{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T18:18:10Z","timestamp":1778350690745,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["UMO-2017\/27\/B\/NZ5\/02186"],"award-info":[{"award-number":["UMO-2017\/27\/B\/NZ5\/02186"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objectives: thromboembolic complications are a major cause of morbidity and mortality following Fontan (FO) surgery. It is also well established that altered FO circulation results in systemic complications, including liver and endothelium damage. We sought to evaluate whether dysfunctions of these sources of hemostatic factors may result in changes of fibrin clot properties. Methods: a permeation coefficient (Ks) and clot lysis time (CLT) were assessed in 66 FO patients, aged 23.0 years [IQR 19.3\u201327.0], and 59 controls, aged 24.0 years [IQR 19.0\u201329.0]. Ks was determined using a pressure-driven system. CLT value was measured according to assay described by Pieters et al. Endothelium and liver-derived hemostatic factors along with liver function parameters were evaluated. The median time between FO operation and investigation was 20.5 years [IQR 16.3\u201322.0]. Results: FO patients had lower Ks (p = 0.005) and prolonged CLT (p &lt; 0.001) compared to that of controls. Ks correlated with CLT (r = \u22120.28), FVIII (r = \u22120.30), FIX (r = \u22120.38), fibrinogen (r = \u22120.41), ALT (r = \u22120.25), AST (r = \u22120.26), GGTP (r = \u22120.27) and vWF antigen (r = \u22120.30), (all p &lt; 0.05). CLT correlated with the time between FO operation and investigation (r = 0.29) and FIX (r = 0.25), (all p &lt; 0.05). After adjustment for potential cofounders, TAFI antigen and GGTP were independent predictors of reduced Ks (OR 1.041 per 1% increase, 95% CI 1.009\u20131.081, p = 0.011 and OR 1.025 per 1 U\/L increase, 95% CI 1.005\u20131.053, p = 0.033, respectively). Protein C and LDL cholesterol predicted prolonged CLT (OR 1.078 per 1% increase, 95% CI 1.027\u20131.153, p = 0.001 and OR 6.360 per 1 \u03bcmol\/L increase, 95% CI 1.492\u201339.894, p = 0.011, respectively). Whereas elevated tPA was associated with lower risk of prolonged CLT (OR 0.550 per 1 ng\/mL, 95% CI 0.314\u20130.854, p = 0.004). GGTP correlated positively with time between FO surgery and investigation (r = 0.25, p = 0.045) and patients with abnormal elevated GGTP activity (n = 28, 42.4%) had decreased Ks, compared to that of the others (5.9 \u00d7 10\u22129 cm2 vs. 6.8 \u00d7 10\u22129 cm2, p = 0.042). Conclusion: our study shows that cellular liver damage and endothelial injury were associated with prothrombotic clot phenotype reflected by Ks and CLT.<\/jats:p>","DOI":"10.3390\/jcm10245976","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T08:43:32Z","timestamp":1639989812000},"page":"5976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Properties of Plasma Clots in Adult Patients Following Fontan Procedure: Relation to Clot Permeability and Lysis Time\u2014Multicenter Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6680-5504","authenticated-orcid":false,"given":"Maciej","family":"Skubera","sequence":"first","affiliation":[{"name":"Department of Cardiac and Vascular Diseases, John Paul II Hospital, 31-202 Krakow, Poland"},{"name":"Institute of Cardiology, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Go\u0142\u0105b","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Dentistry, Pomeranian Medical University, 70-204 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3687-512X","authenticated-orcid":false,"given":"Dariusz","family":"Plicner","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery and Transplantation, John Paul II Hospital, 31-202 Krakow, Poland"},{"name":"Unit of Experimental Cardiology and Cardiac Surgery, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Natorska","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, Jagiellonian University Medical College, 31-008 Krakow, Poland"},{"name":"Center for Research and Innovative Technology, John Paul II Hospital, 31-202 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1762-308X","authenticated-orcid":false,"given":"Micha\u0142","family":"Z\u0105bczyk","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, Jagiellonian University Medical College, 31-008 Krakow, Poland"},{"name":"Center for Research and Innovative Technology, John Paul II Hospital, 31-202 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Trojnarska","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Mazurek-Kula","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Polish Mother\u2019s Memorial Hospital, Research Institute, 93-338 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Sma\u015b-Suska","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Vascular Diseases, John Paul II Hospital, 31-202 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Bartczak-Rutkowska","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Podolec","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Vascular Diseases, John Paul II Hospital, 31-202 Krakow, Poland"},{"name":"Institute of Cardiology, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia","family":"Tomkiewicz-Paj\u0105k","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Vascular Diseases, John Paul II Hospital, 31-202 Krakow, Poland"},{"name":"Institute of Cardiology, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1177\/1076029613520464","article-title":"Thrombosis and thromboembolic complications in Fontan patients","volume":"20","author":"Firdouse","year":"2014","journal-title":"Clin. Appl. Thromb."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jacc.2011.01.061","article-title":"A multicenter, randomized trial comparing heparin\/warfarin and acetylsalicylic acid as primary thromboprophylaxis for 2 years after the Fontan procedure in children","volume":"58","author":"Monagle","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1161\/CIRCULATIONAHA.107.738559","article-title":"Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery","volume":"117","author":"Khairy","year":"2008","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s00246-007-9006-1","article-title":"Thromboembolism and the role of anticoagulation in the Fontan patient","volume":"28","author":"Jacobs","year":"2007","journal-title":"Pediatr. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1097\/MBC.0000000000000694","article-title":"In silico thrombin and factor Xa generation profiles in adult patients after Fontan operation","volume":"29","author":"Gissel","year":"2018","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_6","first-page":"70","article-title":"Altered endothelial function following the Fontan procedure","volume":"18","author":"Binotto","year":"2007","journal-title":"Cardiol. Young"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1253\/circj.CJ-08-1087","article-title":"Increased P-selectin expression on platelets and decreased plasma thrombomodulin in Fontan patients","volume":"73","author":"Kajimoto","year":"2009","journal-title":"Circ. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jjcc.2019.02.016","article-title":"Fontan-associated liver disease: A review","volume":"74","author":"Bove","year":"2019","journal-title":"J. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e001460","DOI":"10.1136\/openhrt-2020-001460","article-title":"Cross-sectional assessment of haemostatic profile and hepatic dysfunction in Fontan patients","volume":"8","author":"Daems","year":"2021","journal-title":"Open Heart"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"192","DOI":"10.5604\/01.3001.0010.8634","article-title":"Fontan-associated liver disease: A review","volume":"17","author":"Albillos","year":"2018","journal-title":"Ann. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1136\/heartjnl-2016-310108","article-title":"Factors associated with long-term mortality after Fontan procedures: A systematic review","volume":"103","author":"Alsaied","year":"2016","journal-title":"Heart"},{"key":"ref_12","first-page":"181","article-title":"Noninvasive assessment of liver status in adult Fontan patients","volume":"129","author":"Skubera","year":"2019","journal-title":"Pol. Arch. Int. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"873","DOI":"10.20452\/pamw.4165","article-title":"Plasma fibrin clot structure and thromboembolism: Clinical implications","volume":"127","author":"Undas","year":"2017","journal-title":"Pol. Arch. Int. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.blre.2014.09.003","article-title":"Fibrinolysis and the control of blood coagulation","volume":"29","author":"Chapin","year":"2015","journal-title":"Blood Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103487","DOI":"10.1016\/j.jprot.2019.103487","article-title":"Plasma fibrin clot proteomics in healthy subjects: Relation to clot permeability and lysis time","volume":"208","author":"Stachowicz","year":"2019","journal-title":"J. Proteom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1160\/TH11-11-0760","article-title":"Impaired fibrinolytic capacity and increased fibrin formation associate with myocardial infarction","volume":"107","author":"Leander","year":"2012","journal-title":"Thromb. Haemost."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103946","DOI":"10.1016\/j.jprot.2020.103946","article-title":"Plasma fibrin clot proteomics in patients with acute pulmonary embolism: Association with clot properties","volume":"229","author":"Bryk","year":"2020","journal-title":"J. Proteom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.jtcvs.2013.06.011","article-title":"Abnormalities in blood coagulation, fibrinolysis, and platelet activation in adult patients after the Fontan procedure","volume":"147","author":"Hoffman","year":"2014","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1159\/000205234","article-title":"Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens","volume":"17","author":"Clauss","year":"1957","journal-title":"Acta Haematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4272","DOI":"10.1182\/blood-2009-05-222380","article-title":"Altered fibrin clot structure\/function in patients with idiopathic venous thromboembolism and in their relatives","volume":"114","author":"Undas","year":"2009","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/jth.14002","article-title":"An international study on the feasibility of a standardized combined plasma clot turbidity and lysis assay: Communication from the SSC of the ISTH","volume":"16","author":"Pieters","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"711","DOI":"10.3748\/wjg.v21.i3.711","article-title":"Liver enzymes, metabolomics and genome-wide association studies: From systems biology to the personalized medicine","volume":"21","author":"Sookoian","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1053\/j.seminhematol.2013.06.003","article-title":"Hematologic manifestations of liver disease","volume":"50","author":"Marks","year":"2013","journal-title":"Semin. Hematol."},{"key":"ref_24","first-page":"160","article-title":"Endothelial function and hemostasis","volume":"89","author":"Becker","year":"2000","journal-title":"Z. Kardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.ijcard.2006.09.020","article-title":"Impaired vascular function in patients with Fontan circulation","volume":"120","author":"Jin","year":"2007","journal-title":"Int. J. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ijcard.2014.11.219","article-title":"Aspirin resistance in adult patients after Fontan surgery","volume":"181","author":"Wojcik","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/S0022-5223(02)73605-2","article-title":"Procoagulant and anticoagulant factor abnormalities following the Fontan procedure: Increased factor VIII may predispose to thrombosis","volume":"125","author":"Odegard","year":"2003","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1159\/000103655","article-title":"Hemostatic alterations in liver disease: A review on pathophysiology, clinical consequences, and treatment","volume":"24","author":"Lisman","year":"2007","journal-title":"Dig. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1160\/TH13-06-0479","article-title":"Improvement of fibrin clot structure after factor VIII injection in haemophilia A patients treated on demand","volume":"111","author":"Mikovic","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/jth.14011","article-title":"Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis","volume":"16","author":"Sinegre","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1055\/s-0037-1615651","article-title":"Low levels of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with chronic liver disease","volume":"85","author":"George","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/00004836-200203000-00013","article-title":"Update on nonalcoholic fatty liver disease","volume":"34","author":"McCullough","year":"2002","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1053\/euhj.2001.2807","article-title":"Prognostic value of serum gamma-glutamyl transferase activity after myocardial infarction","volume":"22","author":"Emdin","year":"2001","journal-title":"Eur. Heart J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1373\/clinchem.2006.078980","article-title":"\u03b3-glutamyltransferase as a predictor of chronic kidney disease in nonhypertensive and nondiabetic Korean men","volume":"53","author":"Ryu","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1016\/j.cjca.2019.07.625","article-title":"Protein-losing enteropathy following Fontan palliation","volume":"35","author":"Mackie","year":"2019","journal-title":"Can. J. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/j.jpeds.2012.11.073","article-title":"Low total, low-density lipoprotein, high-density lipoprotein, and non\u2013high-density lipoprotein cholesterol levels in patients with complex congenital heart disease after Fontan palliation","volume":"162","author":"Whiteside","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bj\u00f6rnsson, E.S. (2016). Hepatotoxicity by Drugs: The Most Common Implicated Agents. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17020224"},{"key":"ref_38","unstructured":"Undas, A., and Zabczyk, M. (2018). Antithrombotic medications and their impact on fibrin clot structure and function. J. Physiol. Pharmacol., 69."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/24\/5976\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:49:43Z","timestamp":1760168983000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/24\/5976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,20]]},"references-count":38,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["jcm10245976"],"URL":"https:\/\/doi.org\/10.3390\/jcm10245976","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,20]]}}}