role of the P2Y12 receptor in platelet activation","volume":"113","author":"Dorsam","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.jacbts.2021.07.008","article-title":"Platelets: Implications in Aortic Valve Stenosis and Bioprosthetic Valve Dysfunction from Pathophysiology to Clinical Care","volume":"6","author":"Sellers","year":"2021","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1056\/NEJMoa022831","article-title":"Acquired von Willebrand syndrome in aortic stenosis","volume":"349","author":"Vincentelli","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1093\/eurheartj\/ehad277","article-title":"Heyde syndrome: Treat aortic valve disease to stop gastrointestinal bleeding?","volume":"44","author":"Waldschmidt","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1161\/CIRCULATIONAHA.122.062770","article-title":"Aspirin Versus Clopidogrel for Long-Term Maintenance Monotherapy After Percutaneous Coronary Intervention: The HOST-EXAM Extended Study","volume":"147","author":"Kang","year":"2023","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1016\/S0140-6736(21)01063-1","article-title":"Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): An investigator-initiated, prospective, randomised, open-label, multicentre trial","volume":"397","author":"Koo","year":"2021","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/S0140-6736(25)00449-0","article-title":"Efficacy and safety of clopidogrel versus aspirin monotherapy in patients at high risk of subsequent cardiovascular event after percutaneous coronary intervention (SMART-CHOICE 3): A randomised, open-label, multicentre trial","volume":"405","author":"Choi","year":"2025","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1182\/blood-2017-12-768994","article-title":"Exploring traditional and nontraditional roles for thrombomodulin","volume":"132","author":"Loghmani","year":"2018","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S0002-9440(10)61753-1","article-title":"Down-regulation of endothelial expression of endothelial cell protein C receptor and thrombomodulin in coronary atherosclerosis","volume":"159","author":"Laszik","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/cvr\/cvr220","article-title":"Thrombomodulin domains attenuate atherosclerosis by inhibiting thrombin-induced endothelial cell activation","volume":"92","author":"Wei","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.thromres.2009.11.023","article-title":"Role of the platelet chemokine platelet factor 4 (PF4) in hemostasis and thrombosis","volume":"125","author":"Kowalska","year":"2010","journal-title":"Thromb. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/ijlh.14075","article-title":"Platelet factor 4 triggers thrombo-inflammation by bridging innate and adaptive immunity","volume":"45","author":"Greinacher","year":"2023","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-0037-1614407","article-title":"The biology of P-selectin glycoprotein ligand-1: Its role as a selectin counterreceptor in leukocyte-endothelial and leukocyte-platelet interaction","volume":"81","author":"Yang","year":"1999","journal-title":"Thromb. Haemost."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.thromres.2011.04.018","article-title":"P-selectin ligation induces platelet activation and enhances microaggregate and thrombus formation","volume":"128","author":"Yacoub","year":"2011","journal-title":"Thromb. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ijcard.2005.09.051","article-title":"Soluble CD40 ligand and interleukin-6 in the coronary circulation after acute myocardial infarction","volume":"112","author":"Ohashi","year":"2006","journal-title":"Int. J. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"825892","DOI":"10.3389\/fimmu.2022.825892","article-title":"Platelets as Key Factors in Inflammation: Focus on CD40L\/CD40","volume":"13","author":"Cognasse","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1161\/ATVBAHA.115.307074","article-title":"Platelet CD40 Exacerbates Atherosclerosis by Transcellular Activation of Endothelial Cells and Leukocytes","volume":"36","author":"Gerdes","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2174\/138945012799424606","article-title":"Thrombomodulin links coagulation to inflammation and immunity","volume":"13","author":"Morser","year":"2012","journal-title":"Curr. Drug Targets"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/CIRCULATIONAHA.115.016757","article-title":"Autotaxin Derived from Lipoprotein(a) and Valve Interstitial Cells Promotes Inflammation and Mineralization of the Aortic Valve","volume":"132","author":"Bouchareb","year":"2015","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.carpath.2005.01.002","article-title":"Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis","volume":"14","author":"Kaden","year":"2005","journal-title":"Cardiovasc. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/jth.13533","article-title":"The association of anti-platelet factor 4\/heparin antibodies with early and delayed thromboembolism after cardiac surgery","volume":"15","author":"Welsby","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/09537104.2016.1240769","article-title":"Underlying mechanism and specific prevention of hemolysis-induced platelet activation","volume":"28","author":"Gremmel","year":"2017","journal-title":"Platelets"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1111\/jth.12422","article-title":"Mechanisms of hemolysis-associated platelet activation","volume":"11","author":"Helms","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e19336","DOI":"10.1097\/MD.0000000000019336","article-title":"Platelet activity with hemoglobin level in patients with hemodialysis: Prospective study","volume":"99","author":"Kim","year":"2020","journal-title":"Medicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1111\/jth.12376","article-title":"Hematocrit alters VerifyNow P2Y12 assay results independently of intrinsic platelet reactivity and clopidogrel responsiveness","volume":"11","author":"Kakouros","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.ahj.2014.06.029","article-title":"Does baseline hematocrit influence the assays of on-treatment platelet reactivity to clopidogrel?","volume":"168","author":"Pendyala","year":"2014","journal-title":"Am. Heart J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/jth.13642","article-title":"The effect of correcting VerifyNow P2Y12 assay results for hematocrit in patients undergoing percutaneous coronary interventions","volume":"15","author":"Janssen","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ahj.2017.03.006","article-title":"A laboratory association between hemoglobin and VerifyNow P2Y12 reaction unit: A systematic review and meta-analysis","volume":"188","author":"Kim","year":"2017","journal-title":"Am. Heart J."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lancellotti, P., Zamorano, J.Z., Habib, G., and Badano, L. (2016). The EACVI Textbook of Echocardiography (2 edn). The European Society of Cardiology Textbooks, Oxford University Press.","DOI":"10.1093\/med\/9780198726012.001.0001"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.thromres.2008.03.023","article-title":"Aspirin response evaluated by the VerifyNow Aspirin System and light transmission aggregometry","volume":"123","author":"Nielsen","year":"2008","journal-title":"Thromb. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ahj.2012.03.022","article-title":"Usefulness of the VerifyNow P2Y12 assay to evaluate the antiplatelet effects of ticagrelor and clopidogrel therapies","volume":"164","author":"Jeong","year":"2012","journal-title":"Am. Heart J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7083\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:14:28Z","timestamp":1760033668000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":44,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26157083"],"URL":"https:\/\/doi.org\/10.3390\/ijms26157083","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]}}}