{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:31:54Z","timestamp":1760059914402,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Else Kr\u00f6ner Fresenius Stiftung","award":["P27\/10\/\/A33\/10","GGER 9983"],"award-info":[{"award-number":["P27\/10\/\/A33\/10","GGER 9983"]}]},{"name":"Baxter","award":["P27\/10\/\/A33\/10","GGER 9983"],"award-info":[{"award-number":["P27\/10\/\/A33\/10","GGER 9983"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Coagulation disorders, including both bleeding and thrombotic complications, are common in patients undergoing hemodialysis (HD). Here, we aimed to characterize platelet function in patients undergoing hemodialysis three times per week, compared to healthy controls. Methods: Platelet function was assessed using the Multiplate analyzer (Roche), which is based on multiple electrode impedance aggregometry. Platelet aggregation was induced using adenosine diphosphate (ADP), and the area under the curve (AUC) served as the primary endpoint. In addition, platelet counts and C-reactive protein (CRP) levels were measured. To further evaluate nitric oxide (NO)-mediated inhibition of platelet aggregation, blood samples were incubated with the NO donor, sodium nitroprusside (SNP), and the phosphodiesterase 5A (PDE5A) inhibitor, sildenafil. Results: A total of 60 patients undergoing HD and 67 healthy controls were included in the analysis. Patients receiving HD treatment had significantly lower platelet counts compared to healthy controls (226.9 \u00b1 53.47 vs. 246.7 \u00b1 47.21 G\/L, p = 0.029). Platelet aggregation was markedly reduced in patients undergoing HD compared to controls (462.0 \u00b1 266.54 vs. 644.5 \u00b1 254.44 AU \u00d7 min, p &lt; 0.001) with a significant correlation for platelet count (r = 0.42, p = 0.001) and systemic inflammation as indicated by CRP levels (r = 0.28, p = 0.035). Following SNP and sildenafil administration, inhibition of platelet aggregation remained more pronounced in patients undergoing HD. However, the change in platelet aggregation after SNP\/sildenafil treatment did not differ significantly between the groups. Conclusions: Patients undergoing HD exhibit altered platelet function, indicated by reduced aggregation and platelet counts, as well as an association with systemic inflammation. Multiple electrode impedance aggregometry appears to be a feasible method for detecting platelet function alterations in patients receiving HD treatment. Responsiveness to NO donors was preserved in patients undergoing HD. Further studies are needed to identify the underlying mechanisms, particularly the role of NO signaling in platelet dysfunction in patients undergoing HD.<\/jats:p>","DOI":"10.3390\/jcm14145156","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:35:31Z","timestamp":1753094131000},"page":"5156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ex Vivo Thrombocyte Function and Its Response to NO\/Sildenafil in Patients Undergoing Hemodialysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Vera","family":"Bonell","sequence":"first","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany"},{"name":"Reparto di Nefrologia e Dialisi, Ospedale Centrale di Bolzano, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Schmaderer","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"G\u00fcnthner","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Angermann","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quirin","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudius","family":"K\u00fcchle","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lutz","family":"Renders","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Heemann","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Kessler","sequence":"additional","affiliation":[{"name":"Department of Cardiology, German Heart Center, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 80636 Munich, Germany"},{"name":"German Center for Cardiovascular Research (DZHK eV), Partner Site Munich Heart Alliance, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1242-4914","authenticated-orcid":false,"given":"Stephan","family":"Kemmner","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany"},{"name":"Transplant Center, University Hospital Munich, Ludwig-Maximilians-University (LMU), 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1525-139X.2006.00179.x","article-title":"Platelet dysfunction and end-stage renal disease","volume":"19","author":"Kaw","year":"2006","journal-title":"Semin. Dial."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1161\/01.HYP.0000102971.85504.7c","article-title":"Kidney disease as a risk factor for development of cardiovascular disease: A statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention","volume":"42","author":"Sarnak","year":"2003","journal-title":"Hypertension"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1046\/j.1523-1755.1999.00773.x","article-title":"Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency","volume":"56","author":"Culleton","year":"1999","journal-title":"Kidney Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1053\/ajkd.2002.34510","article-title":"Biphasic effects of hemodialysis on platelet reactivity in patients with end-stage renal disease: A potential contributor to cardiovascular risk","volume":"40","author":"Aggarwal","year":"2002","journal-title":"Am. J. Kidney Dis. Off. J. Natl. Kidney Found."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/ckj\/sft033","article-title":"Aspects of platelet disturbances in haemodialysis patients","volume":"6","author":"Schoorl","year":"2013","journal-title":"Clin. Kidney J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cca.2009.11.022","article-title":"Hemostatic changes in patients with end stage renal disease undergoing hemodialysis","volume":"411","author":"Rios","year":"2010","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/ki.2012.130","article-title":"Hemodialysis effect on platelet count and function and hemodialysis-associated thrombocytopenia","volume":"82","author":"Daugirdas","year":"2012","journal-title":"Kidney Int."},{"key":"ref_8","first-page":"306","article-title":"Reduced nitric oxide bioavailability in chronic renal failure: A new factor of progression?","volume":"25","author":"Bonomini","year":"2008","journal-title":"G. Ital. Di Nefrol. Organo Uff. Della Soc. Ital. Di Nefrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1681\/ASN.V85799","article-title":"Studies on platelet membrane glycoproteins and platelet function during hemodialysis","volume":"8","author":"Sloand","year":"1997","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_10","first-page":"2911","article-title":"Platelet activation in clinical haemodialysis: LMWH as a major contributor to bio-incompatibility?","volume":"23","author":"Gritters","year":"2008","journal-title":"Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc.-Eur. Ren. Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"van Bladel, E.R., de Jager, R.L., Walter, D., Cornelissen, L., Gaillard, C.A., Boven, L.A., Roest, M., and Fijnheer, R. (2012). Platelets of patients with chronic kidney disease demonstrate deficient platelet reactivity in vitro. BMC Nephrol., 13.","DOI":"10.1186\/1471-2369-13-127"},{"key":"ref_12","unstructured":"Kuter, D.J. (2024, November 01). Overview of Platelet Disorders. Available online: http:\/\/www.merckmanuals.com\/professional\/hematology-and-oncology\/thrombocytopenia-and-platelet-dysfunction\/overview-of-platelet-disorders."},{"key":"ref_13","unstructured":"National Heart, Lung and Blood Institute (2022, March 24). What Are Thrombocythemia and Thrombocytosis?, Available online: https:\/\/www.nhlbi.nih.gov\/health\/health-topics\/topics\/thrm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0160-5402(80)90024-8","article-title":"The electronic aggregometer: A novel device for assessing platelet behavior in blood","volume":"3","author":"Cardinal","year":"1980","journal-title":"J. Pharmacol. Methods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.athoracsur.2010.09.022","article-title":"Multiple electrode whole-blood aggregometry and bleeding in cardiac surgery patients receiving thienopyridines","volume":"91","author":"Ranucci","year":"2011","journal-title":"Ann. Thorac. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1160\/TH17-02-0129","article-title":"Whole blood ristocetin-activated platelet impedance aggregometry (Multiplate) for the rapid detection of Von Willebrand disease","volume":"117","author":"Schmidt","year":"2017","journal-title":"Thromb. Haemost."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.jacc.2008.11.030","article-title":"Platelet Reactivity After Clopidogrel Treatment Assessed with Point-of-Care Analysis and Early Drug-Eluting Stent Thrombosis","volume":"53","author":"Sibbing","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.jacc.2014.05.049","article-title":"Aspirin treatment and outcomes after percutaneous coronary intervention: Results of the ISAR-ASPI registry","volume":"64","author":"Mayer","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e005781","DOI":"10.1136\/bmjopen-2014-005781","article-title":"Individualising dual antiplatelet therapy after percutaneous coronary intervention: The IDEAL-PCI registry","volume":"4","author":"Christ","year":"2014","journal-title":"BMJ Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"786","DOI":"10.3174\/ajnr.A0917","article-title":"Monitoring of clopidogrel-related platelet inhibition: Correlation of nonresponse with clinical outcome in supra-aortic stenting","volume":"29","author":"Linn","year":"2008","journal-title":"AJNR. Am. J. Neuroradiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gomchok, D., Ge, R.-L., and Wuren, T. (2023). Platelets in Renal Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914724"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1111\/bph.15586","article-title":"Novel soluble guanylyl cyclase activators increase glomerular cGMP, induce vasodilation and improve blood flow in the murine kidney","volume":"179","author":"Stehle","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7772677","DOI":"10.1155\/2023\/7772677","article-title":"Immunophenotypic Characterization of Citrate-Containing A Concentrates in Maintenance Hemodialysis: A Pre-Post Study","volume":"2023","author":"Shen","year":"2023","journal-title":"Int. J. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2147\/VHRM.S44469","article-title":"Platelet function tests: A comparative review","volume":"11","author":"Paniccia","year":"2015","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"G\u00fcnthner, R., Lorenz, G., Braunisch, M.C., Angermann, S., Matschkal, J., Hausinger, R., Kuchler, T., Glaser, P., Schicktanz, F., and Haller, B. (2024). Endothelial dysfunction in retinal vessels of hemodialysis patients compared to healthy controls. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-64581-9"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1161\/CIRCULATIONAHA.116.024152","article-title":"Functional Characterization of the GUCY1A3 Coronary Artery Disease Risk Locus","volume":"136","author":"Kessler","year":"2017","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109120","DOI":"10.1016\/j.thromres.2024.109120","article-title":"A comparative study on the haemostatic changes in kidney failure patients: Pre- and post- haemodialysis and haemodiafiltration","volume":"242","author":"Jessica","year":"2024","journal-title":"Thromb. Res."},{"key":"ref_28","first-page":"359","article-title":"Uremic platelet dysfunction: Past and present","volume":"4","author":"Escolar","year":"2005","journal-title":"Curr. Hematol. Rep."},{"key":"ref_29","first-page":"823","article-title":"Abnormal cytoskeletal assembly in platelets from uremic patients","volume":"143","author":"Escolar","year":"1993","journal-title":"Am. J. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1046\/j.1525-1594.1999.06271.x","article-title":"Interactions between platelets and leukocytes during hemodialysis","volume":"23","author":"Bonomini","year":"1999","journal-title":"Artif. Organs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1111\/jth.13675","article-title":"Measurement of platelet aggregation, independently of patient platelet count: A flow-cytometric approach","volume":"15","author":"Vinholt","year":"2017","journal-title":"J. Thromb. Haemost. JTH"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1006\/meth.2000.1006","article-title":"Evaluation of platelet function by flow cytometry","volume":"21","author":"Michelson","year":"2000","journal-title":"Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.jacc.2010.03.048","article-title":"Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: Initial evidence of a therapeutic window","volume":"56","author":"Sibbing","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1160\/TH06-05-0242","article-title":"Multiple electrode aggregometry: A new device to measure platelet aggregation in whole blood","volume":"96","author":"Calatzis","year":"2006","journal-title":"Thromb. Haemost."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1159\/000184118","article-title":"Platelet count and thrombopoietic activity in patients with chronic renal failure","volume":"45","author":"Gafter","year":"1987","journal-title":"Nephron"},{"key":"ref_36","first-page":"352","article-title":"How Can I Manage Thrombocytopenia in Hemodialysis Patient? A Review","volume":"24","author":"Guo","year":"2020","journal-title":"Ther. Apher. Dial. Off. Peer-Rev. J. Int. Soc. Apher. Jpn. Soc. Apher. Jpn. Soc. Dial. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kraehling, J.R., Benardeau, A., Schomber, T., Popp, L., Vienenkoetter, J., Ellinger-Ziegelbauer, H., Pavkovic, M., Hartmann, E., Siudak, K., and Freyberger, A. (2023). The sGC Activator Runcaciguat Has Kidney Protective Effects and Prevents a Decline of Kidney Function in ZSF1 Rats. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713226"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Barale, C., and Russo, I. (2020). Influence of Cardiometabolic Risk Factors on Platelet Function. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020623"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/14\/5156\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:13:11Z","timestamp":1760033591000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/14\/5156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":38,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14145156"],"URL":"https:\/\/doi.org\/10.3390\/jcm14145156","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,7,21]]}}}