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• W2003236415 abstract "The recent debate on abnormal hemostasis tests and bleeding in chronic liver disease that appeared in the recent issue of the Journal [1Reverter J.C. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? Yes.J Thromb Haemost. 2006; 4: 717-20Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 2Mannucci P.M. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? No.J Thromb Haemost. 2006; 4: 721-3Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar] leaves room for further discussion. The hypothesis that the time‐honored prothrombin time (PT) and activated partial thromboplastin time (APTT) tests are unfit to reflect the coagulopathy associated with cirrhosis [3Tripodi A. Salerno F. Chantarangkul V. Clerici M. Cazzaniga M. Primignani M. Mannuccio Mannucci P. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests.Hepatology. 2005; 41: 553-8Crossref PubMed Scopus (530) Google Scholar] may be well applied to other acquired coagulopathies when both the pro‐ and anticoagulants are decreased to a similar extent. However, it does not apply to oral anticoagulant treatment as suggested by Reverter [1Reverter J.C. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? Yes.J Thromb Haemost. 2006; 4: 717-20Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar]. In patients on oral anticoagulants, there is a considerable decrease of pro‐coagulant factors; however this is not accompanied by a parallel decrease of the anti‐coagulant drive. Indeed, antithrombin [4De Stefano V. Leone G. De Martini D. Di Donfrancesco A. Accorra F. Bizzi B. Effect of oral anticoagulant treatment on plasma and serum antithrombin III: a study on 172 patients at different levels of anticoagulation.Haemostasis. 1987; 17: 195-200Google Scholar] and possibly tissue factor pathway inhibitor (the other two most important anticoagulant mechanisms operating in vivo together with the protein C pathway) are not decreased and this should be taken into account when considering the suitability of PT in monitoring the safety and efficacy of oral anticoagulant treatment. Another important issue raised by Reverter [1Reverter J.C. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? Yes.J Thromb Haemost. 2006; 4: 717-20Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar] is the application of the PT results as one of the parameters to calculate such prognostic indexes as Child‐Pugh [5Pugh R.N. Murray‐Lyon I.M. Dawson J.L. Pietroni M.C. Williams R. Transection of the oesophagus for bleeding oesophageal varices.Br J Surg. 1973; 60: 646-9Crossref PubMed Scopus (6843) Google Scholar] and MELD [6Forman L.M. Lucey M.R. Predicting the prognosis of chronic liver disease: an evolution from child to MELD. Mayo end‐stage liver disease.Hepatology. 2001; 33: 473-5Crossref PubMed Scopus (191) Google Scholar] scores. While the PT test per se is a reliable index of liver function, the use of the International Normalized Ratio (INR) scale might be ineffective in harmonizing the results in patients with liver disease. Studies published over the years indicate that indiscriminate use of the INR scale in this context may enhance rather than minimize between‐laboratory differences [7Robert A. Chazouilleres O. Prothrombin time in liver failure: time, ratio, activity percentage, or international normalized ratio.Hepatology. 1996; 24: 1392-4Crossref PubMed Google Scholar, 8Trotter J.F. Brimhall B. Arjal R. Phillips C. Specific laboratory methodologies achieve higher model for endstage liver disease (MELD) scores for patients listed for liver transplantation.Liver Transpl. 2004; 10: 995-1000Crossref PubMed Scopus (151) Google Scholar]. The international sensitivity index (ISI) of commercial thromboplastins used to convert PT results into the INR scale is obtained by testing plasmas from healthy subjects and patients stabilized on oral anticoagulants [9Tripodi A. Breukink‐Engbers W.G. Van Den Besselaar A.M. Oral anticoagulant monitoring by laboratory or near‐patient testing: what a clinician should be aware of.Semin Vasc Med. 2003; 3: 243-54Crossref PubMed Scopus (15) Google Scholar]. Therefore, it is not surprising that this scale fails to harmonize results in patients with liver disease where the coagulopathy is qualitatively different from that induced by oral anticoagulants. In addition to the well‐known defects of the vitamin K dependent coagulation factors also factor (F) V and fibrinogen are variably decreased in patients with liver disease, but not in patients on oral anticoagulants. It has been shown that a partial deficiency of FV may have important consequences for the harmonization of results even in patients on oral anticoagulant treatment [10Tripodi A. Chantarangkul V. Akkawat B. Clerici M. Mannucci P.M. A partial factor V deficiency in anticoagulated lyophilized plasmas has been identified as a cause of the international normalized ratio discrepancy in the external quality assessment scheme.Thromb Res. 1995; 78: 283-92Abstract Full Text PDF PubMed Scopus (30) Google Scholar]. The use of combined reagents (i.e. brain extracts supplemented with adsorbed bovine plasma to optimize the concentrations of fibrinogen and FV) might resolve the problem of the partial deficiency of these two coagulation factors in liver disease, but it is unlikely to resolve the issue of harmonization of results. The degree of failure for the INR to harmonize results in patients with liver disease is presumably dependent on the combination of reagent/coagulometer used for testing and is therefore unpredictable. If the intended use of the MELD score is to prioritize patients for liver transplantation then there is an urgent need to reinvestigate this issue and develop alternative results expression for the PT or alternative indexes to be used in the MELD score. The authors state that they have no conflict of interest." @default.
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• W2003236415 title "Hemostasis in chronic liver disease" @default.
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