{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T07:07:53Z","timestamp":1770275273195,"version":"3.49.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1888,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Patients with cirrhosis possess an imbalance in procoagulant versus anticoagulant activity due to increased factor VIII and decreased protein C. This imbalance can be detected by thrombin-generation assays performed in the presence\/absence of thrombomodulin (predicate assay) that are not readily available in clinical laboratories. We sought to assess this hypercoagulability with a simpler thrombin-generation assay performed in the presence\/absence of Protac, a snake venom that activates protein C in a manner similar to thrombomodulin (new assay). We analyzed blood from 105 patients with cirrhosis and 105 healthy subjects (controls). Results for the predicate-assay or the new-assay were expressed as ratio (with:without thrombomodulin) or as Protac-induced coagulation inhibition (PICI%). By definition, high ratios or low PICI% translate into hypercoagulability. The median(range) PICI% was lower in patients (74% [31%-97%]) than controls (93% [72%-99%];<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.001), indicating that patients with cirrhosis are resistant to the action of Protac. This resistance resulted in greater plasma hypercoagulability in patients who were Child class C than those who were A or B. The hypercoagulability of Child C cirrhosis (63% [31%-92%]) was similar to that observed for patients with factor V Leiden (69% [15%-80%];<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.59). The PICI% values were correlated with the levels of protein C (rho = 0.728,<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.001) or factor VIII (rho = \u22120.517,<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.001). Finally, the PICI% values were correlated with the predicate assay (rho = \u22120.580,<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.001).<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>\n                                 <jats:bold>The hypercoagulability of plasma from patients with cirrhosis can be detected with the new assay, which compares favorably with the other markers of hypercoagulability (i.e., high factor VIII and low protein C) and with the predicate-assay based on thrombin-generation with\/without thrombomodulin. Advantages of the new assay over the predicate assay are easy performance and standardized results. Prospective trials are needed to ascertain whether it is useful to predict thrombosis in patients with cirrhosis. Hepatology 2010<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.23653","type":"journal-article","created":{"date-parts":[[2010,3,8]],"date-time":"2010-03-08T13:58:03Z","timestamp":1268056683000},"page":"249-255","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":115,"title":["Detection of the Imbalance of Procoagulant Versus Anticoagulant Factors in Cirrhosis by a Simple Laboratory Method"],"prefix":"10.1097","volume":"52","author":[{"given":"Armando","family":"Tripodi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Primignani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Lemma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veena","family":"Chantarangkul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Dell'Era","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Iannuzzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Aghemo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Mannuccio","family":"Mannucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R2-27-20250312","doi-asserted-by":"crossref","first-page":"553558","DOI":"10.1002\/hep.20569","article-title":"Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests.","volume":"41","author":"Tripodi","year":"2005","journal-title":"Hepatology"},{"key":"R3-27-20250312","doi-asserted-by":"crossref","first-page":"440445","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":"R4-27-20250312","doi-asserted-by":"crossref","first-page":"727733","DOI":"10.1016\/j.jhep.2007.01.015","article-title":"Abnormalities of hemostasis in chronic liver disease. reappraisal of their clinical significance and need for clinical and laboratory research.","volume":"46","author":"Tripodi","year":"2007","journal-title":"J Hepatol"},{"key":"R5-27-20250312","doi-asserted-by":"crossref","first-page":"21052111","DOI":"10.1053\/j.gastro.2009.08.045","article-title":"An imbalance of pro vs anticoagulation factors in plasma from patients with cirrhosis.","volume":"137","author":"Tripodi","year":"2009","journal-title":"Gastroenterology"},{"key":"R6-27-20250312","doi-asserted-by":"crossref","first-page":"15241528","DOI":"10.1111\/j.1572-0241.2006.00588.x","article-title":"Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism.","volume":"101","author":"Northup","year":"2006","journal-title":"Am J Gastroenterol"},{"key":"R7-27-20250312","first-page":"96101","article-title":"Risk of venous thromboembolism in patients with liver disease: a nationwide populationbased casecontrol study.","volume":"104","author":"Sgaard","year":"2009","journal-title":"Am J Gastroenterol"},{"key":"R8-27-20250312","doi-asserted-by":"crossref","first-page":"13841393","DOI":"10.1002\/hep.22192","article-title":"Thrombosis and anticoagulation in liver disease.","volume":"47","author":"Valla","year":"2008","journal-title":"Hepatology"},{"key":"R9-27-20250312","doi-asserted-by":"crossref","first-page":"279286","DOI":"10.1016\/0016-5085(85)90327-0","article-title":"Incidence of portal vein thrombosis in liver cirrhosis. An angiographic study in 708 patients.","volume":"89","author":"Okuda","year":"1985","journal-title":"Gastroenterology"},{"key":"R10-27-20250312","doi-asserted-by":"crossref","first-page":"691697","DOI":"10.1136\/gut.2004.042796","article-title":"Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation.","volume":"54","author":"Francoz","year":"2005","journal-title":"Gut"},{"key":"R11-27-20250312","doi-asserted-by":"crossref","first-page":"646649","DOI":"10.1002\/bjs.1800600817","article-title":"Transaction of the oesophagus for bleeding oesophageal varices.","volume":"60","author":"Pugh","year":"1973","journal-title":"Br J Surg"},{"key":"R12-27-20250312","doi-asserted-by":"crossref","first-page":"137143","DOI":"10.1016\/j.thromres.2008.11.017","article-title":"A new chromogenic assay (HemosIL ThromboPath) is sensitive to major prothrombotic risk factors affecting the protein C pathway. Results of a multicenter study.","volume":"124","author":"Toulon","year":"2009","journal-title":"Thromb Res"},{"key":"R13-27-20250312","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1159\/000071636","article-title":"Calibrated automated thrombin generation measurement in clotting plasma.","volume":"33","author":"Hemker","year":"2003","journal-title":"Pathophysiol Haemost Thromb"},{"key":"R14-27-20250312","first-page":"547554","article-title":"Thrombin generation assessed as endogenous thrombin potential (ETP) in patients with hypo or hypercoagulability. Effects of phospholipids, tissue factor and residual platelets on the measurement performed in plateletpoor and plateletrich plasma.","volume":"88","author":"Chantarangkul","year":"2003","journal-title":"Haematologica"},{"key":"R15-27-20250312","first-page":"716","article-title":"Blood coagulation dynamics in haemostasis.","volume":"29","author":"Mann","year":"2009","journal-title":"Hamostaseologie"},{"key":"R16-27-20250312","doi-asserted-by":"crossref","first-page":"109116","DOI":"10.1532\/IJH97.03149","article-title":"Progress in the understanding of the protein C anticoagulant pathway.","volume":"79","author":"Dahlback","year":"2004","journal-title":"Int J Hematol"},{"key":"R17-27-20250312","doi-asserted-by":"crossref","first-page":"267275","DOI":"10.1160\/TH03-05-0310","article-title":"Factor VIII expression in liver disease.","volume":"91","author":"Hollestelle","year":"2004","journal-title":"Thromb Haemost"},{"key":"R18-27-20250312","doi-asserted-by":"crossref","first-page":"352356","DOI":"10.1080\/13651820701599033","article-title":"Liver transplantation in adult patients with portal vein thrombosis: risk factors, management and outcome.","volume":"9","author":"Lendoire","year":"2007","journal-title":"HPB (Oxford)"},{"key":"R19-27-20250312","doi-asserted-by":"crossref","first-page":"18731881","DOI":"10.1097\/00007890-200005150-00023","article-title":"Portal vein thrombosis in adults undergoing liver transplantation: risk factors, screening, management, and outcome.","volume":"69","author":"Yerdel","year":"2000","journal-title":"Transplantation"},{"key":"R20-27-20250312","doi-asserted-by":"crossref","first-page":"716721","DOI":"10.1111\/j.1399-0012.2007.00728.x","article-title":"Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality.","volume":"21","author":"Llado","year":"2007","journal-title":"Clin Transplant"},{"key":"R21-27-20250312","doi-asserted-by":"crossref","first-page":"327335","DOI":"10.1097\/00001721-199709000-00002","article-title":"A Protacbased screening test for activated protein Cresistant factor Va and other defects of the protein C anticoagulant pathway.","volume":"8","author":"Gable","year":"1997","journal-title":"Blood Coagul Fibrinolysis"},{"key":"R22-27-20250312","doi-asserted-by":"crossref","first-page":"6467","DOI":"10.1038\/369064a0","article-title":"Mutation in blood coagulation factor V associated with resistance to activated protein C.","volume":"369","author":"Bertina","year":"1994","journal-title":"Nature"},{"key":"R23-27-20250312","doi-asserted-by":"crossref","first-page":"25212524","DOI":"10.1172\/JCI117623","article-title":"Identification of the same factor V gene mutation in 47 out of 50 thrombosisprone families with inherited resistance to activated protein C.","volume":"94","author":"Zoller","year":"1994","journal-title":"J Clin Invest"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.23653","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201007000-00027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T11:02:54Z","timestamp":1741777374000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201007000-00027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.23653","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2010,7]]}}}