Advances in anticoagulant therapy for hepatocirrhosis with portal vein thrombosis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Wenlong ,  LUO Zhiqiang , OUYANG Yongpeng , WANG Fei , CHEN Boxuan

Department of Hepatobiliary, Pancreatic, and Splenic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000,P. R. China;

Corresponding author：

LUO Zhiqiang, Email: zqluo999@163.com

Keywords：

hepatocirrhosis; portal vein thrombosis; anticoagulant therapy; prevention; review

DOI：

10.7507/1007-9424.201906035

Video：

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Objective To summarize the occurrence and development of hepatocirrhosis complicated with portal vein thrombosis (PVT), and summarize the status and prospect of anticoagulant treatment.Method The literatures and guidelines on the treatment of hepatocirrhosis complicated with PVT were collected and reviewed.Results PVT was one of the most common complications in patients with hepatocirrhosis. Its pathogenesis was complicated, and the coagulation function of patients with hepatocirrhosis was poor. In addition, patients with severe complications such as esophageal and gastric varicose bleeding (EVB) were often complicated. According to the current study, the formation of PVT was mainly related to the coagulation mechanism of patients, hemorheology changes of blood vessels, and their own factors. Treatment methods included drug therapy, interventional therapy, and surgical treatment. However, there was still controversy on anticoagulant therapy for hepatocirrhosis with PVT, and there was no complete consensus on anticoagulant indications, drug selection, course of treatment, and safety monitoring.Conclusion PVT should be treated with anticoagulant therapy under certain indications, but to ensure its safety and effectiveness, prospective large sample randomized controlled trials are still needed.

Citation： WANG Wenlong, LUO Zhiqiang, OUYANG Yongpeng, WANG Fei, CHEN Boxuan. Advances in anticoagulant therapy for hepatocirrhosis with portal vein thrombosis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(3): 368-373. doi: 10.7507/1007-9424.201906035 Copy

1.	Tsochatzis EA, Senzolo M, Germani G, et al. Systematic review: portal vein thrombosis in cirrhosis. Aliment Pharmacol Ther, 2010, 31(3): 366-374.
2.	Rajani R, Björnsson E, Bergquist A, et al. The epidemiology and clinical features of portal vein thrombosis: a multicentre study. Aliment Pharmacol Ther, 2010, 32(9): 1154-1162.
3.	Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med, 2011, 365(2): 147-156.
4.	Cagin YF, Atayan Y, Erdogan MA, et al. Incidence and clinical presentation of portal vein thrombosis in cirrhotic patients. Hepatobiliary Pancreat Dis Int, 2016, 15(5): 499-503.
5.	Basili S, Raparelli V, Napoleone L, et al. Platelet count does not predict bleeding in cirrhotic patients: results from the PRO-LIVER study. Am J Gastroenterol, 2018, 113(3): 368-375.
6.	Lisman T, Violi F. Cirrhosis as a risk factor for venous thrombosis. Thromb Haemost, 2017, 117(1): 3-5.
7.	Raparelli V, Basili S, Carnevale R, et al. Low-grade endotoxemia and platelet activation in cirrhosis. Hepatology, 2017, 65(2): 571-581.
8.	Violi F. Should the term coagulopathy in cirrhosis be abandoned? JAMA Intern Med, 2015, 175(5): 862-863.
9.	Violi F, Ferro D, Basili S, et al. Ongoing prothrombotic state in the portal circulation of cirrhotic patients. Thromb Haemost, 1997, 77(1): 44-47.
10.	Nocella C, Carnevale R, Bartimoccia S, et al. Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over-production. Thromb Haemost, 2017, 117(8): 1558-1570.
11.	de’Angelis N, Abdalla S, Lizzi V, et al. Incidence and predictors of portal and splenic vein thrombosis after pure laparoscopic splenectomy. Surgery, 2017, 162(6): 1219-1230.
12.	Qi X. Portal vein thrombosis: recent advance. Adv Exp Med Biol, 2017, 906: 229-239.
13.	Ogren M, Bergqvist D, Björck M, et al. High incidence of concomitant venous thromboembolism in patients with portal vein thrombosis: a population study based on 23 796 consecutive autopsies. J Thromb Haemost, 2007, 5(1): 198-200.
14.	Afifi AF, Basha OM, Maher F, et al. Portal vein thrombosis in patients with liver cirrhosis: insights to risk factors, clinical presentation and outcome. Int J Adv Res, 2015, 3(12): 1539-1548.
15.	Luca A, Caruso S, Milazzo M, et al. Natural course of extrahepatic nonmalignant partial portal vein thrombosis in patients with cirrhosis. Radiology, 2012, 265(1): 124-132.
16.	De Gaetano AM, Lafortune M, Patriquin H, et al. Cavernous transformation of the portal vein: patterns of intrahepatic and splanchnic collateral circulation detected with Doppler sonography. AJR Am J Roentgenol, 1995, 165(5): 1151-1155.
17.	Condat B, Vilgrain V, Asselah T, et al. Portal cavernoma-associated cholangiopathy: a clinical and MR cholangiography coupled with MR portography imaging study. Hepatology, 2003, 37(6): 1302-1308.
18.	Sogaard KK, Astrup LB, Vilstrup H, et al. Portal vein thrombosis; risk factors, clinical presentation and treatment. BMC Gastroenterol, 2007, 7: 34.
19.	Yerdel MA, Gunson B, Mirza D, et al. Portal vein thrombosis in adults undergoing liver transplantation: risk factors, screening, management, and outcome. Transplantation, 2000, 69(9): 1873-1881.
20.	Maruyama H, Okugawa H, Takahashi M, et al. De novo portal vein thrombosis in virus-related cirrhosis: predictive factors and long-term outcomes. Am J Gastroenterol, 2013, 108(4): 568-574.
21.	Monroe DM, Hoffman M. The coagulation cascade in cirrhosis. Clin Liver Dis, 2009, 13(1): 1-9.
22.	倪晓凌, 顾大镛, 胡国华. 前列地尔预防脾切除和断流术后门静脉系统血栓形成的历史对照研究. 中华肝胆外科杂志, 2014, 20(5): 351-354.
23.	张振, 张海涛, 张其坤, 等. 右旋糖酐联合低分子肝素钙预防门静脉高压症脾切除术后PVT及对P-sel、MMP-9、D-D三者的影响. 胃肠病学和肝病学杂志, 2019, 28(6): 668-672.
24.	Amitrano L, Guardascione MA, Menchise A, et al. Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol, 2010, 44(6): 448-451.
25.	Senzolo M, M Sartori T, Rossetto V, et al. Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis. Liver Int, 2012, 32(6): 919-927.
26.	Reiberger T, Püspök A, Schoder M, et al. Austrian consensus guidelines on the management and treatment of portal hypertension (Billroth Ⅲ). Wien Klin Wochenschr, 2017, 129(Suppl 3): 135-158.
27.	de Franchis R, Baveno Ⅵ Faculty. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol, 2015, 63(3): 743-752.
28.	European Association for the Study of the Liver. EASL Clinical Practice Guidelines: vascular diseases of the liver. J Hepatol, 2016, 64(1): 179-202.
29.	European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol, 2018, 69(2): 406-460.
30.	DeLeve LD, Valla DC, Garcia-Tsao G, et al. Vascular disorders of the liver. Hepatology, 2009, 49(5): 1729-1764.
31.	Delgado MG, Seijo S, Yepes I, et al. Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol, 2012, 10(7): 776-783.
32.	Senzolo M, Rodriguez-Castro KI, Rossetto V, et al. Increased anticoagulant response to low-molecular-weight heparin in plasma from patients with advanced cirrhosis. J Thromb Haemost, 2012, 10(9): 1823-1829.
33.	Basili S, Raparelli V, Violi F. The coagulopathy of chronic liver disease: is there a causal relationship with bleeding? Yes. Eur J Intern Med, 2010, 21(2): 62-64.
34.	Loffredo L, Pastori D, Farcomeni A, et al. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: a systematic review and meta-analysis. Gastroenterology, 2017, 153(2): 480-487.
35.	Hugenholtz GC, Northup PG, Porte RJ, et al. Is there a rationale for treatment of chronic liver disease with antithrombotic therapy? Blood Rev, 2015, 29(2): 127-136.
36.	陆申新, 陈世耀. 抗凝治疗肝硬化患者并发门静脉血栓的循证医学证据. 实用肝脏病杂志, 2016, 19(5): 624-628.
37.	Intagliata NM, Henry ZH, Maitland H, et al. Direct oral anticoagulants in cirrhosis patients pose similar risks of bleeding when compared to traditional anticoagulation. Dig Dis Sci, 2016, 61(6): 1721-1727.
38.	Borensztajn K, Stiekema J, Nijmeijer S, et al. Factor Ⅹa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation. Am J Pathol, 2008, 172(2): 309-320.
39.	Kopec AK, Joshi N, Towery KL, et al. Thrombin inhibition with dabigatran protects against high-fat diet-induced fatty liver disease in mice. J Pharmacol Exp Ther, 2014, 351(2): 288-297.
40.	Villa E, Cammà C, Marietta M, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology, 2012, 143(5): 1253-1260.
41.	Lai W, Lu SC, Li GY, et al. Anticoagulation therapy prevents portal-splenic vein thrombosis after splenectomy with gastroesophageal devascularization. World J Gastroenterol, 2012, 18(26): 3443-3450.
42.	Lee S, Kim DJ, Kim IG, et al. Use of pericholedochal plexus for portal flow reconstruction in diffuse portal vein thrombosis: case report. Transplant Proc, 2014, 46(3): 977-979.
43.	Galloula A, Rossi A, Gautier V, et al. Portal vein thrombosis associated with an acute cytomegalovirus infection. J Mal Vasc, 2014, 39(3): 224-230.
44.	Hollingshead M, Burke CT, Mauro MA, et al. Transcatheter thrombolytic therapy for acute mesenteric and portal vein thrombosis. J Vasc Interv Radiol, 2005, 16(5): 651-661.
45.	Turon F, Hernández-Gea V, García-Pagán JC. Portal vein thrombosis: yes or no on anticoagulation therapy. Curr Opin Organ Transplant, 2018, 23(2): 250-256.
46.	Qi X, Guo X, Yoshida EM, et al. Transient portal vein thrombosis in liver cirrhosis. BMC Med, 2018, 16(1): 83.

1. Tsochatzis EA, Senzolo M, Germani G, et al. Systematic review: portal vein thrombosis in cirrhosis. Aliment Pharmacol Ther, 2010, 31(3): 366-374.
2. Rajani R, Björnsson E, Bergquist A, et al. The epidemiology and clinical features of portal vein thrombosis: a multicentre study. Aliment Pharmacol Ther, 2010, 32(9): 1154-1162.
3. Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med, 2011, 365(2): 147-156.
4. Cagin YF, Atayan Y, Erdogan MA, et al. Incidence and clinical presentation of portal vein thrombosis in cirrhotic patients. Hepatobiliary Pancreat Dis Int, 2016, 15(5): 499-503.
5. Basili S, Raparelli V, Napoleone L, et al. Platelet count does not predict bleeding in cirrhotic patients: results from the PRO-LIVER study. Am J Gastroenterol, 2018, 113(3): 368-375.
6. Lisman T, Violi F. Cirrhosis as a risk factor for venous thrombosis. Thromb Haemost, 2017, 117(1): 3-5.
7. Raparelli V, Basili S, Carnevale R, et al. Low-grade endotoxemia and platelet activation in cirrhosis. Hepatology, 2017, 65(2): 571-581.
8. Violi F. Should the term coagulopathy in cirrhosis be abandoned? JAMA Intern Med, 2015, 175(5): 862-863.
9. Violi F, Ferro D, Basili S, et al. Ongoing prothrombotic state in the portal circulation of cirrhotic patients. Thromb Haemost, 1997, 77(1): 44-47.
10. Nocella C, Carnevale R, Bartimoccia S, et al. Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over-production. Thromb Haemost, 2017, 117(8): 1558-1570.
11. de’Angelis N, Abdalla S, Lizzi V, et al. Incidence and predictors of portal and splenic vein thrombosis after pure laparoscopic splenectomy. Surgery, 2017, 162(6): 1219-1230.
12. Qi X. Portal vein thrombosis: recent advance. Adv Exp Med Biol, 2017, 906: 229-239.
13. Ogren M, Bergqvist D, Björck M, et al. High incidence of concomitant venous thromboembolism in patients with portal vein thrombosis: a population study based on 23 796 consecutive autopsies. J Thromb Haemost, 2007, 5(1): 198-200.
14. Afifi AF, Basha OM, Maher F, et al. Portal vein thrombosis in patients with liver cirrhosis: insights to risk factors, clinical presentation and outcome. Int J Adv Res, 2015, 3(12): 1539-1548.
15. Luca A, Caruso S, Milazzo M, et al. Natural course of extrahepatic nonmalignant partial portal vein thrombosis in patients with cirrhosis. Radiology, 2012, 265(1): 124-132.
16. De Gaetano AM, Lafortune M, Patriquin H, et al. Cavernous transformation of the portal vein: patterns of intrahepatic and splanchnic collateral circulation detected with Doppler sonography. AJR Am J Roentgenol, 1995, 165(5): 1151-1155.
17. Condat B, Vilgrain V, Asselah T, et al. Portal cavernoma-associated cholangiopathy: a clinical and MR cholangiography coupled with MR portography imaging study. Hepatology, 2003, 37(6): 1302-1308.
18. Sogaard KK, Astrup LB, Vilstrup H, et al. Portal vein thrombosis; risk factors, clinical presentation and treatment. BMC Gastroenterol, 2007, 7: 34.
19. Yerdel MA, Gunson B, Mirza D, et al. Portal vein thrombosis in adults undergoing liver transplantation: risk factors, screening, management, and outcome. Transplantation, 2000, 69(9): 1873-1881.
20. Maruyama H, Okugawa H, Takahashi M, et al. De novo portal vein thrombosis in virus-related cirrhosis: predictive factors and long-term outcomes. Am J Gastroenterol, 2013, 108(4): 568-574.
21. Monroe DM, Hoffman M. The coagulation cascade in cirrhosis. Clin Liver Dis, 2009, 13(1): 1-9.
22. 倪晓凌, 顾大镛, 胡国华. 前列地尔预防脾切除和断流术后门静脉系统血栓形成的历史对照研究. 中华肝胆外科杂志, 2014, 20(5): 351-354.
23. 张振, 张海涛, 张其坤, 等. 右旋糖酐联合低分子肝素钙预防门静脉高压症脾切除术后PVT及对P-sel、MMP-9、D-D三者的影响. 胃肠病学和肝病学杂志, 2019, 28(6): 668-672.
24. Amitrano L, Guardascione MA, Menchise A, et al. Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol, 2010, 44(6): 448-451.
25. Senzolo M, M Sartori T, Rossetto V, et al. Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis. Liver Int, 2012, 32(6): 919-927.
26. Reiberger T, Püspök A, Schoder M, et al. Austrian consensus guidelines on the management and treatment of portal hypertension (Billroth Ⅲ). Wien Klin Wochenschr, 2017, 129(Suppl 3): 135-158.
27. de Franchis R, Baveno Ⅵ Faculty. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol, 2015, 63(3): 743-752.
28. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: vascular diseases of the liver. J Hepatol, 2016, 64(1): 179-202.
29. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol, 2018, 69(2): 406-460.
30. DeLeve LD, Valla DC, Garcia-Tsao G, et al. Vascular disorders of the liver. Hepatology, 2009, 49(5): 1729-1764.
31. Delgado MG, Seijo S, Yepes I, et al. Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol, 2012, 10(7): 776-783.
32. Senzolo M, Rodriguez-Castro KI, Rossetto V, et al. Increased anticoagulant response to low-molecular-weight heparin in plasma from patients with advanced cirrhosis. J Thromb Haemost, 2012, 10(9): 1823-1829.
33. Basili S, Raparelli V, Violi F. The coagulopathy of chronic liver disease: is there a causal relationship with bleeding? Yes. Eur J Intern Med, 2010, 21(2): 62-64.
34. Loffredo L, Pastori D, Farcomeni A, et al. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: a systematic review and meta-analysis. Gastroenterology, 2017, 153(2): 480-487.
35. Hugenholtz GC, Northup PG, Porte RJ, et al. Is there a rationale for treatment of chronic liver disease with antithrombotic therapy? Blood Rev, 2015, 29(2): 127-136.
36. 陆申新, 陈世耀. 抗凝治疗肝硬化患者并发门静脉血栓的循证医学证据. 实用肝脏病杂志, 2016, 19(5): 624-628.
37. Intagliata NM, Henry ZH, Maitland H, et al. Direct oral anticoagulants in cirrhosis patients pose similar risks of bleeding when compared to traditional anticoagulation. Dig Dis Sci, 2016, 61(6): 1721-1727.
38. Borensztajn K, Stiekema J, Nijmeijer S, et al. Factor Ⅹa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation. Am J Pathol, 2008, 172(2): 309-320.
39. Kopec AK, Joshi N, Towery KL, et al. Thrombin inhibition with dabigatran protects against high-fat diet-induced fatty liver disease in mice. J Pharmacol Exp Ther, 2014, 351(2): 288-297.
40. Villa E, Cammà C, Marietta M, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology, 2012, 143(5): 1253-1260.
41. Lai W, Lu SC, Li GY, et al. Anticoagulation therapy prevents portal-splenic vein thrombosis after splenectomy with gastroesophageal devascularization. World J Gastroenterol, 2012, 18(26): 3443-3450.
42. Lee S, Kim DJ, Kim IG, et al. Use of pericholedochal plexus for portal flow reconstruction in diffuse portal vein thrombosis: case report. Transplant Proc, 2014, 46(3): 977-979.
43. Galloula A, Rossi A, Gautier V, et al. Portal vein thrombosis associated with an acute cytomegalovirus infection. J Mal Vasc, 2014, 39(3): 224-230.
44. Hollingshead M, Burke CT, Mauro MA, et al. Transcatheter thrombolytic therapy for acute mesenteric and portal vein thrombosis. J Vasc Interv Radiol, 2005, 16(5): 651-661.
45. Turon F, Hernández-Gea V, García-Pagán JC. Portal vein thrombosis: yes or no on anticoagulation therapy. Curr Opin Organ Transplant, 2018, 23(2): 250-256.
46. Qi X, Guo X, Yoshida EM, et al. Transient portal vein thrombosis in liver cirrhosis. BMC Med, 2018, 16(1): 83.

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Advances in anticoagulant therapy for hepatocirrhosis with portal vein thrombosis

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