{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:32:54Z","timestamp":1789144374306,"version":"build-2803163510"},"reference-count":100,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T00:00:00Z","timestamp":1588723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Changes in primary hemostasis have been described in patients with chronic liver disease (CLD) and cirrhosis and are still subject to ongoing debate. Thrombocytopenia is common and multifactorial. Numerous studies also reported platelet dysfunction. In spite of these changes, primary hemostasis seems to be balanced. Patients with CLD and cirrhosis can suffer from both hemorrhagic and thrombotic complications. Variceal bleeding is the major hemorrhagic complication and is mainly determined by high portal pressure. Non portal hypertension-related bleeding due to hemostatic failure is uncommon. Thrombocytopenia can complicate management of invasive procedures in CLD patients. Recently, oral thrombopoietin agonists have been approved to raise platelets before invasive procedures. In this review we aim to bundle literature, published over the past decade, discussing primary hemostasis in CLD and cirrhosis including (1) platelet count and the role of thrombopoietin (TPO) agonists, (2) platelet function tests and markers of platelet activation, (3) von Willebrand factor and (4) global hemostasis tests.<\/jats:p>","DOI":"10.3390\/ijms21093294","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T03:10:38Z","timestamp":1588821038000},"page":"3294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Primary Hemostasis in Chronic Liver Disease and Cirrhosis: What Did We Learn over the Past Decade?"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7056-7123","authenticated-orcid":false,"given":"Marie-Astrid","family":"van Dievoet","sequence":"first","affiliation":[{"name":"D\u00e9partement des Laboratoires Cliniques, Cliniques universitaires Saint-Luc, 1200 Brussels, Belgium"},{"name":"Laboratoire d\u2019H\u00e9patologie P\u00e9diatrique et Th\u00e9rapie Cellulaire, Unit\u00e9 PEDI, Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), Universit\u00e9 Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Eeckhoudt","sequence":"additional","affiliation":[{"name":"D\u00e9partement des Laboratoires Cliniques, Cliniques universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Stephenne","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019H\u00e9patologie P\u00e9diatrique et Th\u00e9rapie Cellulaire, Unit\u00e9 PEDI, Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), Universit\u00e9 Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium"},{"name":"Service de Gastro-Ent\u00e9rologie et H\u00e9patologie P\u00e9diatrique, D\u00e9partement de P\u00e9diatrie, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1055\/s-0035-1550430","article-title":"Rebalanced Hemostasis in Patients with Acute Liver Failure","volume":"41","author":"Lisman","year":"2015","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1056\/NEJMra1011170","article-title":"The coagulopathy of chronic liver disease","volume":"365","author":"Tripodi","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1053\/j.gastro.2006.09.013","article-title":"Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: A systematic review","volume":"131","author":"Luca","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1136\/gutjnl-2015-309262","article-title":"U.K. guidelines on the management of variceal haemorrhage in cirrhotic patients","volume":"64","author":"Tripathi","year":"2015","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/liv.13500","article-title":"Decreased portal vein velocity is predictive of the development of portal vein thrombosis: A matched case-control study","volume":"38","author":"Stine","year":"2018","journal-title":"Liver Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1160\/TH16-06-0450","article-title":"The risk of venous thromboembolism in patients with cirrhosis. A systematic review and meta-analysis","volume":"117","author":"Ambrosino","year":"2017","journal-title":"Thromb. Haemost."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1053\/j.gastro.2012.07.018","article-title":"Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis","volume":"143","author":"Villa","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1111\/j.1478-3231.2011.02617.x","article-title":"NADPH oxidase-mediated platelet isoprostane over-production in cirrhotic patients: Implication for platelet activation","volume":"31","author":"Basili","year":"2011","journal-title":"Liver Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1111\/j.1538-7836.2010.03937.x","article-title":"Enhanced thrombin generation in patients with cirrhosis-induced coagulopathy","volume":"8","author":"Gatt","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1111\/jth.13278","article-title":"Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen","volume":"14","author":"Hugenholtz","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.jhep.2011.06.008","article-title":"Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction?","volume":"55","author":"Violi","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/hep.23653","article-title":"Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple laboratory method","volume":"52","author":"Tripodi","year":"2010","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1097\/TP.0b013e318250fc25","article-title":"Transfusion rate for 500 consecutive liver transplantations: Experience of one liver transplantation center","volume":"93","author":"Massicotte","year":"2012","journal-title":"Transplantation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1111\/j.1572-0241.2000.02325.x","article-title":"Prevalence of peripheral blood cytopenias (hypersplenism) in patients with nonalcoholic chronic liver disease","volume":"95","author":"Bashour","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1111\/j.1538-7836.2006.02122.x","article-title":"No evidence for an intrinsic platelet defect in patients with liver cirrhosis--studies under flow conditions","volume":"4","author":"Lisman","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_16","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":"Lisman","year":"2006","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/ajg.2017.457","article-title":"Platelet Count Does Not Predict Bleeding in Cirrhotic Patients: Results from the PRO-LIVER Study","volume":"113","author":"Basili","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1111\/liv.13317","article-title":"Thrombocytopenia in chronic liver disease","volume":"37","year":"2017","journal-title":"Liver Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1055\/s-0037-1604091","article-title":"Platelets as Modulators of Liver Diseases","volume":"44","author":"Lisman","year":"2018","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/MEG.0000000000001272","article-title":"Role of the von Willebrand factor and the VITRO score as predictors for variceal bleeding in patients with hepatitis C-related cirrhosis","volume":"31","author":"Ibrahim","year":"2019","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/00365521.2019.1578822","article-title":"Blood platelet function abnormalities in cirrhotic patients with esophageal varices in relation to the variceal bleeding history","volume":"54","author":"Rogalski","year":"2019","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1053\/j.gastro.2012.10.001","article-title":"Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis","volume":"144","author":"Berzigotti","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3904\/kjim.2014.152","article-title":"Bleeding complications in critically ill patients with liver cirrhosis","volume":"31","author":"Cho","year":"2016","journal-title":"Korean J. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1053\/j.gastro.2019.03.070","article-title":"AGA Clinical Practice Update: Coagulation in Cirrhosis","volume":"157","author":"Greenberg","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"220","DOI":"10.4103\/sjg.SJG_486_17","article-title":"Association of coagulopathy with the risk of bleeding after invasive procedures in liver cirrhosis","volume":"24","author":"Li","year":"2018","journal-title":"Saudi J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.cgh.2010.03.025","article-title":"Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial","volume":"8","author":"Seeff","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/hep.21266","article-title":"Thrombin generation in patients with cirrhosis: The role of platelets","volume":"44","author":"Tripodi","year":"2006","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.cgh.2010.06.018","article-title":"Incidence of bleeding following invasive procedures in patients with thrombocytopenia and advanced liver disease","volume":"8","author":"Giannini","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ejim.2016.11.007","article-title":"Bleeding after invasive procedures is rare and unpredicted by platelet counts in cirrhotic patients with thrombocytopenia","volume":"38","author":"Napolitano","year":"2017","journal-title":"Eur. J. Intern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/liv.12038","article-title":"Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion","volume":"33","author":"Tripodi","year":"2013","journal-title":"Liver Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.jhep.2008.03.009","article-title":"Thrombocytopenia associated with chronic liver disease","volume":"48","author":"Afdhal","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_32","first-page":"39","article-title":"The pathophysiology of thrombocytopenia in chronic liver disease","volume":"8","author":"Mitchell","year":"2016","journal-title":"Hepat. Med."},{"key":"ref_33","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":"Witters","year":"2008","journal-title":"Aliment. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/369519a0","article-title":"Blood. Thrombopoietin--at last","volume":"369","author":"Metcalf","year":"1994","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1055\/s-0037-1615024","article-title":"Evaluation of thrombopoiesis in thrombocytopenic disorders by simultaneous measurement of reticulated platelets of whole blood and serum thrombopoietin concentrations","volume":"79","author":"Koike","year":"1998","journal-title":"Thromb. Haemost."},{"key":"ref_36","first-page":"1645","article-title":"Serum thrombopoietin levels in patients with chronic hepatitis and liver cirrhosis, and its relationship with circulating thrombocyte counts","volume":"49","author":"Koruk","year":"2002","journal-title":"Hepatogastroenterology"},{"key":"ref_37","first-page":"1124","article-title":"Reticulated platelets as a marker of megakaryopoiesis in liver cirrhosis; relation to thrombopoietin and hepatocyte growth factor serum concentration","volume":"51","author":"Panasiuk","year":"2004","journal-title":"Hepatogastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1440-1746.2006.04359.x","article-title":"Evaluation of platelet kinetics in patients with liver cirrhosis: Similarity to idiopathic thrombocytopenic purpura","volume":"22","author":"Kajihara","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1046\/j.1440-1746.2003.03026.x","article-title":"Role of elevated platelet-associated immunoglobulin G and hypersplenism in thrombocytopenia of chronic liver diseases","volume":"18","author":"Sanjo","year":"2003","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1572-0241.1998.080_c.x","article-title":"Regulation of hepatic thrombopoietin production by portal hemodynamics in liver cirrhosis","volume":"93","author":"Sezai","year":"1998","journal-title":"Am. J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S1386-6346(01)00170-X","article-title":"Thrombopoietin receptor (c-Mpl) is constitutively expressed on platelets of patients with liver cirrhosis, and correlates with its disease progression","volume":"23","author":"Ishikawa","year":"2002","journal-title":"Hepatol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1002\/hep.510290627","article-title":"Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood","volume":"29","author":"Wolber","year":"1999","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1056\/NEJMoa1110709","article-title":"Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia","volume":"367","author":"Afdhal","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.cgh.2018.11.047","article-title":"Lusutrombopag Reduces Need for Platelet Transfusion in Patients With Thrombocytopenia Undergoing Invasive Procedures","volume":"17","author":"Hidaka","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/hep.30561","article-title":"Lusutrombopag for the Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Invasive Procedures (L-PLUS 2)","volume":"70","author":"Simon","year":"2019","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1053\/j.gastro.2018.05.025","article-title":"Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia","volume":"155","author":"Terrault","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/lt.22089","article-title":"Thrombelastograph platelet mapping in a patient receiving antiplatelet therapy","volume":"16","author":"Pivalizza","year":"2010","journal-title":"Liver Transpl."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Nielsen, N.S., Jespersen, S., Gaardbo, J.C., Arnbjerg, C.J., Clausen, M.R., Kjaer, M., Gerstoft, J., Ballegaard, V., Ostrowski, S.R., and Nielsen, S.D. (2017). Impaired Platelet Aggregation and Rebalanced Hemostasis in Patients with Chronic Hepatitis C Virus Infection. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18051016"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.thromres.2009.06.011","article-title":"Dependence of platelet function on underlying liver disease in orthotopic liver transplantation","volume":"124","author":"Juttner","year":"2009","journal-title":"Thromb. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.clinre.2016.03.008","article-title":"Portal vein thrombosis in cirrhosis is not associated with intestinal barrier disruption or increased platelet aggregability","volume":"40","author":"Wosiewicz","year":"2016","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e13390","DOI":"10.1111\/petr.13390","article-title":"Novel insights into the assessment of risk of upper gastrointestinal bleeding in decompensated cirrhotic children","volume":"23","author":"Bonnet","year":"2019","journal-title":"Pediatr. Transpl."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e0200364","DOI":"10.1371\/journal.pone.0200364","article-title":"Evolution of platelet functions in cirrhotic patients undergoing liver transplantation: A prospective exploration over a month","volume":"13","author":"Eyraud","year":"2018","journal-title":"PLoS ONE"},{"key":"ref_53","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":"Vinholt","year":"2018","journal-title":"Platelets"},{"key":"ref_54","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":"Raparelli","year":"2017","journal-title":"Hepatology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.thromres.2014.11.016","article-title":"No evidence for increased platelet activation in patients with hepatitis B- or C-related cirrhosis and hepatocellular carcinoma","volume":"135","author":"Alkozai","year":"2015","journal-title":"Thromb. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.jhep.2016.06.001","article-title":"Preserved hemostatic status in patients with non-alcoholic fatty liver disease","volume":"65","author":"Potze","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1055\/s-0038-1676954","article-title":"Haemostatic Profiles are Similar across All Aetiologies of Cirrhosis","volume":"119","author":"Bos","year":"2019","journal-title":"Thromb. Haemost."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e228","DOI":"10.1016\/j.thromres.2009.12.002","article-title":"Monocyte-platelet aggregates and platelet micro-particles in patients with post-hepatitic liver cirrhosis","volume":"125","author":"Sayed","year":"2010","journal-title":"Thromb. Res."},{"key":"ref_59","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":"Panasiuk","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1111\/apt.14600","article-title":"Platelet-leucocyte aggregation is augmented in cirrhosis and further increased by platelet transfusion","volume":"47","author":"Stoy","year":"2018","journal-title":"Aliment. Pharm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.dld.2014.02.021","article-title":"Polyunsaturated fatty acids balance affects platelet NOX2 activity in patients with liver cirrhosis","volume":"46","author":"Basili","year":"2014","journal-title":"Dig. Liver Dis."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Queck, A., Carnevale, R., Uschner, F.E., Schierwagen, R., Klein, S., Jansen, C., Meyer, C., Praktiknjo, M., Thomas, D., and Strassburg, C. (2019). Role of portal venous platelet activation in patients with decompensated cirrhosis and TIPS. Gut.","DOI":"10.1136\/gutjnl-2019-319044"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e0222840","DOI":"10.1371\/journal.pone.0222840","article-title":"Pathophysiological role of prostanoids in coagulation of the portal venous system in liver cirrhosis","volume":"14","author":"Queck","year":"2019","journal-title":"PLoS ONE"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s11239-016-1401-0","article-title":"Increased soluble GPVI levels in cirrhosis: Evidence for early in vivo platelet activation","volume":"43","author":"Egan","year":"2017","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s11239-016-1405-9","article-title":"Assessing in vivo platelet activation in patients with liver diseases","volume":"43","author":"Lisman","year":"2017","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1111\/j.1478-3231.2011.02737.x","article-title":"Pitfalls in assessing platelet activation status in patients with liver disease","volume":"32","author":"Lisman","year":"2012","journal-title":"Liver Int."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/17474086.2019.1562333","article-title":"Platelet function assays in diagnosis: An update","volume":"12","author":"Gresele","year":"2019","journal-title":"Expert Rev. Hematol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"63","DOI":"10.7123\/01.EJH.0000427964.00166.73","article-title":"Evaluation of platelet dysfunction in viral liver cirrhosis (relationship to disease severity)","volume":"38","author":"Ghozlan","year":"2013","journal-title":"Egypt. J. Haematol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e112583","DOI":"10.1371\/journal.pone.0112583","article-title":"Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis","volume":"9","author":"Wannhoff","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1097\/MEG.0000000000000442","article-title":"Usefulness of thromboelastometry in predicting the risk of bleeding in cirrhotics who undergo invasive procedures","volume":"27","author":"Ponzo","year":"2015","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s12185-009-0481-4","article-title":"Pivotal role of ADAMTS13 function in liver diseases","volume":"91","author":"Uemura","year":"2010","journal-title":"Int. J. Hematol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1055\/s-0038-1661393","article-title":"Major Changes of von Willebrand Factor Multimer Distribution in Cirrhotic Patients with Stable Disease or Acute Decompensation","volume":"118","author":"Palyu","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.3109\/00365521.2015.1037346","article-title":"von Willebrand factor as a novel noninvasive predictor of portal hypertension and esophageal varices in hepatitis B patients with cirrhosis","volume":"50","author":"Wu","year":"2015","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1002\/hep.28703","article-title":"High von Willebrand factor antigen levels and procoagulant imbalance may be involved in both increasing severity of cirrhosis and portal vein thrombosis","volume":"64","author":"Kalambokis","year":"2016","journal-title":"Hepatology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.jhep.2016.06.002","article-title":"von Willebrand factor and procoagulant imbalance predict outcome in patients with cirrhosis and thrombocytopenia","volume":"65","author":"Kalambokis","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jcrc.2017.07.053","article-title":"Balanced haemostasis with both hypo- and hyper-coagulable features in critically ill patients with acute-on-chronic-liver failure","volume":"43","author":"Fisher","year":"2018","journal-title":"J. Crit. Care"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1097\/MBC.0000000000000009","article-title":"Changes in the levels of endothelium-derived coagulation parameters in nonalcoholic fatty liver disease","volume":"25","author":"Bilgir","year":"2014","journal-title":"Blood Coagul. Fibrinolysis Int. J. Haemost. Thromb."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1007\/BF02781922","article-title":"Histochemical properties of vascular and sinusoidal endothelial cells in liver diseases","volume":"26","author":"Hattori","year":"1991","journal-title":"Gastroenterol. Jpn."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1111\/liv.12765","article-title":"Infusion of DDAVP does not improve primary hemostasis in patients with cirrhosis","volume":"35","author":"Arshad","year":"2015","journal-title":"Liver Int."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.joms.2009.07.081","article-title":"Intranasal desmopressin versus blood transfusion in cirrhotic patients with coagulopathy undergoing dental extraction: A randomized controlled trial","volume":"68","author":"Stanca","year":"2010","journal-title":"J. Oral Maxillofac Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1182\/blood-2005-01-0152","article-title":"Localization of ADAMTS13 to the stellate cells of human liver","volume":"106","author":"Uemura","year":"2005","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/labinvest.3700275","article-title":"ADAMTS13 is expressed in hepatic stellate cells","volume":"85","author":"Zhou","year":"2005","journal-title":"Lab. Investig. A J. Tech. Methods Pathol."},{"key":"ref_83","unstructured":"Michelson, M.C., Andrew, F., and Peter, N. (2019). Chapter 33: Clinical tests of platelet function. Platelets, Academic Press. [4th ed.]."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.thromres.2008.11.008","article-title":"The coagulopathy of cirrhosis assessed by thromboelastometry and its correlation with conventional coagulation parameters","volume":"124","author":"Tripodi","year":"2009","journal-title":"Thromb. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1111\/j.1537-2995.2011.03526.x","article-title":"An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation","volume":"52","author":"Blasi","year":"2012","journal-title":"Transfusion"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1016\/j.transproceed.2015.02.019","article-title":"Quantification of Both Platelet Count and Fibrinogen Concentration Using Maximal Clot Firmness of Thromboelastometry During Liver Transplantation","volume":"47","author":"Jeong","year":"2015","journal-title":"Transpl. Proc."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1016\/j.transproceed.2010.05.144","article-title":"Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: Randomized clinical trial","volume":"42","author":"Wang","year":"2010","journal-title":"Transpl. Proc."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1002\/hep.28148","article-title":"Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial","volume":"63","author":"Bianchini","year":"2016","journal-title":"Hepatology"},{"key":"ref_89","first-page":"19","article-title":"The use of thromboelastometry in the assessment of hemostasis during orthotopic liver transplantation reduces the demand for blood products","volume":"15","author":"Trzebicki","year":"2010","journal-title":"Ann. Transpl."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"342","DOI":"10.12659\/AOT.893741","article-title":"FIBTEM of Thromboelastometry does not Accurately Represent Fibrinogen Concentration in Patients with Severe Hypofibrinogenemia During Liver Transplantation","volume":"20","author":"Seo","year":"2015","journal-title":"Ann. Transpl."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1097\/EJA.0000000000000322","article-title":"Assessment of haemostasis in patients with cirrhosis: Relevance of the ROTEM tests?: A prospective, cross-sectional study","volume":"33","author":"Lentschener","year":"2016","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3343\/alm.2017.37.3.204","article-title":"Thromboelastographic Evaluation of Coagulation in Patients With Liver Disease","volume":"37","author":"Shin","year":"2017","journal-title":"Ann. Lab. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1111\/jth.12706","article-title":"Cirrhosis patients have a coagulopathy that is associated with decreased clot formation capacity","volume":"12","author":"Kleinegris","year":"2014","journal-title":"J. Thromb. Haemost."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/rth2.12037","article-title":"Thromboelastography does not predict outcome in different etiologies of cirrhosis","volume":"1","author":"Hugenholtz","year":"2017","journal-title":"Res. Pr. Thromb. Haemost."},{"key":"ref_95","first-page":"513","article-title":"Potential applications of thromboelastography in patients with acute and chronic liver disease","volume":"8","author":"Stravitz","year":"2012","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1111\/jth.14751","article-title":"Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay","volume":"18","author":"Wan","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1111\/j.1538-7933.2004.00618.x","article-title":"Initiating and potentiating role of platelets in tissue factor-induced thrombin generation in the presence of plasma: Subject-dependent variation in thrombogram characteristics","volume":"2","author":"Vanschoonbeek","year":"2004","journal-title":"J. Thromb. Haemost."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1182\/blood-2016-10-746479","article-title":"Elevated hematocrit enhances platelet accumulation following vascular injury","volume":"129","author":"Walton","year":"2017","journal-title":"Blood"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1038\/ncomms5257","article-title":"Identification of platelet function defects by multi-parameter assessment of thrombus formation","volume":"5","author":"Swieringa","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.3324\/haematol.2018.198853","article-title":"High-throughput elucidation of thrombus formation reveals sources of platelet function variability","volume":"104","author":"Brouns","year":"2019","journal-title":"Haematologica"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/9\/3294\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:26:02Z","timestamp":1760174762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/9\/3294"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,6]]},"references-count":100,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["ijms21093294"],"URL":"https:\/\/doi.org\/10.3390\/ijms21093294","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,6]]}}}