3 e Giornate Gastro-Epatologiche Cuneesi
Complicanze della Cirrosi
Casa Regina Montis Regalis - Vicoforte 19 febbraio 2010
Trombosi portale nei cirrotici e non: quale approccio
Wilma Debernardi Venon
Az. Osp. San Giovanni Battista di Torino
Portal Vein Thrombosis
portal vein
mesenteric vein
splenic vein
EHPVO thrombosis
invasion
constriction
rare: general population 4.4%-15%: cirrhosis 0.6%-30%: OLT
6.5%-40%: HCC
J Hepatology 2004 Alim Pharm Therapy 2009portal and
mesenteric veins portal vein
mesenteric vein
portal,
mesenteric and splenic veins portal and
splenic veins
Portal Vein Thrombosis
37%
34%
17%
4% 8%
Portal vein thrombosis: 61% asymptomatic
Mesenteric vein thrombosis: 92% symptomatic, 45% intestinal infarction
Portal Vein Thrombosis
Portal vein obstruction
Apoptosis hepatic cells Mitotic activity
Arterial vasodilation Collateral veins
Total hepatic blood flow Portal pressure increase
Esophageal varices
Hypertensive gastropathy Hyperkinetic circulation
Portal Vein Thrombosis
States of thrombophilia Local factors favoring PVT
W J Gastroenterol 2010
Predictive factors:
• male sex
• previous surgery
• variceal endoscopic treatment
• previous variceal bleeding
• low platelets count
• advanced liver failure
• portal flow velocity < 15 cm/sec
J Hepatology 2009
Risk factor PVT patients (%)
Myeloproliferative disorders 30-40
Atypical 14
Classical 17
Antithrombin deficiency 0-26
Protein C deficiency 0-26
Protein S deficiency 2-30
Factor V Leiden mutation 6-32
Prothrombine mutation 14-40
TT677 MTHFR genotype 11-50
Antiphospholipid syndrome 6-19
Hyperomocisteinemia 12-22
Recent pregnancy 6-40
Recent oral contraceptive use 12
Adult patients with non malignant and non cirrhotic , acute or chronic PVT
W J Gastroenterol 2010
Characteristics associated with the JAK2V617F mutation in 137 patients with portal vein thrombosis
PVT patients Without JAK2V617F (90 pts) With JAK2 V617F (47 pts) P
Age, y 49 [37-62] 53 [36-60] .96
Males, % 52 (57.8%) 25 (53.2%) .72
Hemoglobin, g/dL 13 [10.8-14.5] 12.9 [12.1-14.5] .73
Hematocrit, % 38.2 [33-43] 40 [37-45] .06
MCV, fL 87.1 [82.2-91] 86.2 [82.2-90] .64
WBC count, x109/L 5.35 [3.9-7.1] 6.8 [4.9-9.6] .005
ANC, x109/L 3.48 [2.5-4.6] 4.76 [3.4-6.5] .016
Platelet count, x109/L 141 [101-230] 323 [214-437] <.001
Spleen size BCM, cm 0 [0-3] 8 [4-15] <.001
Serum EPO, mU/mL 14 [8.2-27] 10.5 [6.8-14.7] .027
Measured RCM, mL/kg 26.9 [24-31.7] 34.5 [30-38] <.001
Predicted RCM, mL/kg 25 [23.2-26] 26.4 [24-27.5] .075
RCM more than 125% of predicted 11/41 (26.8%) 20/32 (62.5%) .004
AST, ULN 28 [19.5-40] 30 [22.5-42.5] .41
ALT, ULN 35 [20-52.5] 34 [25-62.5] .68
Serum bilirubin, µmol/L 15.4 [12.5-25.8] 16 [13-25] .71
Serum creatinine, µmol/L 74 [61.9-88] 75 [66.5-79.8] .84
Serum albumin, g/dL 38.5 [35.2-42.7] 40 [38-45] .054
Factor V, % 92 [63.2-109.5] 63.5 [47.7-86] .004
Blood 2008
Risk factors of portal vein thrombosis in liver cirrhosis
J Hepatology 2004
Combination of acquired plus genetic factors in cirrhotic patients with or without of portal vein thrombosis
Eur J Gastroenterol Hepatol 2005
Clinical and Radiological Characteristics at Diagnosis in 102 Patients with Acute PVT
Sex, female/male 50/52
Age, median (range) 48 (16-84)
Abdominal pain, n (%) 93 (91)
Fever, n (%) 54 (53)
Ascites, n (%) 39 (38)
Small volume ascites, n (%) 34 (33)
Clinical ascites, n (%) 5 (5)
Splenomegaly at imaging, n (%) 38 (37)
Hepatomegaly at imaging, n (%) 25 (25)
Prothrombin ratio, %, median (range) 84 (27-114)
Serum bilirubin, mol/L, median (range) 15 (2-207)
Alanine aminotransferase, median (range) 46 (13-1,484)
Serum creatinine, mol/L, median (range) 76 (28-163)
Hemoglobin, mmol/L, median (range) 8 (3-12.5)
Leukocytes, 109/L, median (range) 9.3 (1-34)
Platelets, 109/L, median (range) 274 (55-949)
C-reactive protein, UI, median (range) 52 (1-529)
Elevated C-reactive protein or fever, n (%) 86 (84)
Hepatology 2010
Patients with cancer or cirrhosis N = 19 Patients without cancer and cirrhosis N = 48
Acute Chronic N (% of total) Acute Chronic N (% of total
Abdominalia 7 (70%) 5 (56%) 46 (63%) 16 (94%) 18 (58%) 34 (71%) Splenomegaly 7 (70%) 5 (56%) 12 (63%) 10 (59%) 26 (84%) 36 (75%)
Fever 5 (50%) 2 (22%) 7 (37%) 10 (59%) 5 (16%) 15 (31%)
Haemorrhage 6 (22%) 5 (35%) 11 (58%) 0 9 (29%) 9 (19%)
Ascites 4 (40%) 2 (22%) 6 (32%) 8 (47%) 10 (38%) 18 (38%)
Weight loss 1 (10%) 2 (22%) 3 (16%) 9 (53%) 7 (23%) 16 (33%)
Total 10 (53%) 9 (47%) 19 (100%) 17 (35%) 31 (65%) 48 (100%)
Acute Chronic N (% of total) Acute Chronic N (% of total) Portal HG 4 (40%) 3 (33%) 7 (37%) 5 (29%) 16 (52%) 21 (44%) Gastric varices 4 (40%) 4 (44%) 8 (42%) 4 (24%) 16 (52%) 20 (42%) OV, small 4 (40%) 6 (67%) 10 (53%) 7 (41%) 18 (58%) 25 (52%) OV, large 1 (10%) 1 (11%) 2 (11%) 1 (6%) 10 (32%) 1 (23%) Haemorrhages (1–2) 2 (20%) 4 (44%) 6 (32%) 0 10 (32%) 10 (21%) Ascites 4 (40%) 4 (44%) 8 (42%) 8 (47%) 12 (39%) 20 (42%) Total 10 (53%) 9 (47%) 19 (100%) 17 (35%) 31 (65%) 51 (100%)
BMC Gastroenterol 2007
Outcome of portal vein thrombosis
overall mortality: < 10% malignancy or cirrhosis: 26%
bowel ischemia:20-50% variceal bleeding:< 6%
Gut 2001
Treatment of portal vein thrombosis
portal vein recanalization prevention of thrombosis extension
anticoagulation
• EBPM 100 U/Kg per 2/die
• dicumarolici
Acute PVT
• < first week
• 6 months and long term if thrombophilia or MVT
• antibiotic therapy
PV complete recanalization: 50-80%
mesenteric vein: 60% splenic vein: 54%
Cavernoma evolution: > 40%
cirrhosis non cirrhosis
Hepatology 2010 J of Hepatology 2000
bleeding: 9%
variceal bleeding: <3%
Nat Clin Prac Gastr Hepat 2005 Hepatology 2010
Treatment of portal vein thrombosis
Chronic PVT
cirrhosis non cirrhosis
portal hypertension recurrent thrombosis portal colangiopathy
Anticoagulation therapy if:
• no cavernoma
•MV thrombosis
• thrombophylia
• OLT
Anticoagulation therapy if:
• no cavernoma
• thrombophylia
Prevention and treatment of gastrointestinal bleeding Variceal banding
Treatment of portal colangiopathy
• Biliary endoprothesis
• TIPS or surgical shunt
• bilioenteric anastomosis
• mesenteric--> left portal vein bypass
Nat Clin Prac Gastr Hepat 2005 Hepatology 2010
J of Hepatology 2000
Treatment of portal vein thrombosis
Thrombolysis
• limited experience
• complications
TIPSS
• cirrhosis
• > 50% PVT
• OLT
J Vasc Int Rad 2005 W J Gastr 2010
Portal Vein Thrombosis and OLT
Transplantation 2000
• Tipo 1: < 50% PVT
• Tipo 2: > 50% PVT
• Tipo 3: PVT completa + trombosi prossimale della VMS
• Tipo 4: PVT completa + trombosi completa della VMS
. Thrombectomy and low dissection is the method of choice for revascularization in grades 1 and 2 PVT
. In grade 3 PVT, a donor iliac vein graft is interposed between the donor distal SMV and the graft portal vein.
. In grade 4 PVT, a collateral of the portal system is used as an inflow vessel
0.004 1.9 ± 2.3
2.4 ± 3.1 Fabbisogno trasfusionale (U±SD)
0.0005 4.2 ± 3.9
7.4 ± 8.5 ICU degenza (g±SD)
77%
363 ± 83 7.8%
42%
2.4%
Non PVT (293 pz)
0.95 75%
Spvv a 3aa
0.0005 417 ± 103
Durata della chirurgia (min±SD)
0.98 4%
Mortalità ospedaliera
0.19 53%
Complicanze infettive
0.0005 15%
Incidenza di PVT post OLT
p PVT
(42 pz)
Clin Transplant 2007
Portal Vein Thrombosis and OLT
63.9%
63.9%
65.6%
65.6%
30%
PVT
<0.05 84.2%
Spvv pz A 1 aa
<0.05
<0.05 0.04
<0.001 p
67.9%
76.7%
76.3%
12.4%
Non PVT
Spvv graft A 5 aa Spvv graft
A 1 aa Spvv pz
A 5 aa Mortalità
perioperatoria
Liver Transplantation 2000;
0.0004 0.2
Spvv graft a 5aa
<0.0001 Spvv pz a 5aa 0.5
Non-PVT vs Grado 2-4 p
Non-PVT vs Grado 1 p
Portal Vein Thrombosis and OLT
5U 5h 9.4%
1.4%
1.1%
Non PVT
< 0.0001 10U
Fabbisogno trasfusionale
< 0.0001 6h
Durata della chirurgia
0.01 20%
Insufficienza renale necessitante dialisi post OLT
0.02 6.6%
Primary non function
0.04 5%
Incidenza di PVT post OLT
p PVT
