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![Page 1: PVT In Patients With Chronic Liver Disease Dominique-Charles Valla Hôpital Beaujon, APHP, Université Paris-7, Inserm CR3B Cooperation Bilharz-Beaujon Cairo.](https://reader035.fdocuments.net/reader035/viewer/2022062407/56649da95503460f94a95e94/html5/thumbnails/1.jpg)
PVT In Patients With Chronic Liver Disease
Dominique-Charles VallaHôpital Beaujon, APHP, Université Paris-7, Inserm CR3B
Cooperation Bilharz-BeaujonCairo - March 16-18, 2008
![Page 2: PVT In Patients With Chronic Liver Disease Dominique-Charles Valla Hôpital Beaujon, APHP, Université Paris-7, Inserm CR3B Cooperation Bilharz-Beaujon Cairo.](https://reader035.fdocuments.net/reader035/viewer/2022062407/56649da95503460f94a95e94/html5/thumbnails/2.jpg)
PVT in Patients with Cirrhosis
Epidemiology
Manifestations
Causal factors
Therapy
![Page 3: PVT In Patients With Chronic Liver Disease Dominique-Charles Valla Hôpital Beaujon, APHP, Université Paris-7, Inserm CR3B Cooperation Bilharz-Beaujon Cairo.](https://reader035.fdocuments.net/reader035/viewer/2022062407/56649da95503460f94a95e94/html5/thumbnails/3.jpg)
Prevalence of Overt PVT in Cirrhosis
Screening for HCC 0.6 %
In-Hospital 7.0 %
Necropsy 8.0 %
Before LTx or PSS 15.0 %
Okuda et al. Gastroenterology 1985;89:279-86. Chang et al. J Pathol Bacteriol 1965;89:473-80.
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Incidence of PVT in Patients with Cirrhosis
Amitrano, Endoscopy 2002. Francoz et al. Gut 2005
18% pt/yrListed for liver transplantation
Sclerotherapy 12% pt/yr
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Prevalence of Occult PVT in CirrhosisLiver explants
Wanless et al. Hepatology 1995;21:1238-47.
Small mural thrombus 64 %
Large veins (intimal fibrosis) 25 %
Small veins (intimal fibrosis) 36 %
% Veins involved
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Prevalence of Overt PVT in Schistosomiasis
Preoperative 5 %
Splenectomy/Devascularization 19 %
Distal splenorenal shunt 50 %
Widman. Hepatogastroenterology 2003
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PVT in Patients with Cirrhosis
Epidemiology
Manifestations
Causal factors
Therapy
![Page 8: PVT In Patients With Chronic Liver Disease Dominique-Charles Valla Hôpital Beaujon, APHP, Université Paris-7, Inserm CR3B Cooperation Bilharz-Beaujon Cairo.](https://reader035.fdocuments.net/reader035/viewer/2022062407/56649da95503460f94a95e94/html5/thumbnails/8.jpg)
PVT and Cirrhosis: Associations
• Portal hypertensive bleeding• Failure to control bleeding• Ascites• Hepatic encephalopathy• Hyperdynamic circulation• Intestinal ischemia or infarction
Nonami Hepatology 1992. Orloff J Gastrointest Surg 1997. D’Amico Hepatology 2003. Amitrano J Hepatol 2004.
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PVT and Cirrhosis:Associations
Nonami et al. Hepatology 1992;16:1195-8
At LTx N Liver weight
• PVT 63 17 g/Kg
• No PVT 401 21 g/KgP < .02
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Thrombosis
Advanced Liver Disease
Decreased Portal Blood Inflow
Blood stasisWall changes (PHT)
Thrombosis
Advanced Liver Disease
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PVT in Patients with Cirrhosis
Epidemiology
Manifestations
Causal factors
Therapy
![Page 12: PVT In Patients With Chronic Liver Disease Dominique-Charles Valla Hôpital Beaujon, APHP, Université Paris-7, Inserm CR3B Cooperation Bilharz-Beaujon Cairo.](https://reader035.fdocuments.net/reader035/viewer/2022062407/56649da95503460f94a95e94/html5/thumbnails/12.jpg)
THROMBOSISExternal Factors
Environmental
Local factors
Internal Factors Prothrombotic Disorders
Causes For Venous Thrombosis
Acquired
Inherited
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Inherited Prothrombotic Disorders
Loss of function
Inhibitors (PC, PS, AT)
Uncommon (< 0.1%)
High risk
Dg: Plasma level
Gain of function
Factors (FV, FII)
Common (> 2.0%)
Moderate risk
Dg: DNA analysis
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Acquired Prothrombotic Disorders
CommonModerate risk
Inflammatory statesMalignancyHyperhomocysteinemia…
UncommonHigh risk
Myeloproliferative dis.APL syndromePNHBehcet’s disease…
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Inherited Prothrombotic Disorders
Loss of function
Inhibitors (PC, PS, AT)
Uncommon (< 0.1%)
High risk
Dg: Plasma level
Gain of function
Factors (FV, FII)
Common (> 2.0%)
Moderate risk
Dg: DNA analysis
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Coagulation Inhibitors in Cirrhosis
Romero-Gomez. J Clin Gastroenterol 2000
100%
Protein C Protein S Antithrombin
A B C
50%
0%
75%
Child-Pugh
B C A B C A B CA
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Acquired Prothrombotic Disorders
CommonModerate risk
Inflammatory statesMalignancyHyperhomocysteinemia…
UncommonHigh risk
Myeloproliferative dis.APL syndromePNHBehcet’s disease…
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PVT and Cirrhosis: Antiphospholipid Ab
Mangia, Am J Gastroenterol 1999. Dalekos, Eur J Gastro Hepato 2000.Munoz-Rodriguez, J Hepatol 1999. Prieto, Hepatology 1996.
Quintarelli, J Hepatol 1994. Violi, Hepatology 1997. Romero-Gomez J Clin gastro 2000
• ACL common in chronic liver diseases (20%)
• Usually non specific (low fluctuating titer, no LA)
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Risk Factors for Portal Vein Thrombosis.Cirrhosis without HCC
Univariate: Age, Child-Pugh class, Surgery for portal hypertensionEndoscopic sclerotherapyProthrombotic features
Mangia, Am J Gastroenterol 1999. Nonami, Hepatology 1992. Davidson, Transplantation 1994. *Amitrano, J Hepatol 2004.
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PVT and Cirrhosis: Prothrombotic Disorders
With PVT No PVT p
Amitrano et al. Hepatology 2000;31:345-8.
F. V LeidenF. II gene mutationC677T MTHFRAt least oneTwo or more
13 %35 %43 %70 %22 %
NS< .05< .05< .01
7 %2 %5 %
14 %0
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Risk Factors for Portal Vein Thrombosis.Cirrhosis without HCC
Univariate: Age, Child-Pugh class, Surgery for portal hypertensionEndoscopic sclerotherapyProthrombotic features
Mangia, Am J Gastroenterol 1999. Nonami, Hepatology 1992. Davidson, Transplantation 1994. *Amitrano, J Hepatol 2004.
Multivariate: G20210A FII (OR 5.94*)
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PVT in Patients with Cirrhosis
Epidemiology
Manifestations
Causal factors
Therapy
![Page 23: PVT In Patients With Chronic Liver Disease Dominique-Charles Valla Hôpital Beaujon, APHP, Université Paris-7, Inserm CR3B Cooperation Bilharz-Beaujon Cairo.](https://reader035.fdocuments.net/reader035/viewer/2022062407/56649da95503460f94a95e94/html5/thumbnails/23.jpg)
PVT and Cirrhosis: Why to treat?
• To prevent aggravation ?
• To facilitate transplantation
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Portal Vein Thrombosis Clinical results of anticoagulant therapy
• In patients without cirrhosis
• In patients with cirrhosis
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Acute PVT: Complete Recanalization
Pts at risk: 91 50 33 19 15 7 4
0 3 6 9 12 15 18
Time to recanalization (months)
0
20
40
60
Rec
anal
izat
ion
(%)
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Chronic Portal Vein Thrombosis
Condat et al. Gastroenterology 2001; 120:490
Thrombosis
6.0
yesno yesnoAnticoagulation Anticoagulation
1.2
Bleeding
7
17
per
100
pat
ien
tsp
er y
ear
p = 0.015
p = 0.212
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Orr et al. Hepatology 2005; 42: 212A (AASLD San Francisco 2005)
Chronic portomesenteric venous thrombosis
HR for Death
yesno
Warfarine
0.10
1.00p=0.038
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Patients on the Waiting List for LTx
PVT before transplantation(n = 29)
Anticoagulation(n = 19)
Recanalization(n = 8)
Francoz, Gut 2005
No anticoagulation(n = 10)
Recanalization(n = 0)
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TIPS for PVT in Cirrhosis
• Limited data• Feasible and safe• Risk of obstruction unclear • Risk of encephalopathy unclear• Benefit unclear
Senzolo Alim Pharmacol Therap 2006. Van Ha Cardiovasc Intervent Radiol 2006. Bauer Liver Transplant 2006
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PVT and Cirrhosis: Summary
• Common in end-stage cirrhosis
• Uncommon in well-compensated cirrhosis
• Causal factors: surgery, stasis, thrombophilias
• A marker for severity: certainly
• A cause for aggravation: uncertain
• A limitation for liver transplantation: certainly
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PVT and Cirrhosis: What we do in Beaujon
Objectives: Recanalization (recent thrombus)Prevention of thrombus extension
Indications: → Child A with thrombophilia→ Patients listed for LTx
Monitoring: Anti-Xa 0.5 U/ml Factor II 25% to 35%
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Hemostasis in Cirrhosis
• Normal thrombin generation in platelet-poor plasma.
• Decreased thrombin generation in severely thrombocytopenic blood.
• Elevated levels of vWF support platelet adhesion despite reduced functional capacities.
Caldwell. Hepatology 2006
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INR in Patients with Cirrhosis
• Not related to prothrombin levels along the same regression line as for Vitamin K antagonists.
• Due to uncarboxylated metabolites of coagulation factors
• Interlaboratory variability.
→ Adjustment based on Factor II level 25-35%?
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Patients on the Waiting List for LTx
PVT before transplantation24
Complete3
Recanalization0
Francoz, ILTS 2008
Partial21
Recanalization*15
* No post-OLT PVT
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Recanalisation
83 %
Anticoagulation (alone, n = 27)
Condat. Hepatology 2000
Thrombolysis (in situ, n = 20)
75 %
Acute Portal Vein Thrombosis
Holliingshead. J Vasc Interv Radiol 2005
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Acute Portal Vein Thrombosis
0
100Major Bleeding
60%
Thrombolysis (in situ, n = 20)
5%
Anticoagulation (alone, n = 27)
Condat. Hepatology 2000
Holliingshead. J Vasc Interv Radiol 2005
%