2. Sequence
• Portal vein thrombosis
1. In the absence of underlying liver disease
2. In patients with cirrhosis
• Portal vein thrombosis in HCC (PVTT)
a) Introduction
b) Etiology
c) Clinical Features
d) Diagnosis
e) Management
3. Introduction
• The term portal vein thrombosis (PVT) refers to the development of a thrombus in the
portal vein - can extend into any of the right and left branches of the portal vein, the
superior or inferior mesenteric vein, and the splenic vein.
“PVT may be best defined as a syndrome in which the presence of a thrombus in the
portal vein or its branches presents either as an incidental finding on abdominal imaging;
or with abdominal signs and symptoms that represent complications of portal
hypertension; or a composite of both acute abdominal and portal hypertensive
manifestations in the presence or absence of cirrhosis and/or malignancy.”
Sarin et al. Gastroenterology
2016;151:574–577
4. Pathophysiology of PVT
The pathophysiology of portal vein
thrombosis encompasses one or more
features of Virchow's triad, viz.,
reduced portal blood flow, a
hypercoagulable state or vascular
endothelial injury
6. • Noncirrhotic, nontumorous PVT is the second most frequent cause of portal
hypertension worldwide, accounting for a larger proportion of cases in developing
countries than in Western countries.
• A different background prevalence of infectious and inflammatory causes and limited
access to medical care are usually proposed to explain this difference.
Epidemiology
7. Etiology
• Comprehensive investigations can identify systemic prothrombotic factors in
approximately 60% of patients but local triggering factors in less than 40% of cases.
• A combination of two or more pro-thrombotic factors has been found in 52% of
PVT patients, which justifies comprehensive investigations, even when predisposing
or precipitating factors have already been shown.
• Still, currently available investigations fail to identify a causal factor in approximately
20% of patients.
Amitrano L, Guardascione MA, Brancaccio V, et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J Hepatol. 2004;40:736–741.
8. Etiology
No factor: 20%
Other systemic factors
Autoimmune disease, IBD, vasculitis,
sarcoidosis, connective tissue disease, behcet
disease, CMV infection.
Any abdominal organ malignancy
Cirrhosis
Abdominal trauma
Liver transplantation
30-40%
AASLD 2009
6-19%
6-32%
0-26%
2-30%
0-26%
12%
9. General Risk Factors
• Myeloproliferative Neoplasms
• Myeloproliferative neoplasms (MPNs) have been found in approximately 30% of patients
with PVT.
• In PVT patients, however, hyper-splenism and hemo-dilution may mask the increased
blood cell counts.
10. • MPN diagnosis has been facilitated by testing for the V617F mutation of the Janus
kinase 2 gene (JAK2).
• The prevalence of MPNs and JAK2 mutation among patients with non-cirrhotic
PVT has been estimated at 31.5% and 27.7%, respectively. JAK2 mutation has been
detected in 15.4% of PVT patients without typical MPN features.
• Somatic mutations of the gene encoding calreticulin (CALR) have been identified in
approximately 2% of JAK2 V617F–negative patients with PVT.
General Risk Factors
11. • Inherited thrombophilia
• Pooled prevalence
• Antithrombin – 3.9%
• Protein C – 5.6%
• Protein S deficiency – 2.6%
• Methylene tetrahydrofolate reductase gene (MTHFR) polymorphism – 11% (not
higher than expected in general population).
• Factor V Leiden mutation – 3-9%
• G20210A prothrombin gene mutation – 9-22%
General Risk Factors
12. Acquired pro-thrombotic disorders
• Antiphospholipid syndrome (venous and arterial thromboses, or recurrent fetal
losses, in the presence of antiphospholipid antibodies.)
• In patients with PVT, the reported prevalence for antiphospholipid antibodies was
approximately 5% to 10%.
13. Acquired pro-thrombotic disorders
• Other autoimmune-mediated diseases, vasculitis, sarcoidosis, and connective tissue
disease, may also be associated with PVT.
• The incidence of PVT was 6.4% in hospitalized patients with acute cytomegalovirus
infection, being higher in immune-competent than in immune-compromised patients.
Amitrano L, Guardascione MA, Brancaccio V, et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J Hepatol. 2004;40:736–741.
Alone, exposure to female hormones does not appear to cause PVT. A female
predominance among patients with PVT has not been found.
Oral contraceptive use and pregnancy have been reported to trigger PVT only when local
or other general pro-thrombotic factors were present.
14. Local factors
• Local risk factors (i.e., surgery or infectious or inflammatory conditions in the
splanchnic area) were found in 21% of patients.
• The identification of a local factor should not prevent the investigation of a systemic
pro-thrombotic factor because one third of patients with a local factor also had a
general pro-thrombotic disorder.
• Septic thrombophlebitis of the portal vein (so-called pylephlebitis) is usually
related to an infection in the region drained by the portal venous system, mostly
diverticulitis and appendicitis.
Amitrano L, Guardascione MA, Brancaccio V, et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J Hepatol. 2004;40:736–741.
15. Clinical and Laboratory Features
• Acute Portal Vein Thrombosis
• Acute portal vein thrombosis (PVT) refers to the recent formation of a thrombus
within the portal vein and/or its branches and/or its radicles.
• Abdominal pain is present in most patients. Other features include fever, high
leukocyte count, and high C-reactive protein level, all related to a systemic
inflammatory response syndrome developing in the absence of infection.
• Splenomegaly in 40 % of cases (half of them have underlying myeloproliferative
disorder).
16. • Acute Portal Vein Thrombosis
• Ischemia or infarction of the small bowel should be suspected in patients with:
• persisting intense pain despite adequate anticoagulation (beyond 5-7 days);
• hematochezia;
• guarding;
• ascites (clinical ascites in 5%); or
• Multi-organ failure with increased lactate levels or metabolic acidosis.
Clinical and Laboratory Features
17. • Pylephlebitits
• Clinical features of pylephlebitis include a high, spiking fever with chills, a painful liver,
and sometimes shock.
• Blood cultures usually grow Bacteroides species, with or without other enteric species.
• Multiple, small liver abscesses are common in this setting.
• Acute septic PVT is always associated with an abdominal focus of infection.
• This primary focus can be easily overlooked clinically and, therefore, detected only by
careful review of the CT scan or MRI.
• Sepsis-related cholestasis can be present.
Clinical and Laboratory Features
18. Clinical and Laboratory Features
• Chronic Portal Vein Thrombosis
• Following acute thrombosis, in the absence of recanalization, the portal venous
lumen obliterates, whereas tortuous collateral vessels bypassing the thrombosed
portion of the portal vein develop and together form the so-called cavernoma.
• Portal hypertension, recurrent thrombosis, and cholangiopathy are the main
complications of chronic PVT.
• Complete occlusion of the portal vein trunk, or of its two main branches is virtually
always associated with portal hypertension and the development of portosystemic
collaterals.
19. Chronic PVT (C/F)
• Portal Hypertension.
• Bleeding is the most frequent portal hypertension–related complication. Varices may
belong to the portosystemic collateral circulation (in the esophagus and the gastric
fundus) or to the portal cavernoma (in the gastric antrum and the duodenum).
• Bleeding-related mortality in patients with PVT is lower than in patients with
cirrhosis, probably because of the preserved liver function.
20. • Portal Hypertension.
• Ectopic varices, in the duodenum, anorectal region, and gallbladder wall, are more
common than in patients with cirrhosis.
• Ascites is uncommon, and is usually (but not constantly) triggered by recent
gastrointestinal bleeding or infection. Ascites purely related to hepatic dysfunction occurs
late in the course of PVT.
• Overt hepatic encephalopathy is rare in the absence of a concurrent precipitating factor.
By contrast, subclinical encephalopathy appears to be common (50%).
Chronic PVT (C/F)
21. • Recurrent Thrombosis
• Recurrent thrombosis is the next most frequent complication behind bleeding.
• It mostly affects the splanchnic area. Pro-thrombotic conditions constitute an
independent risk factor for recurrent thrombosis
• Involvement of the superior mesenteric vein is associated with a worse outcome.
Chronic PVT (C/F)
22. • Portal cavernoma cholangiopathy
• The term portal cavernoma cholangiopathy refers to abnormalities of the entire
biliary tract, including intrahepatic and extrahepatic bile ducts, the cystic duct, and the
gallbladder in patients with portal cavernoma.
• It is attributed to imprinting on the bile ducts or their lumen by collaterals composing
the cavernoma.
• Ischemic damage to the biliary tree has also been suggested to explain part of portal
cavernoma cholangiopathy.
Chronic PVT (C/F)
23. • Portal cavernoma cholangiopathy
• Clinical impact is more limited than morphologic changes. (bile duct change in 92% in
MRC)
• Elevated serum ALP levels, bilirubin levels and ALT levels were observed in 30% to
80%, 50%, and 30% of patients with portal cavernoma cholangiopathy, respectively.
• Severe and life-threatening manifestations (cholecystitis, cholangitis, obstructive jaundice)
were even less common, and occurred in 5% to 35% of the patients. (Present in Grade
III cholangiopathy (namely, strictures with dilatations).
Chronic PVT (C/F)
Turnes J, García-Pagan JC, Gonzalez M, et al. Portal hypertensionrelated complications after acute portal vein thrombosis: impact of early anticoagulation. Clin Gastroenterol Hepatol.
2008;6:1412–1417.
24. Imaging features
Acute Portal Vein Thrombosis
• The direct visualization of a hyperechogenic thrombus in the portal lumen is
inconstant. Therefore duplex ultrasonography is needed to show an absence of flow
within the portal vein.
• Contrast-enhanced computed tomography (CT) in the portal phase shows the
absence of enhancement of the lumen corresponding to the portal vein thrombus.
• A spontaneously hyperattenuating thrombus dates back to less than 30 days after the
onset of symptoms. The absence of a well-developed cavernoma is an additional
feature suggesting that PVT is recent, because a cavernoma is visible as early as 15
days after the onset of abdominal pain.
25. Sensitivity/specifity of imaging modalities
• Overall the sensitivity and specificity of ultrasound for detecting portal vein
thrombosis ranges from 80 to 100% with an accuracy of 88–98%.
• The diagnostic sensitivity and specificity for Color Doppler Ultrasound (CDUS) in
detecting portal vein thrombosis varies from 66% to 100%.
• The sensitivity and specificity of MRI for detecting main PVT are 100% and 98%.
27. Subcostal oblique parasagittal image with color flow Doppler demonstrates a lack of
color flow in the portal vein (black arrow).
28. Image A shows the thrombus as a filling defect in the contrast-filled spleno-portal junction.
Image B is a coronal reconstruction showing some sort of low-density structure in the portal
vein
29. Imaging features
• Chronic Portal Vein Thrombosis
• The diagnosis is made by the demonstration of the cavernoma on imaging by any of
duplex ultrasonography, CT scan, or magnetic resonance angiography. The original
portal vein is replaced by serpiginous collaterals in the porta hepatis which are enhanced
during the portal phase.
• Other imaging features include a combination of atrophy of left lateral liver segments
with segment IV hypertrophy. Hepatic arteries are usually enlarged.
• Enlarged spleen size is common and can be related to portal hypertension, to MPN, or
to both factors
30. Cavernoma cholangiopathy (imaging)
• Magnetic resonance cholangiography coupled with magnetic resonance angiography
is recognized as the reference procedure for diagnosing portal cavernoma
cholangiopathy.
• Changes consist mainly of stenoses, upstream dilatation, and irregularities in the
caliber of the bile ducts.
• A recent study found that bile duct changes develop within 1 year after the acute
episode, and thereafter remain stable.
31. • A, Computed tomography scan in the portal phase after intravenous injection of contrast agent shows:
• A: A hyperattenuated network of collaterals (arrow) and splenomegaly (star).
• B: Magnetic resonance angiography shows a pseudotumoral cavernoma, seen as a solid-like mass, enhanced in
the portal phase of contrast agent injection.
• C: Magnetic resonance cholangiography shows portal cavernoma cholangiopathy, seen as multiple imprinting on
the lumen of the bile ducts.
32. • MR portography has been shown to be superior to color Doppler US in detecting
partial thrombosis, and occlusion of the main portal venous vessels.
• It also identifies porto-splenic collaterals and portal venous vessels more adequately
that cannot be visualized on color Doppler.
• True fast imaging with steady state precession (true FISP) with MRI has been shown
to be a useful adjunct to contrast enhanced MR angiography in severely debilitated
patients, where respiratory motion may degrade the images or when the use of
contrast medium is not possible due to poor venous access.
Imaging features
33.
34. Partial thrombosis of main portal vein. Coronal MIP image (a) and 3D volume-
rendered image (b) from a non-contrast MR portography using T-SLIP sequence
showing eccentric mural narrowing of the main portal vein (yellow arrow) representing
partial thrombosis.
35. Outcome (Acute PVT)
• The complications of recent PVT are related to the extension of the thrombus.
• There is little effect on the intestine as long as the mesenteric venous arches remain
patent.
• Ischemia results from the extension of the thrombus into the mesenteric veins and
the mesenteric venous arches.
36. • Intestinal infarction is the most dreaded complication of MVT, and can occur when
ischemia is prolonged for 5 days to 7 days.
• Intestinal infarction has been reported in 4% to 58% of patients with acute MVT.
• Severe disability may result from either short bowel syndrome or post-ischemic
intestinal stenosis.
Outcome (Acute PVT)
Sogaard KK, Astrup LB, Vilstrup H, Gronbaek H. Portal vein thrombosis; risk factors, clinical presentation and treatment. BMC Gastroenterol. 2007;7:34.
37. Outcome (Acute PVT)
• Mortality in the past was 20%–50% with acute PVT and other splanchnic vessels, but
with an early diagnosis, increased clinical awareness, improved diagnostic techniques
and use of early anticoagulation the 5 yr survival rate has improved to 85%.
• However in the event of bowel infarction and multi organ failure, the in hospital
mortality is approximately 20–50%.
Condat B, Pessione F, Hillaire S, et al. Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy. Gastroenterology. 2001;120:490–497.
38. Outcome (Chronic PVT)
• The overall mortality in chronic onset PVT is less than 10%.
• The outcome of patients with a cavernoma is relatively good, being determined
mostly by patient age, portal hypertension, associated thrombosis of the superior
mesenteric vein, and the underlying condition causing thrombosis.
• Recurrent bleeding from portal hypertension is the most common complication,
followed by recurrent thrombosis at splanchnic or extrasplanchnic sites.
Condat B, Pessione F, Hillaire S, et al. Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy. Gastroenterology. 2001;120:490–497.
39. D/D for variants of PVT
Variant of
PVT
Differentials Differentiating features
Acute PVT Acute abdominal conditions like pancreatitis,
cholecystitis, appendicitis, cholangitis, liver
abscess, abd. Surgery or trauma, SBP
US/CT/MRI will detect fresh thrombus or any
local intra-abdominal inflammatory focus or
both together
Chronic PVT NCPF (Non-cirrhotic portal fibrosis)
Cirrhosis
Imaging shows preserved portal vein in NCPF
and cavernoma formation in EHPV/chronic
PVT
Ascites, jaundice, hepatic encephalopathy are
common in cirrhosis and uncommon in C-PVT.
Liver functions are preserved in C-PVT.
Imaging shows irregular liver outline and dilated
portal vein in cirrhosis.
41. Anticoagulation - Acute PVT
• The aim of therapy for acute PVT is to prevent mesenteric venous infarction and to
achieve portal vein recanalization.
• Increased use of early anticoagulation in patients with acute PVT/MVT has been associated
with an incidence of intestinal infarction decreasing from 33% in patients who did not
receive anticoagulation to 2%.
• In a recent prospective study of 95 patients with acute PVT receiving anticoagulation
therapy, thrombus extension was prevented in all patients who had early initiation of
anticoagulation therapy.
Plessier A, et al: Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study. Hepatoloy 51:210–218, 2010.
42. • Recanalization of the thrombosed veins is obtained in 30% to 80% of anticoagulated
patients, depending on the site of occlusion.
• Recanalization of the portal vein has been shown to occur within the first 6 months of
anticoagulation, or not to happen.
• Ascites, an occluded splenic vein, and underlying pro-thrombotic disorders have been
associated with a failure to recanalize the portal vein.
• In the presence of fever or leukocytosis, antibiotics have been used and reports of
recanalization of pylephlebitis with antibiotic therapy alone.
Anticoagulation - Acute PVT
Plessier A, et al: Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study. Hepatoloy 51:210–218, 2010.
43. Anticoagulation (chronic PVT)
• Reasonable objectives for long-term anticoagulation consist of preventing recurrent or
extensive thrombosis, thereby protecting the patient from intestinal infarction and from
portal hypertension– related complications.
• In patients without a pro-thrombotic condition, the use of anticoagulation therapy should
be decided on an individual basis, taking into account the potential benefits of
anticoagulation and the risk of bleeding related or unrelated to portal hypertension.
• In patients with intestinal infarction, long-term anticoagulation has been recommended on
the basis of a decreased risk of recurrent thrombosis in patients who receive
anticoagulation therapy.
44. • Bleeding occurs in approximately 10% of patients.
• Independent predictors of gastrointestinal bleeding were a previous episode and the size of
esophageal varices.
• Accordingly, anticoagulation therapy should be started after adequate prophylaxis of variceal
bleeding has been initiated.
• In most studies, anticoagulation therapy was based on unfractionated heparin or low
molecular weight heparin in high doses within the first few weeks, and this was then replaced
by vitamin K antagonists, targeting an international normalized ratio between 2 and 3.
Anticoagulation (chronic PVT)
Turnes J, García-Pagan JC, Gonzalez M, et al. Portal hypertensionrelated complications after acute portal vein thrombosis: impact of early anticoagulation. Clin Gastroenterol Hepatol.
2008;6:1412–1417.
45. Traditional vs DOACs
• For many decades, standard care was to start with unfractionated heparin or low
molecular weight heparin (LMWH), then bridging to oral vitamin K antagonist
(VKA) for long-term anticoagulation.
• Unfractionated heparin has been largely replaced by LMWH in most clinical
situations due to the ease of outpatient administration, given subcutaneously once or
twice a day, without the need for laboratory monitoring.
• The recommended dose for enoxaparin is 1 mg/kg every 12 hours (maximum dose
150 mg) and for dalteparin is 10,000 to 18,000 IU once a day (depending on weight).
• In treatment and prevention of VTE and PE, the daily oral VKA dose targets to
individualized therapeutic international normalized ratio value of 2.5 (range 2-3).
46. • DOACs have been in increasing use for treatment of VTE, in a variety of clinical
settings.
• This group of agents includes orally available direct factor Xa inhibitors (rivoraxaban,
apixaban, edoxaban, betrixaban) and the direct thrombin inhibitor dabigatran.
• DOACs avert daily subcutaneous injections of LWMHs and the frequent monitoring
of VKA.
• In patients with heparin-induced thrombocytopenia, DOACs represent effective
options for anticoagulation.
Traditional vs DOACs
48. Proposed algorithm for the management of anticoagulation therapy in patients with portal vein
thrombosis in the absence of underlying liver disease.
ZAKIM
51. Management of Portal Hypertension–Related
Complications
• Patients with acute PVT should be screened for gastroesophageal varices within 6
months after the acute episode as gastroesophageal varices may develop as early as 1
month after acute PVT.
• In patients without varices on early endoscopy and persistent occlusion of the portal
vein, varices develop mostly during the first year of follow-up.
• Thus in the absence of varices at 6 months, endoscopy should be repeated at 12
months. In accordance with the guidelines for cirrhosis to PVT, further follow-up
screening endoscopies should be performed every 2 years.
52. • In patients with chronic PVT, nonselective β-adrenergic blocking agents have been
reported in retrospective cohort studies to decrease the risk of bleeding in patients
with large varices and to improve survival.
• The acute variceal bleeding episode could be managed by application of the
guidelines for cirrhosis.
• Endoscopic band ligation is safe and effective for the treatment of variceal bleeding.
Management of Portal Hypertension–Related
Complications
53. Radiologic Interventions
• Local thrombolytic therapy and catheter-directed thrombectomy have been proposed
for patients with extensive thrombosis in whom intestinal infarction is expected.
• The superior mesenteric arterial route has been used for pharmacologic
thrombolysis.
• Transhepatic transcapsular or transjugular routes have been used for pharmacologic
thrombolysis and thrombectomy.
Hollingshead M, et al: Transcatheter thrombolytic therapy for acute mesenteric and portal vein thrombosis. J Vasc Interv Radiol 16:651–661, 2005.
54. • Catheterization of SMA operatively and intra-arterial infusion of thrombolytic drugs
like recombinant tissue plasminogen activator, urokinase and streptokinase have all
been shown to have gratifying results.
• A recanalization of the superior mesenteric vein was reported in 75% of patients as
compared with 60% of patients using prolonged anticoagulation therapy alone in a
recent prospective observational study.
• Major procedure-related bleeding occurred in 60% of patients, with occasional cases
of fatal outcome.
Radiologic Interventions
Lopeia JE, Correa G, Brazzini A, et al. Percutaneous transhepatic treatment of symptomatic mesenteric venous thrombosis. J Vasc Surg. 2002;36:1058–1067.
55. Direct vs indirect thrombolysis
• Indirect infusion of thrombolytics into SMA is technically less demanding but does
not allow direct infusion into the thrombus. As a result the thrombolytics have a
propensity to be diverted into the collaterals and prolong the total infusion into SMA.
• Prolonged catheterization may itself pose a risk of embolizing SMA and its arterial
branches itself.
• Direct access to portal vein via transjugular or percutaneous intrahepatic route targets
the thrombus directly and improvement in flow and clinical symptoms.
• It also has the advantage of being less time consuming, more efficient and reduced
dose of thrombolytics thereby reducing the thrombolysis related complications.
56. Thrombectomy
• Surgical thrombectomy is associated with recurrence of thrombosis, surgical morbidity and
mortality and hence not recommended.
• Mechanical thrombectomy by percutaneous trans-hepatic route has the advantage of
rapidly removing thrombus in a recently developed PVT (<30 days) although its drawbacks
include intimal or vascular trauma to the portal vein, that may promote recurrent
thrombosis.
• Balloon dilation and placement of vascular stent are helpful in decreasing the risk of
recurrent thrombosis where a defective surgical technique is the reason for thrombosis.
57. TIPS in PVT
• Transjugular intrahepatic portosystemic shunt (TIPS) insertion for the treatment of
portal hypertension–related complications has been reported to be feasible in
patients with a cavernoma when intrahepatic portal veins are visible.
• Hepatic encephalopathy may be seen in 4–27% and TIPS dysfunction in 20–38% of
patients.
• TIPS is unsuccessful if the lumen of thrombosed portal vein is not catheterizable
and cavernomatous vein is not amenable to dilatation.
58. Surgery
• Intestinal Resection
• When intestinal infarction is suspected, laparotomy for an exploration of intestinal
viability and a resection of necrotic parts is indicated.
• The challenge is to preserve as much viable bowel as possible so as to avoid short
bowel syndrome.
• Partial intestinal resection may also be indicated in patients with occlusion related to
post-ischemic stenosis.
59. • Decompressive Surgery
• Shunt surgery - Rex shunt (mesenteric left portal by pass), can be considered in the
patients with recurrent bleeding despite endoscopic and pharmacologic therapy, or with
severe portal cavernoma cholangiopathy. (avoided in cirrhotics)
• It is generally accepted that only widely patent superior mesenteric or splenic veins are
suitable for effective portosystemic shunting.
• Splenectomy can be done to treat symptomatic hyper-splenism.
Surgery
60. Management of Portal Cavernoma Cholangiopathy
• Specific treatment of portal cavernoma cholangiopathy should be considered only in
patients with jaundice, pruritus, or cholangitis.
• Bile stones can be extracted endoscopically. Biliary strictures can be treated with repeated
temporary stenting.
• A risk of bleeding from bile duct varices should be kept in mind.
61. Pregnancy and PVT
• In a study of 45 pregnant PVT patients treated with anticoagulation, the rate of
miscarriage was 20%, and preterm birth occurred in 38% of patients. However, fetal and
maternal outcomes were favorable for most pregnancies.
• Thus pregnancy should not be contraindicated in women with stable PVT.
• Anticoagulation therapy should be maintained during pregnancy if there is an underlying
pro-thrombotic condition.
Hoekstra J, et al: Pregnancy in women with portal vein thrombosis: results of a multicentric European study on maternal and fetal management and outcome. J Hepatol 57:1214–1219,
2012.
62. • The indication for (and intensity of ) anticoagulation therapy in women with PVT
and no identified risk factor is unclear, and should be discussed on a case-by-case
basis.
• Vitamin K antagonists are associated with a high rate of congenital malformations.
Therefore it is recommended to switch from a vitamin K antagonist to low molecular
weight heparin as early as possible.
Pregnancy and PVT
64. Epidemiology
• Cirrhosis accounts for approximately one third of unselected cases of PVT.
• The estimated prevalence of PVT in patients with cirrhosis ranges from 0.6% to 26%.
• In a recent cohort study of more than 1200 patients, most with compensated cirrhosis at
the baseline, the incidence of PVT was 5% and 11% at 1 year and 5 years, respectively.
(increases with the severity of liver disease)
Nery F, et al: Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study. Hepatology 61:660–667, 2015.
65. • In addition to cirrhosis, PVT is common with hepatobiliary cancers.
• For hepatocellular cancer (HCC), 23% and 44% of untreated and autopsy series of
patients were found to have PVT, respectively.
• HCC alone confers >100-fold risk of PVT over that for the general population.
Epidemiology
Amitrano L, Brancaccio V, Guardascione MA, Margaglione M, Iannaccone L, D'Andrea G. Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatology.
2000;31:345–348.
66. Natural history of non-tumorous PVT in cirrhosis
Sarin et al. Gastroenterology
2016;151:574–577
67. Various classification system of PVT in cirrhosis
• Stieber Classification (1991) – First classification
• Nonami Classification (1992)
• Yerdel Classification (2000) – Used for liver transplant
• Jaimeson Classification (2000)
• Bauer et al (2006)
• Shie et al (2011) – Used for malignant PVT in cirrhosis
• Jingqin Ma et al (2014)
• Baveno VI – Classification (2015)
68. Anatomico-Functional Classification of PVT in Cirrhosis
(BAVENO VI 2015)
Asymptomatic (AS)
Symptomatic (S)
Importance
• Defined acute and chronic thrombosis
• Etiology and underlying disease included
• Degree of occlusion and presence or absence of
blood flow included; response to therapy can be
monitored
• Useful for treating clinicians, surgeons and
radiologists
69. Examples (defining PVT in cirrhosis)
• Case 1: a patient with cirrhosis is incidentally found to have a new and complete
occlusion of the main portal vein trunk, with no evidence of bowel ischemia.
• Patient would be designated as PVT type 1, occlusive, recent, and asymptomatic.
• The first section describes anatomic and the later 3, the functional aspects of PVT.
• One may depict these by using letters as well: PVT-I, ORAs
70. • Case 2: a cirrhotic patient who presents with features of acute abdominal pain, and
on contrast-enhanced computed tomography examination has total occlusion of
both the branches of the portal vein with the thrombus extending into the
mesenteric vein along with bowel ischemia.
• The diagnosis is PVT type IIb, occlusive, recent, symptomatic with acute with bowel
ischemia or PVT type IIb, ORSAbi with possible mesenteric extension.
• The other variables such as the extent and the nature of underlying liver disease
could be added to the classification, if necessary.
Examples (defining PVT in cirrhosis)
71. Etiology
• Cirrhosis is no longer considered a hypo-coagulable state.
• In fact the pro-coagulant and anticoagulant factors are in a state of balance in cirrhosis
with no increased bleeding risk. Instead, increased factor VIII levels, reduced albumin tilt
the balance towards hypercoagulability in cirrhosis.
• In patients with cirrhosis, studies evaluating an association with pro-thrombotic disorders
have yielded inconsistent results.
• Among the patients of cirrhosis, obesity and diabetes, were found to be associated with
the occurrence PVT. PVT development has been linked with decrease in portal flow
velocity.
72. Proposed Parameters for Predicting Pretest Probability of PVT in
Cirrhosis
Major Characteristic Minor Characteristic
Child’s class B or C cirrhosis
Prior history of resolved PVT
Associated prothrombotic risk
factors – factor V LM,
prothrombin gene mutation,
MTHFR mutation.
Evidence of a large portosystemic shunt, large IGV1
Active hepatocellular malignancy
History of/or active systemic venous thrombotic events or abortions
Clinical symptoms and signs of acute abdomen
New onset or worsening portal hypertension complications
Recent abdominal interventions – endoscopic, radiological or surgical
Portal flow velocity < 15 cm per second at any time during prior Doppler
evaluations
Sarin et al. Gastroenterology
2016;151:574–577
Presence of 2 major, 1 major and 2 minor, or 4 minor criteria can give a high
probability for the development or pretest probability of the presence of PVT in a
cirrhotic patient.
73. Clinical and Laboratory Features
• PVT in patients with cirrhosis is found in the absence of recent signs and symptoms
in more than 40% of cases.
• The most common concurrent manifestations are variceal bleeding and ascites.
• When the thrombus extends to involve the superior mesenteric vein, PVT is usually
symptomatic, with manifestations ranging from mere abdominal pain to intestinal
infarction.
• In patients with cirrhosis and portal venous obstruction, invasion by hepatocellular
carcinoma should be ruled out before making a diagnosis of bland thrombosis.
74. Imaging Features
• PVT is frequently recognized on imaging for unrelated reasons, particularly the screening
patients for hepatocellular carcinoma.
• Duplex ultrasonography appears to be highly accurate. CT or magnetic resonance
angiography is useful to evaluate thrombus extent.
• Partial (and thus non-occlusive) PVT is the most commonly observed feature, in 43% to
75% of patients with PVT.
• Tumor invasion of the portal vein by hepatocellular carcinoma should be considered in all
patients with an obstructed portal vein.
75. Ultrasound and color Doppler findings in patient with liver cirrhosis and portal vein
thrombosis. Portal thrombosis represented by the presence of echogenic material
inside the portal vein on gray-scale; flow revealed on the periphery of the vessel.
76. Outcome
• Compared with control patients, PVT is more common in candidates for liver
transplant, large esophageal varices, higher MELD score, low platelet count and
low prothrombin time.
• Recent longitudinal studies found that the development of PVT was not associated
with subsequent progression of liver disease, although it was associated with a
poorer outcome after liver transplantation.
• These findings suggest that the development of PVT is a marker of the severity of
cirrhosis rather than a direct cause of the progression of liver disease.
Englesbe MJ, et al: Portal vein thrombosis and liver transplant survival benefit. Liver Transpl 16:999–1005, 2010
77. Variant of PVT Differentials Differentiating features
PVT in cirrhosis PVT (bland thrombosis)
PV invasion by HCC
(in cirrhosis)
CT shows non-enhancing filling defect in the
background of cirrhotic Liver
CT shows filling defect with rim enhancement
of vessel wall (due to malignant invasion),
disruption of vessel wall, expansile effect due to
tumor mass and tumor itself also (with or
without underlying cirrhotic liver)
D/D for variants of PVT
78. Management
Algorithm for the management
of anticoagulation therapy in
patients with PVT and
underlying cirrhosis.
ZAKIM
81. Anticoagulation
• The aims of anticoagulation are to permit/facilitate liver transplant and to reduce post-
transplant mortality and morbidity and also to prevent recurrence of thrombosis.
• Anticoagulation therapy appears to be safe in these patients.
• Low molecular weight heparin appears to be safe.
• The alternative option consists of oral vitamin K antagonists, aiming at an international
normalized ratio of 2 to 3.
82. Role as Prophylactic Anticoagulation to Prevent Portal Vein
Thrombosis
• Low molecular weight heparin has been shown to prevent PVT and liver decompensation
in patients with advanced cirrhosis in a recent randomized controlled trial.
• Enoxaparin (4000 IU/day, subcutaneously for 48 weeks) was effective in preventing PVT
in cirrhosis with Child score 7–10 such that no patient in enoxaparin group developed
PVT compared to placebo group (16.6%).
• Liver decompensation was less in enoxaparin group (11.7%) than controls (59.4%).
Enoxaparin was safe with no significant side effects or hemorrhagic events.
Villa E, Camma C, MariettaM, Luongo M, Critelli R, Colopi S. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis.
Gastroenterology. 2012;143:1253–1260.
It is too early to recommend anticoagulation for a
prophylactic role in preventing PVT due to limited
data availability.
83. TIPS
• TIPS is feasible in 73% to 100% of patients with PVT as long as intrahepatic
branches of the portal vein are visible.
• In the reported studies, the indications for TIPS insertion consisted of refractory
complications of portal hypertension, not PVT by itself.
• TIPS insertion might be considered in patients with thrombus extension receiving
anticoagulant therapy, with recurrent or refractory bleeding, or with refractory ascites.
84. PVT in HCC (Portal vein tumor thrombosis)
• HCC is prone to invading the portal venous system.
• Approximately 10%–40% of patients exhibit macroscopic PVTT when HCC is first
diagnosed.
• The incidence of micro-PVTT is even higher and is present in 20% of tumors with
diameters of 2 cm, 30%–60% in tumors with diameters of 2–5 cm, and 60%–90% in
tumors with diameters of > 5 cm.
86. Mechanism of PVTT formation/Biomarkers
• As the majority of PVTT emerges around the primary tumor (aPVTT), the traditional
belief is that PVTT develops following the direct invasion of a liver tumor, resulting in a
hepatic artery-portal vein fistula and portal vein countercurrent.
• Abnormalities in coagulation and fibrinolysis systems and angiogenesis, as well as in
many adhesion molecules and chemokines, are associated with PVTT formation.
Cut-off value of >20, 000 ng/mL for α-fetoprotein has a specificity of 96% and a sensitivity of
only 76%.
Other potential biomarkers include des-gamma-carboxy prothrombin (DCP), thrombus
precursor protein, and alfa-l fucosidase.
87. Therapeutic interventions for PVTT
• EASL – Sorafenib
• APASL –
• Surgery - resection of both hepatic tumors and PVTT.
• TACE - can be performed safely and feasibly in select patients with good liver
function and adequate collateral circulation around the occluded portal vein
regardless of PVTT extent. However, no complete remission (CR) has been reported
after TACE.
• The reported median survival time for patients with all PVTT types who received
TACE is between 5.6 and 8.7 months.
88. • RT - In the past, radiation was rarely used alone and was usually combined with TACE or
other treatments given the liver’s low tolerance to external RT.
• The rapid progress in RT techniques has enabled the delivery of high radiation doses to
HCC and PVTT without significantly increasing radiation toxicity.
• Reported RT doses vary from 17.5 Gy to 60 Gy in the 1.8–4.5 Gy fraction with response
rates of 27.9%–53.8%.
• The median survival time for responders and non-responders was 10.7–22 and 5–7.2
months, respectively.
Therapeutic interventions for PVTT
89. • Transarterial radio-embolization (TARE)
• TARE is a special type of TACE utilizing iodine-131-labeled lipiodol (131I) or
yttrium-90 (90Y) as a cytotoxic agent in the hepatic artery.
• The response rate is 28%–50%, and the median survival time is 3.2–10.4 months for
patients with all PVTT types.
Therapeutic interventions for PVTT
90. Difference between PVT and PVTT
PVT PVTT
Seen as a low density,
non-enhancing defect within portal veins
Enhances following contrast administration
Non-occlusive Occlusive
Expansive effect (portal vein enlargement due
to the mass forming thrombus)
Disruption of the vessel wall and intra
thrombus arterial neovascularization.
Associated with non-cirrhotic or cirrhotic liver Associated with primary malignancy
Thread and streak sign (arteriography)
