A relatively common complication in liver cirrhosis, but might also occur in absence of an overt liver disease.
Several causes, either local or systemic, maybe present to account for pathogenesis.
No single factor may be identifiable.
Portal vein thrombosis (PVT) refers to the complete or partial obstruction of blood flow in the portal vein, due to the presence of a thrombus in its lumen.
It is the most common thrombotic complication in patients with cirrhosis with an annual incidence of 4.6–12.8%, and the prevalence of up to 26% in liver transplant candidates.
Classified into four categories, depending on the extension of the thrombosis (1) confined to the portal vein beyond the confluence of the splenic vein (2) extension to the superior mesenteric vein, with patent mesenteric vessels (3) extension to the whole splanchnic venous system, with large collaterals (4)) with only fine collateral vessels
The above classification provides information about patient’s operability and clinical outcome.
With thrombotic extension to both portal and mesenteric veins, the risk of bowel ischemia and mortality is high.
Prevalence among cirrhotic patients ranges between 4-15%, and is responsible for about 5%-10% of cases.
Clinical presentation is different in acute or chronic onset and depends on the development and the extent of a collateral circulation.
With acute PVT Intestinal congestion, ischemia, abdominal pain, diarrhea, rectal bleeding, abdominal distention, nausea, vomiting, anorexia, fever, acidosis , sepsis and splenomegaly are common features of acute PVT.
In chronic PVT patients may be asymptomatic, or manifest with splenomegaly, pancytopenia, varices, and, ascites.
The etiology of PVT cannot be identified in approximately 15-30% of patients.
The presence of portal hypertension, requires the consideration of PVT, especially in cirrhotic patients.
Early diagnosis and appropriate management of secondary portal hypertension may be life-saving.
Associated with PVT the liver loses about two thirds of its blood supply, yet such a process is usually well tolerated due to vasodilation of the hepatic artery preserving liver function, and rapid development of collaterals to bypass the obstruction.
Associated with an increased risk of uncontrolled variceal bleeding, and when complete or extended to the superior mesenteric vein, is associated with a higher mortality after liver transplantation.
Vascular neo-formation begins a few days after portal vein obstruction, and is completed within 3 to 5 weeks.
An incidental finding in about 1% of the general population.
About 6.5% in patients with a hepatocellular carcinoma have PVT at the time of diagnosis.
Abdominal inflammation due to appendicitis, diverticulitis, inflammatory bowel disease, pancreatitis, cholecystitis, hepatic abscesses, and cholangitis, liver cirrhosis or tumors, are the most common local thrombotic risk factors.
Malignancies, frequently of hepatic or pancreatic origin, are responsible for 21%-24% of overall cases of PVT, and vascular invasion, compression by tumor or a hypercoagulable state are the mechanisms involved in neoplastic PVT development.
PVT risk with cirrhosis is related to the severity of the disease, with the prevalence ranging from 1%, at early stage to 30% in candidates for liver transplantation.
With a hepatocellular carcinoma, the incidence of PVT rises to 10%-40%.
PVT may be secondary to local adenopathy, systemic inflammatory response syndrome, surgical trauma to the portal venous system as seen with portosystemic shunting, splenectomy, liver transplantation, chemoembolization therapy for malignancy, and fine needle biopsy of abdominal masses.
Myeloablstive disorders and prothrombotic have a prevalence of about 40% and 60%, respectively.
Factor V Leiden mutation is the most common thrombophilia predisposing to PVT, followed by protein C deficiency.
Among the other thrombophilic disorders, a prothrombin gene mutation is frequent among cirrhotics with PVT.
Presence of anticardiolipin antibodies is seen frequently in patients with chronic liver disease, and may be associated with thrombotic events, such as PVT.
PVT is a manifestation of a myeloproliferative disease in 22-48% of patients.
When PVT presents as a sole finding an overt myeloproliferative disorder may develop in greater than 50% of cases.
The 1849G→T point mutation in the gene encoding tyrosine-protein kinase JAK2, is a specific and easily detectable marker for myeloproliferative diseases which can often be useful for a rapid diagnose in PVT patients.
When the cause for a PVT is not recognized the clinical course is generally favorable, with a low incidence of complications.
PVT development is complex and multifactorial.
Acute PVT is associated with intestinal symptoms of ; abdominal pain, distention, diarrhea, rectal bleeding, nausea, vomiting, anorexia, fever, splenomegaly and sepsis with lactic acidosis,
In acute PVT perforation, peritonitis, shock, and death from multiorgan failure might occur.
On physical examination, the abdomen might be distended, guarding is rare, and the majority exhibit splenomegaly.
Ascites is rare in acute PVT.
Chronic PVT can be nearly asymptomatic, except for the presence of varices, cutaneous collateral blood vessels or ascites.
Patients with chronic thrombosis do not usual recognize any previous trigger event or disease.
The majority of patients with chronic PVT develop esophageal varices,
Gastrointestinal bleeding is reported as the first presenting symptom in about 20%-40% of cases of chronic PVT.
All patients with PVT should undergo endoscopic exam to evaluate the presence of varices.
In cirrhotics with PVT, the risk of variceal bleeding is nearly 80-120 times higher than in patients without liver disease,
Hypersplenism and pancytopenia, are commonly present in chronic PVT.
If one branch of the portal vein is preserved in PVT, portal pressure may be normal, and hypersplenism/pancytopenia may not be present.
Ascites and encephalopathy are uncommon and if present only transient in chronic PVT.
Extrahepatic biliary tree abnormalities occur in more than 80% of patients with chronic PVT and include compression by varices and pericholedochal fibrosis.
A pseudocholangiocarcinoma sign caused by the displacement, strictures or thumbprinting of the biliary ducts produced by neo-formed vessels is present in approximately 80% of PVT patients at endoscopic retrograde cholangiopancreatography, mimicking a cholangiocarcinoma.
Usually recognized at an early stage often based on the incidental finding of hypersplenism or signs of portal hypertension.
Ultrasonography is usually the initial imaging technique, with a sensitivity and specificity ranging between 60% and 100%.
Ultrasound may reveal the presence of solid, hyperechoic material in distended portal vein, with the presence of collateral vessels.
Endoscopic ultrasound is 81% sensitive and 93% specific in diagnosis.
Endoscopic ultrasound cannot investigate the distal superior mesenteric vein and the intrahepatic portion of the portal vein due to technical reasons.
CT scanning and magnetic resonance imaging (MRI) are able to demonstrate hyperattenuating material in the portal vein lumen and the absence of enhancement after contrast injection.
CT abdomen useful for the identification of the possible cause of the thrombosis or potential complications, such as bowel ischemia and perforation.
MRI may confirm vascular occlusion.
Contrast-enhanced MR angiography allows assessment of the flow direction in the portal venous system and can determine its patency, helps to determine the presence of varices.
MRA can evaluate the function of surgical shunts.
In PVT patients, liver function is typically normal, unless comorbidities liver disease exists.
Prothrombin and other coagulation factors could be moderately decreased, while D-dimer is usually increased.
As PVT is considered a part of the natural history of liver cirrhosis, its prevention is the first aim in the management of patients with an advanced liver disease.
The strongest predictive factors for PVT development in cirrhotic patients are male gender, previous surgery or interventional treatment for portal hypertension, previous variceal bleeding, thrombocytopenia, and liver failure.
A portal flow velocity below 15 cm/s, as determined by ultrasound is a predictor of PVT development.
In establishing a diagnosis of PVT local causes such as cirrhosis, malignancies, pylephlebitis, liver cysts, vascular abnormalities, and pancreatitis have to be excluded.
If no local factor is found to account for PVT, the presence of a thrombophilic disorder must be investigated.
In the absence of a local cause or a propensity for thrombosis, the PVT should be considered to be idiopathic.
A subclinical prothrombotic state has been reported in about 70% of idiopathic PVT cases and may be related to an overt or occult myeloproliferative disease.
The degree of the obstruction of the portal vein should be investigated.
A partial thrombosis of the portal vein is associated with few symptoms.
Rapid onset and complete obstruction of the portal or mesenteric vein induces intestinal congestion, manifested by a diffuse thickening of the intestinal wall.
Liver function is usually preserved, probably because the increased hepatic arterial blood flow supplants portal obstruction.
Collateral circulation develops rapidly from pre-existing veins in the porta hepatis within 2 to 3 d after the onset of acute thrombosis.
Spontaneous recanalization occurs in approximately 1/3 of patients.
For patient who receive anticoagulation there is a higher recanalization rate and reduced progression of thrombosis, without increased risk of bleeding.
The prognosis for patients with non-cirrhotic and non-neoplastic PVT is generally good, while in other situations the outcome is related to the underlying liver disease.
The mortality rate is less than 10% in PVT of chronic onset, except for patients with malignancy or cirrhosis where it as high as about 25%.
Advanced age, malignancy, cirrhosis, mesenteric vein thrombosis, absence of abdominal inflammation, and increased serum levels of aminotransferase and decreased albumin are associated with reduced survival.
Myeloproliferative disorders do not to affect short-term survival.
Acute PVT, when recognized and treated before the occurrence of intestinal infarction is associated with a good prognosis, while patients with bowel ischemia and multiorgan failure the mortality rate is approximately 20%-50%.
PVT is an indication for liver transplantation.
The rate of thrombosis recurrence with hepatic transplantation estimated within 9% to 42%, and male gender, previous treatment for PVT, Child-Pugh class C, and alcoholic liver disease are associated with higher risk.
Patients with an obstruction of more than half of the portal vein have increased risk of peri-operative complications, higher mortality, and decreased long-term survival after hepatic transplantation.
In cirrhotics with PVT, the liver transplantation procedure may be more difficult, often complicated by rethrombosis and reintervention, but with the same morbidity and mortality of non-cirrhotic patients.
PVT development is a rare after liver transplantation with an incidence ranges between 1% and 2%.
Management is mandatory to resolve portal vein obstruction and avoid serious complications.
Treatment is similar in acute and chronic PVT: consisting in correction of causal factors, prevention of thrombosis extension, and achievement of portal vein patency.
In the presence of long standing thrombosis, the management of complications related to portal hypertension and portal cholangiopathy have to be concurrent.
Anticoagulant therapy is the best way to obtain portal vein recanalization, and other modalities of treatment utilized in case of partial or absent PVT resolution.
Anticoagulation is utilized in acute PVT, but there is no randomized controlled trial regarding its use.
Fondaparinux and low molecular weight heparin are both effective drugs for the treatment of portal vein thrombosis in patients with cirrhosis.
In about 10% of cases, PVT is resistant to anticoagulants.
When intestinal infarction occurs, anticoagulants administered prior to laparotomy benefits survival.
In acute PVT the sooner the anticoagulant therapy is given the better the outcome: the rate of recanalization is about 69%, if anticoagulation is instituted within the first week after diagnosis, and it falls to 25% when instituted at the second week.
Anticoagulation in chronic PVT is controversial and more variable.
Anticoagulant treatment is administered to only 30% of patients with chronic PVT.
Use of anticoagulants is less in chronic PVT due to concerns about the presence of gastro-esophageal varices, low platelet counts, and coagulation dysfunctions
Anticoagulants are effective in preventing new thrombotic events with a low mortality.
If thrombosis is recent anticoagulation should be administered for 3-6 mo, as a complete portal vein recanalization can be delayed.
Long-term use of anticoagulants in cirrhotic patients is reserved for patients with intestinal ischemia or infarction, or who have an underlying pro thrombotic disorder.
Cirrhosis patients with PVT should have prophylactic therapy for variceal bleeding.
Thrombolytic therapy is effective treatment to recanalize in acute PVT, but less than with conservative management and with a higher mortality.
Thrombolytic therapy can be given into the systemic venous circulation, the superior mesenteric artery, or the portal vein.
Despite the high incidence of side effects, thrombolysis should be considered when initial anticoagulant therapy fails.
Surgical thrombectomy is usually not recommended, as high morbidity and mortality are associated.
Percutaneous transhepatic mechanical thrombectomy may be effective in recent thrombosis, but vascular trauma can occur.frequent and cause rethrombosis.
Transjugular intrahepatic portosystemic shunt placement, is reserved for patients with acute PVT before or after liver transplantation, or in alternative to thrombolysis when anticoagulation fails.
A distal splenorenal shunt may be applied as the last choice, and only in absence of splenic or superior mesenteric vein thrombosis.