Effectiveness of venous thromboembolism prophylaxis in patients with liver disease
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摘要
BACKGROUND Patients with liver disease are concomitantly at increased risk of venous thromboembolism(VTE) and bleeding events due to changes in the balance of pro-and anti-hemostatic substances. As such, recommendations for the use of pharmacological VTE prophylaxis are lacking. Recent studies have found no difference in rates of VTE in those receiving and not receiving pharmacological VTE prophylaxis, though most studies have been small. Thus, our study sought to establish if pharmacological VTE prophylaxis is effective and safe in patients with liver disease.AIM To determine if there is net clinical benefit to providing pharmacological VTE prophylaxis to cirrhotic patients.METHODS In this retrospective study, 1806 patients were propensity matched to assess if pharmacological VTE prophylaxis is effective and safe in patients with cirrhosis.Patients were divided and evaluated based on receipt of pharmacological VTE prophylaxis.RESULTS The composite primary outcome of VTE or major bleeding was more common in the no prophylaxis group than the prophylaxis group(8.7% vs 5.1%, P = 0.002),though this outcome was driven by higher rates of major bleeding(6.9% vs 2.9%,P < 0.001) rather than VTE(1.9% vs 2.2%, P = 0.62). There was no difference inlength of stay or in-hospital mortality between groups. Pharmacological VTE prophylaxis was independently associated with lower rates of major bleeding(OR = 0.42, 95%CI: 0.25-0.68, P = 0.0005), but was not protective against VTE on multivariable analysis.CONCLUSION Pharmacological VTE prophylaxis was not associated with a significant reduction in the rate of VTE in patients with liver disease, though no increase in major bleeding events was observed.
BACKGROUND Patients with liver disease are concomitantly at increased risk of venous thromboembolism(VTE) and bleeding events due to changes in the balance of pro-and anti-hemostatic substances. As such, recommendations for the use of pharmacological VTE prophylaxis are lacking. Recent studies have found no difference in rates of VTE in those receiving and not receiving pharmacological VTE prophylaxis, though most studies have been small. Thus, our study sought to establish if pharmacological VTE prophylaxis is effective and safe in patients with liver disease.AIM To determine if there is net clinical benefit to providing pharmacological VTE prophylaxis to cirrhotic patients.METHODS In this retrospective study, 1806 patients were propensity matched to assess if pharmacological VTE prophylaxis is effective and safe in patients with cirrhosis.Patients were divided and evaluated based on receipt of pharmacological VTE prophylaxis.RESULTS The composite primary outcome of VTE or major bleeding was more common in the no prophylaxis group than the prophylaxis group(8.7% vs 5.1%, P = 0.002),though this outcome was driven by higher rates of major bleeding(6.9% vs 2.9%,P < 0.001) rather than VTE(1.9% vs 2.2%, P = 0.62). There was no difference inlength of stay or in-hospital mortality between groups. Pharmacological VTE prophylaxis was independently associated with lower rates of major bleeding(OR = 0.42, 95%CI: 0.25-0.68, P = 0.0005), but was not protective against VTE on multivariable analysis.CONCLUSION Pharmacological VTE prophylaxis was not associated with a significant reduction in the rate of VTE in patients with liver disease, though no increase in major bleeding events was observed.
BACKGROUND Patients with liver disease are concomitantly at increased risk of venous thromboembolism(VTE) and bleeding events due to changes in the balance of pro-and anti-hemostatic substances. As such, recommendations for the use of pharmacological VTE prophylaxis are lacking. Recent studies have found no difference in rates of VTE in those receiving and not receiving pharmacological VTE prophylaxis, though most studies have been small. Thus, our study sought to establish if pharmacological VTE prophylaxis is effective and safe in patients with liver disease.AIM To determine if there is net clinical benefit to providing pharmacological VTE prophylaxis to cirrhotic patients.METHODS In this retrospective study, 1806 patients were propensity matched to assess if pharmacological VTE prophylaxis is effective and safe in patients with cirrhosis.Patients were divided and evaluated based on receipt of pharmacological VTE prophylaxis.RESULTS The composite primary outcome of VTE or major bleeding was more common in the no prophylaxis group than the prophylaxis group(8.7% vs 5.1%, P = 0.002),though this outcome was driven by higher rates of major bleeding(6.9% vs 2.9%,P < 0.001) rather than VTE(1.9% vs 2.2%, P = 0.62). There was no difference inlength of stay or in-hospital mortality between groups. Pharmacological VTE prophylaxis was independently associated with lower rates of major bleeding(OR = 0.42, 95%CI: 0.25-0.68, P = 0.0005), but was not protective against VTE on multivariable analysis.CONCLUSION Pharmacological VTE prophylaxis was not associated with a significant reduction in the rate of VTE in patients with liver disease, though no increase in major bleeding events was observed.
引文
1 Tripodi A,Mannucci PM.The coagulopathy of chronic liver disease.N Engl J Med 2011;365:147-156[PMID:21751907 DOI:10.1056/NEJMra1011170]
2 Heit JA,Silverstein MD,Mohr DN,Petterson TM,O'Fallon WM,Melton LJ.Risk factors for deep vein thrombosis and pulmonary embolism:a population-based case-control study.Arch Intern Med 2000;160:809-815[PMID:10737280]
3 Ali M,Ananthakrishnan AN,McGinley EL,Saeian K.Deep vein thrombosis and pulmonary embolism in hospitalized patients with cirrhosis:a nationwide analysis.Dig Dis Sci 2011;56:2152-2159[PMID:21279685 DOI:10.1007/s10620-011-1582-5]
4 Northup PG,McMahon MM,Ruhl AP,Altschuler SE,Volk-Bednarz A,Caldwell SH,Berg CL.Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism.Am J Gastroenterol 2006;101:1524-1528;quiz 1680[PMID:16863556 DOI:10.1111/j.1572-0241.2006.00588.x]
5 Gulley D,Teal E,Suvannasankha A,Chalasani N,Liangpunsakul S.Deep vein thrombosis and pulmonary embolism in cirrhosis patients.Dig Dis Sci 2008;53:3012-3017[PMID:18443906 DOI:10.1007/s10620-008-0265-3]
6 Aldawood A,Arabi Y,Aljumah A,Alsaadi A,Rishu A,Aldorzi H,Alqahtani S,Alsultan M,Felemban A.The incidence of venous thromboembolism and practice of deep venous thrombosis prophylaxis in hospitalized cirrhotic patients.Thromb J 2011;9:1[PMID:21244669 DOI:10.1186/1477-9560-9-1]
7 Dabbagh O,Oza A,Prakash S,Sunna R,Saettele TM.Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease.Chest 2010;137:1145-1149[PMID:20040609 DOI:10.1378/chest.09-2177]
8 S?gaard KK,Horváth-PuhóE,Gr?nbaek H,Jepsen P,Vilstrup H,S?rensen HT.Risk of venous thromboembolism in patients with liver disease:a nationwide population-based case-control study.Am JGastroenterol 2009;104:96-101[PMID:19098856 DOI:10.1038/ajg.2008.34]
9 Bogari H,Patanwala AE,Cosgrove R,Katz M.Risk-assessment and pharmacological prophylaxis of venous thromboembolism in hospitalized patients with chronic liver disease.Thromb Res 2014;134:1220-1223[PMID:25294587 DOI:10.1016/j.thromres.2014.09.031]
10 Smith CB,Hurdle AC,Kemp LO,Sands C,Twilla JD.Evaluation of venous thromboembolism prophylaxis in patients with chronic liver disease.J Hosp Med 2013;8:569-573[PMID:24101541 DOI:10.1002/jhm.2086]
11 Moorehead KJ,Jeffres MN,Mueller SW.A Retrospective Cohort Analysis of Pharmacologic VTEProphylaxis and Padua Prediction Score in Hospitalized Patients With Chronic Liver Disease.J Pharm Pract 2017;30:58-63[PMID:26475125 DOI:10.1177/0897190015611570]
12 Shatzel J,Dulai PS,Harbin D,Cheung H,Reid TN,Kim J,James SL,Khine H,Batman S,Whyman J,Dickson RC,Ornstein DL.Safety and efficacy of pharmacological thromboprophylaxis for hospitalized patients with cirrhosis:a single-center retrospective cohort study.J Thromb Haemost 2015;13:1245-1253[PMID:25955079 DOI:10.1111/jth.13000]
13 S?gaard KK,Horváth-PuhóE,Montomoli J,Vilstrup H,S?rensen HT.Cirrhosis is Associated with an Increased 30-Day Mortality After Venous Thromboembolism.Clin Transl Gastroenterol 2015;6:e97[PMID:26133110 DOI:10.1038/ctg.2015.27]
14 Schulman S,Kearon C;Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.J Thromb Haemost2005;3:692-694[PMID:15842354 DOI:10.1111/j.1538-7836.2005.01204.x]
15 Tripodi A,Primignani M,Chantarangkul V,Dell'Era A,Clerici M,de Franchis R,Colombo M,Mannucci PM.An imbalance of pro-vs anti-coagulation factors in plasma from patients with cirrhosis.Gastroenterology 2009;137:2105-2111[PMID:19706293 DOI:10.1053/j.gastro.2009.08.045]
16 Tripodi A,Primignani M,Chantarangkul V,Clerici M,Dell'Era A,Fabris F,Salerno F,Mannucci PM.Thrombin generation in patients with cirrhosis:the role of platelets.Hepatology 2006;44:440-445[PMID:16871542 DOI:10.1002/hep.21266]
17 Lisman T,Porte RJ.Rebalanced hemostasis in patients with liver disease:evidence and clinical consequences.Blood 2010;116:878-885[PMID:20400681 DOI:10.1182/blood-2010-02-261891]
18 Gatt A,Riddell A,Calvaruso V,Tuddenham EG,Makris M,Burroughs AK.Enhanced thrombin generation in patients with cirrhosis-induced coagulopathy.J Thromb Haemost 2010;8:1994-2000[PMID:20546119 DOI:10.1111/j.1538-7836.2010.03937.x]
19 Potze W,Arshad F,Adelmeijer J,Blokzijl H,van den Berg AP,Porte RJ,Lisman T.Routine coagulation assays underestimate levels of antithrombin-dependent drugs but not of direct anticoagulant drugs in plasma from patients with cirrhosis.Br J Haematol 2013;163:666-673[PMID:24219333 DOI:10.1111/bjh.12593]
20 Potze W,Arshad F,Adelmeijer J,Blokzijl H,van den Berg AP,Meijers JC,Porte RJ,Lisman T.Differential in vitro inhibition of thrombin generation by anticoagulant drugs in plasma from patients with cirrhosis.PLoS One 2014;9:e88390[PMID:24505487 DOI:10.1371/journal.pone.0088390]
21 Northup PG.Hypercoagulation in liver disease.Clin Liver Dis 2009;13:109-116[PMID:19150315DOI:10.1016/j.cld.2008.09.003]
22 Tripodi 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;41:553-558[PMID:15726661 DOI:10.1002/hep.20569]
23 Kearon C,Akl EA,Comerota AJ,Prandoni P,Bounameaux H,Goldhaber SZ,Nelson ME,Wells PS,Gould MK,Dentali F,Crowther M,Kahn SR.Antithrombotic therapy for VTE disease:Antithrombotic Therapy and Prevention of Thrombosis,9th ed:American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Chest 2012;141:e419S-e496S[PMID:22315268 DOI:10.1378/chest.11-2301]
24 Wu H,Nguyen GC.Liver cirrhosis is associated with venous thromboembolism among hospitalized patients in a nationwide US study.Clin Gastroenterol Hepatol 2010;8:800-805[PMID:20566312 DOI:10.1016/j.cgh.2010.05.014]
25 Gómez Cuervo C,Bisbal Pardo O,Pérez-Jacoiste Asín MA.Efficacy and safety of the use of heparin as thromboprophylaxis in patients with liver cirrhosis:a systematic review and meta-analysis.Thromb Res2013;132:414-419[PMID:23993900 DOI:10.1016/j.thromres.2013.08.001]
26 Myers RP,Shaheen AA,Faris P,Aspinall AI,Burak KW.Revision of MELD to include serum albumin improves prediction of mortality on the liver transplant waiting list.PLoS One 2013;8:e51926[PMID:23349678 DOI:10.1371/journal.pone.0051926]
27 Myers RP,Shaheen AA,Aspinall AI,Quinn RR,Burak KW.Gender,renal function,and outcomes on the liver transplant waiting list:assessment of revised MELD including estimated glomerular filtration rate.JHepatol 2011;54:462-470[PMID:21109324 DOI:10.1016/j.jhep.2010.07.015]
28 Zoli M,Cordiani MR,Marchesini G,Iervese T,Labate AM,Bonazzi C,Bianchi G,Pisi E.Prognostic indicators in compensated cirrhosis.Am J Gastroenterol 1991;86:1508-1513[PMID:1928047]
29 Merkel C,Bolognesi M,Angeli P,Noventa F,Caregaro L,Sacerdoti D,Gatta A.Prognostic indicators of survival in patients with cirrhosis and esophageal varices,without previous bleeding.Am J Gastroenterol1989;84:717-722[PMID:2787099]
30 Realdi G,Fattovich G,Hadziyannis S,Schalm SW,Almasio P,Sanchez-Tapias J,Christensen E,Giustina G,Noventa F.Survival and prognostic factors in 366 patients with compensated cirrhosis type B:a multicenter study.The Investigators of the European Concerted Action on Viral Hepatitis(EUROHEP).JHepatol 1994;21:656-666[PMID:7814813]
31 Assy N,Bekirov I,Mejritsky Y,Solomon L,Szvalb S,Hussein O.Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases.World J Gastroenterol2005;11:5834-5839[PMID:16270394]
32 Papatheodoridis GV,Chrysanthos N,Cholongitas E,Pavlou E,Apergis G,Tiniakos DG,Andrioti E,Theodossiades G,Archimandritis AJ.Thrombotic risk factors and liver histologic lesions in non-alcoholic fatty liver disease.J Hepatol 2009;51:931-938[PMID:19726097 DOI:10.1016/j.jhep.2009.06.023]
33 Ben-Ari Z,Panagou M,Patch D,Bates S,Osman E,Pasi J,Burroughs A.Hypercoagulability in patients with primary biliary cirrhosis and primary sclerosing cholangitis evaluated by thrombelastography.JHepatol 1997;26:554-559[PMID:9075662]
34 Saleh T,Matta F,Alali F,Stein PD.Venous thromboembolism with chronic liver disease.Am J Med2011;124:64-68[PMID:21187186 DOI:10.1016/j.amjmed.2010.08.014]
35 Mangia A,Margaglione M,Cascavilla I,Gentile R,Cappucci G,Facciorusso D,Grandone E,Di Minno G,Rizzetto M,Andriulli A.Anticardiolipin antibodies in patients with liver disease.Am J Gastroenterol1999;94:2983-2987[PMID:10520856 DOI:10.1111/j.1572-0241.1999.01447.x]
36 Prieto J,Yuste JR,Beloqui O,Civeira MP,Riezu JI,Aguirre B,Sangro B.Anticardiolipin antibodies in chronic hepatitis C:implication of hepatitis C virus as the cause of the antiphospholipid syndrome.Hepatology 1996;23:199-204[PMID:8591841 DOI:10.1002/hep.510230201]
37 Di Minno MN,Tufano A,Rusolillo A,Di Minno G,Tarantino G.High prevalence of nonalcoholic fatty liver in patients with idiopathic venous thromboembolism.World J Gastroenterol 2010;16:6119-6122[PMID:21182227]
38 Barbar S,Noventa F,Rossetto V,Ferrari A,Brandolin B,Perlati M,De Bon E,Tormene D,Pagnan A,Prandoni P.A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism:the Padua Prediction Score.J Thromb Haemost 2010;8:2450-2457[PMID:20738765 DOI:10.1111/j.1538-7836.2010.04044.x]
39 Caprini JA,Arcelus JI,Reyna JJ.Effective risk stratification of surgical and nonsurgical patients for venous thromboembolic disease.Semin Hematol 2001;38:12-19[PMID:11449339]
2 Heit JA,Silverstein MD,Mohr DN,Petterson TM,O'Fallon WM,Melton LJ.Risk factors for deep vein thrombosis and pulmonary embolism:a population-based case-control study.Arch Intern Med 2000;160:809-815[PMID:10737280]
3 Ali M,Ananthakrishnan AN,McGinley EL,Saeian K.Deep vein thrombosis and pulmonary embolism in hospitalized patients with cirrhosis:a nationwide analysis.Dig Dis Sci 2011;56:2152-2159[PMID:21279685 DOI:10.1007/s10620-011-1582-5]
4 Northup PG,McMahon MM,Ruhl AP,Altschuler SE,Volk-Bednarz A,Caldwell SH,Berg CL.Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism.Am J Gastroenterol 2006;101:1524-1528;quiz 1680[PMID:16863556 DOI:10.1111/j.1572-0241.2006.00588.x]
5 Gulley D,Teal E,Suvannasankha A,Chalasani N,Liangpunsakul S.Deep vein thrombosis and pulmonary embolism in cirrhosis patients.Dig Dis Sci 2008;53:3012-3017[PMID:18443906 DOI:10.1007/s10620-008-0265-3]
6 Aldawood A,Arabi Y,Aljumah A,Alsaadi A,Rishu A,Aldorzi H,Alqahtani S,Alsultan M,Felemban A.The incidence of venous thromboembolism and practice of deep venous thrombosis prophylaxis in hospitalized cirrhotic patients.Thromb J 2011;9:1[PMID:21244669 DOI:10.1186/1477-9560-9-1]
7 Dabbagh O,Oza A,Prakash S,Sunna R,Saettele TM.Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease.Chest 2010;137:1145-1149[PMID:20040609 DOI:10.1378/chest.09-2177]
8 S?gaard KK,Horváth-PuhóE,Gr?nbaek H,Jepsen P,Vilstrup H,S?rensen HT.Risk of venous thromboembolism in patients with liver disease:a nationwide population-based case-control study.Am JGastroenterol 2009;104:96-101[PMID:19098856 DOI:10.1038/ajg.2008.34]
9 Bogari H,Patanwala AE,Cosgrove R,Katz M.Risk-assessment and pharmacological prophylaxis of venous thromboembolism in hospitalized patients with chronic liver disease.Thromb Res 2014;134:1220-1223[PMID:25294587 DOI:10.1016/j.thromres.2014.09.031]
10 Smith CB,Hurdle AC,Kemp LO,Sands C,Twilla JD.Evaluation of venous thromboembolism prophylaxis in patients with chronic liver disease.J Hosp Med 2013;8:569-573[PMID:24101541 DOI:10.1002/jhm.2086]
11 Moorehead KJ,Jeffres MN,Mueller SW.A Retrospective Cohort Analysis of Pharmacologic VTEProphylaxis and Padua Prediction Score in Hospitalized Patients With Chronic Liver Disease.J Pharm Pract 2017;30:58-63[PMID:26475125 DOI:10.1177/0897190015611570]
12 Shatzel J,Dulai PS,Harbin D,Cheung H,Reid TN,Kim J,James SL,Khine H,Batman S,Whyman J,Dickson RC,Ornstein DL.Safety and efficacy of pharmacological thromboprophylaxis for hospitalized patients with cirrhosis:a single-center retrospective cohort study.J Thromb Haemost 2015;13:1245-1253[PMID:25955079 DOI:10.1111/jth.13000]
13 S?gaard KK,Horváth-PuhóE,Montomoli J,Vilstrup H,S?rensen HT.Cirrhosis is Associated with an Increased 30-Day Mortality After Venous Thromboembolism.Clin Transl Gastroenterol 2015;6:e97[PMID:26133110 DOI:10.1038/ctg.2015.27]
14 Schulman S,Kearon C;Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.J Thromb Haemost2005;3:692-694[PMID:15842354 DOI:10.1111/j.1538-7836.2005.01204.x]
15 Tripodi A,Primignani M,Chantarangkul V,Dell'Era A,Clerici M,de Franchis R,Colombo M,Mannucci PM.An imbalance of pro-vs anti-coagulation factors in plasma from patients with cirrhosis.Gastroenterology 2009;137:2105-2111[PMID:19706293 DOI:10.1053/j.gastro.2009.08.045]
16 Tripodi A,Primignani M,Chantarangkul V,Clerici M,Dell'Era A,Fabris F,Salerno F,Mannucci PM.Thrombin generation in patients with cirrhosis:the role of platelets.Hepatology 2006;44:440-445[PMID:16871542 DOI:10.1002/hep.21266]
17 Lisman T,Porte RJ.Rebalanced hemostasis in patients with liver disease:evidence and clinical consequences.Blood 2010;116:878-885[PMID:20400681 DOI:10.1182/blood-2010-02-261891]
18 Gatt A,Riddell A,Calvaruso V,Tuddenham EG,Makris M,Burroughs AK.Enhanced thrombin generation in patients with cirrhosis-induced coagulopathy.J Thromb Haemost 2010;8:1994-2000[PMID:20546119 DOI:10.1111/j.1538-7836.2010.03937.x]
19 Potze W,Arshad F,Adelmeijer J,Blokzijl H,van den Berg AP,Porte RJ,Lisman T.Routine coagulation assays underestimate levels of antithrombin-dependent drugs but not of direct anticoagulant drugs in plasma from patients with cirrhosis.Br J Haematol 2013;163:666-673[PMID:24219333 DOI:10.1111/bjh.12593]
20 Potze W,Arshad F,Adelmeijer J,Blokzijl H,van den Berg AP,Meijers JC,Porte RJ,Lisman T.Differential in vitro inhibition of thrombin generation by anticoagulant drugs in plasma from patients with cirrhosis.PLoS One 2014;9:e88390[PMID:24505487 DOI:10.1371/journal.pone.0088390]
21 Northup PG.Hypercoagulation in liver disease.Clin Liver Dis 2009;13:109-116[PMID:19150315DOI:10.1016/j.cld.2008.09.003]
22 Tripodi 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;41:553-558[PMID:15726661 DOI:10.1002/hep.20569]
23 Kearon C,Akl EA,Comerota AJ,Prandoni P,Bounameaux H,Goldhaber SZ,Nelson ME,Wells PS,Gould MK,Dentali F,Crowther M,Kahn SR.Antithrombotic therapy for VTE disease:Antithrombotic Therapy and Prevention of Thrombosis,9th ed:American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Chest 2012;141:e419S-e496S[PMID:22315268 DOI:10.1378/chest.11-2301]
24 Wu H,Nguyen GC.Liver cirrhosis is associated with venous thromboembolism among hospitalized patients in a nationwide US study.Clin Gastroenterol Hepatol 2010;8:800-805[PMID:20566312 DOI:10.1016/j.cgh.2010.05.014]
25 Gómez Cuervo C,Bisbal Pardo O,Pérez-Jacoiste Asín MA.Efficacy and safety of the use of heparin as thromboprophylaxis in patients with liver cirrhosis:a systematic review and meta-analysis.Thromb Res2013;132:414-419[PMID:23993900 DOI:10.1016/j.thromres.2013.08.001]
26 Myers RP,Shaheen AA,Faris P,Aspinall AI,Burak KW.Revision of MELD to include serum albumin improves prediction of mortality on the liver transplant waiting list.PLoS One 2013;8:e51926[PMID:23349678 DOI:10.1371/journal.pone.0051926]
27 Myers RP,Shaheen AA,Aspinall AI,Quinn RR,Burak KW.Gender,renal function,and outcomes on the liver transplant waiting list:assessment of revised MELD including estimated glomerular filtration rate.JHepatol 2011;54:462-470[PMID:21109324 DOI:10.1016/j.jhep.2010.07.015]
28 Zoli M,Cordiani MR,Marchesini G,Iervese T,Labate AM,Bonazzi C,Bianchi G,Pisi E.Prognostic indicators in compensated cirrhosis.Am J Gastroenterol 1991;86:1508-1513[PMID:1928047]
29 Merkel C,Bolognesi M,Angeli P,Noventa F,Caregaro L,Sacerdoti D,Gatta A.Prognostic indicators of survival in patients with cirrhosis and esophageal varices,without previous bleeding.Am J Gastroenterol1989;84:717-722[PMID:2787099]
30 Realdi G,Fattovich G,Hadziyannis S,Schalm SW,Almasio P,Sanchez-Tapias J,Christensen E,Giustina G,Noventa F.Survival and prognostic factors in 366 patients with compensated cirrhosis type B:a multicenter study.The Investigators of the European Concerted Action on Viral Hepatitis(EUROHEP).JHepatol 1994;21:656-666[PMID:7814813]
31 Assy N,Bekirov I,Mejritsky Y,Solomon L,Szvalb S,Hussein O.Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases.World J Gastroenterol2005;11:5834-5839[PMID:16270394]
32 Papatheodoridis GV,Chrysanthos N,Cholongitas E,Pavlou E,Apergis G,Tiniakos DG,Andrioti E,Theodossiades G,Archimandritis AJ.Thrombotic risk factors and liver histologic lesions in non-alcoholic fatty liver disease.J Hepatol 2009;51:931-938[PMID:19726097 DOI:10.1016/j.jhep.2009.06.023]
33 Ben-Ari Z,Panagou M,Patch D,Bates S,Osman E,Pasi J,Burroughs A.Hypercoagulability in patients with primary biliary cirrhosis and primary sclerosing cholangitis evaluated by thrombelastography.JHepatol 1997;26:554-559[PMID:9075662]
34 Saleh T,Matta F,Alali F,Stein PD.Venous thromboembolism with chronic liver disease.Am J Med2011;124:64-68[PMID:21187186 DOI:10.1016/j.amjmed.2010.08.014]
35 Mangia A,Margaglione M,Cascavilla I,Gentile R,Cappucci G,Facciorusso D,Grandone E,Di Minno G,Rizzetto M,Andriulli A.Anticardiolipin antibodies in patients with liver disease.Am J Gastroenterol1999;94:2983-2987[PMID:10520856 DOI:10.1111/j.1572-0241.1999.01447.x]
36 Prieto J,Yuste JR,Beloqui O,Civeira MP,Riezu JI,Aguirre B,Sangro B.Anticardiolipin antibodies in chronic hepatitis C:implication of hepatitis C virus as the cause of the antiphospholipid syndrome.Hepatology 1996;23:199-204[PMID:8591841 DOI:10.1002/hep.510230201]
37 Di Minno MN,Tufano A,Rusolillo A,Di Minno G,Tarantino G.High prevalence of nonalcoholic fatty liver in patients with idiopathic venous thromboembolism.World J Gastroenterol 2010;16:6119-6122[PMID:21182227]
38 Barbar S,Noventa F,Rossetto V,Ferrari A,Brandolin B,Perlati M,De Bon E,Tormene D,Pagnan A,Prandoni P.A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism:the Padua Prediction Score.J Thromb Haemost 2010;8:2450-2457[PMID:20738765 DOI:10.1111/j.1538-7836.2010.04044.x]
39 Caprini JA,Arcelus JI,Reyna JJ.Effective risk stratification of surgical and nonsurgical patients for venous thromboembolic disease.Semin Hematol 2001;38:12-19[PMID:11449339]