Portal vein thrombosis (PVT) is a narrowing or blockage of the portal vein by a blood clot. Thrombosis can develop in the main body of the portal vein or its intrahepatic branches and may even extend to the splenic or superior mesenteric veins (SMV). PVT frequently occurs with cirrhosis of the liver. It may also occur without an associated liver disease like malignancy, abdominal sepsis, pancreatitis, etc. The terminology of Extra Hepatic Portal Venous Obstruction (EHPVO) should be considered as a separate entity which refers to the development of portal cavernoma or collaterals around chronic portal vein thrombosis.
The most common cause of PVT is cirrhosis. In a non-cirrhotic liver, PVT is mainly due to inherited or acquired pro-thrombotic states. Primary myeloproliferative disorders (MPD) are the most common procoagulant state found. Other pro-thrombotic conditions that cause PVT include paroxysmal nocturnal hemoglobinuria (PNH), antiphospholipid syndrome, hyperhomocysteinemia, inherited pro-thrombotic disorders such as protein C, S and antithrombin III deficiencies, and less frequently, factor V Leiden mutation, factor II mutation, and methylenetetrahydrofolate reductase (MTHFR) gene mutation. Rare conditions that are associated with PVT are pregnancy, chronic inflammatory diseases, oral contraceptives, and malignancies with or without the above prothrombotic causes. Malignancy is responsible for PVT in around 25% of cases.
The intra-abdominal inflammatory conditions leading vascular endothelial injury can cause PVT. These include pancreatitis, cholangitis, appendicitis, and liver abscess. Local injury to portal venous axis following splenectomy, laparoscopic colectomy, or abdominal trauma with the above acquired or inherited pro-thrombotic conditions can lead to PVT.
Etiology for EHPVO in children is phlebosclerosis with thrombosis as a secondary event. Omphalitis, neonatal umbilical sepsis, umbilical vein cannulation, repeated abdominal infections, sepsis, abdominal surgery, and trauma later progress to EHPVO.
The prevalence of PVT in cirrhosis has been reported to be 0.6% to 16%, and more commonly reported in patients awaiting liver transplantation. PVT is seen in up to 35% of cirrhotic patients with hepatocellular carcinoma. The lifetime risk of PVT in the general population is reported to be 1%.
The pathophysiology of portal vein thrombosis encompasses one or more features of Virchow's triad, which includes reduced portal blood flow, a hypercoagulable state, or vascular endothelial injury.
A confluence of splenic and superior mesenteric veins forms a portal vein, which carries blood from the spleen and small intestine to the liver. Patients with cirrhosis usually have slow blood flow through the severely scarred liver. Theses altered portal hemodynamics more likely to produce clot and can cause portal vein thrombosis.
Malignant portal vein obstruction is seen by direct vascular invasion by hepatocellular carcinoma, and cholangiocarcinoma or compression by tumor mass or lymph node are the other mechanisms involved.
Portal vein thrombosis is asymptomatic in a majority of patients. Clinically PVT may be acute or chronic, although no time frame exists to distinguish acute from chronic PVT. Portal hypertension develops as a result of chronic obstruction to flow within the portal venous system. Portal hypertension can present with left upper quadrant abdominal fullness due to splenomegaly or upper gastrointestinal (GI) bleeding from esophageal or gastric varices.
Non-cirrhotic non-malignant acute PVT usually presents with abdominal pain (91%), fever (53%) and ascites (38%). Extension of portal vein thrombus into a superior mesenteric vein may lead to intestinal ischemia, bowel infarction, ileus presenting as hematochezia, fever, and sepsis and is responsible for high mortality in this subset of patients.
If new portal vein thrombosis develops in people with cirrhosis, they present with hepatic decompensation in the form of ascites, jaundice or variceal bleeding. In patients with underlying cirrhosis, ascites usually develop when large amounts of fluids are given intravenously to treat massive bleeding from ruptured esophageal or gastric varices.
Patients with EHPVO present with only portal hypertension-related complications like a well-tolerated upper GI bleed, splenomegaly, anemia, and thrombocytopenia or may be asymptomatic with incidental detection following an imaging procedure.
Liver Function Tests
The liver functions are normal or near normal except if PVT occurs in a patient with cirrhosis. Portal hypertension due to chronic PVT may cause thrombocytopenia due to splenomegaly. Patients with portal biliopathy may show a rise in alkaline phosphatase and bilirubin.
Doppler ultrasound is an investigation of choice with sensitivity and specificity ranging from 80% to 100% with an accuracy of 88% to 98%. It will show solid isoechoic or hypoechoic material within portal vein either filling the lumen partially or completely with the absence or reduced portal venous flow. Portal cavernoma will be seen as multiple tortuous small vessels replacing the portal vein suggestive of chronic PVT. Ultrasound will also pick up associated with splenomegaly. Contrast-enhanced ultrasound (CDUS) and endoscopic ultrasound are other modalities that have been found to be superior to ultrasound in demonstrating the presence or absence of flow in portal vein when it is very small.
Computed Tomography and Magnetic Resonance Imaging
CT and MRI provide additional information such as the extension of thrombus, evidence of bowel infarction and status of adjacent organs. CT scan with contrast also helps to distinguish bland thrombus from the malignant one. Bland thrombus is typically seen as a low density, non-enhancing defect within portal veins, while a tumor thrombus enhances following contrast administration with distension of vessel wall or intra-thrombus contrast enhancement due to neovascularization. The sensitivity and specificity of MRI for detecting the main PVT are 100% and 98%, respectively. It is valuable in determining the resectability of neoplasm involving the portal venous system and follow-up after therapeutic procedures.. PET CT also has been shown to be helpful in differentiating benign and malignant portal vein obstruction.
This is invasive, but now an obsolete procedure is done in the past which involves injecting dye in the splenic pulp and visualizing the splenoportal venous axis. It helps not only in diagnosing PVT but also identifying the patency of splenoportal axis for future splenorenal or mesocaval shunt surgery. In the pre-US/CT/MRI era, it was proved to be a safe procedure which also helped in measuring portal pressure.
It is important to have an endoscopy in patients with PVT as portal hypertensive gastropathy is often present in the acute PVT with cancer or cirrhosis, while large ectopic/esophageal/gastric varices are present more often in patients with chronic PVT.
Once the diagnosis of PVT is made, the extensive investigation of prothrombotic disorders and local factors is recommended including antiphospholipid syndrome, protein C, S, antithrombin III levels, factor V, Leiden mutation, among others.
The aim of the treatment is to reverse or prevent advancement of thrombosis in the portal venous system and to treat complications of established PVT. There is a clear recommendation for the use of anticoagulation in non-cirrhotic acute PVT with good safety and efficacy data for both low molecular weight heparin new oral anticoagulants. However, the data in the setting of cirrhosis is limited. Anticoagulation is indicated with impending intestinal ischemia, decompensated liver disease awaiting liver transplantation, a compensated liver disease with a new diagnosis of acute PVT or PVT with asymptomatic mesenteric venous occlusion, while anticoagulation in non-transplant candidates with advanced liver disease and patients with portal cavernoma formation in the absence of thrombotic risk factors may not benefit survival. Enoxaparin was safe with no significant side effects or hemorrhagic events in cirrhosis. There is still not enough data with newer oral anticoagulants in cirrhosis as the majority are metabolized in the liver.
Thrombolytic therapy in very recent non-cirrhotic portal vein thrombosis can be done via indirect intraarterial infusion of tissue plasminogen activator, urokinase or streptokinase into the superior mesenteric artery (SMA) or directly via the catheter introduced into a portal vein either transhepatically or through transjugular approach. Prolonged catheterization of SMA may itself pose a risk of embolizing SMA and its arterial branches. Hence, direct access to portal vein via transjugular or percutaneous intrahepatic route is preferred mode as being less time-consuming and a more efficient technique with a requirement of a reduced dose of thrombolytics, thereby reducing the thrombolysis-related complications.
Surgical thrombectomy or mechanical thrombectomy by percutaneous transhepatic route is associated with recurrence of thrombosis from intimal or vascular trauma to the portal vein. Percutaneous transhepatic thrombo-aspiration within 72 hours has been done successfully in some patients.
Transvenous Intrahepatic Portosystemic Shunt
Transvenous intrahepatic portosystemic shunt (TIPS) placement in the setting of portal vein thrombosis is technically challenging for radiologists. However, when placed successfully, there is a possibility of achieving recanalization by disrupting the thrombus and mechanical thrombectomy.
In acute non-cirrhotic portal vein thrombosis with an early diagnosis with improved diagnostic techniques and use of early anticoagulation, the 5-year survival rate has now improved to 85%. The outcome of PVT is good, and mortality primarily is due to an underlying cause or as consequences of portal hypertension. Acute PVT usually has a good prognosis if it does not progress to intestinal infarction. In chronic extrahepatic portal vein thrombosis, bleeding-related mortality is much lower due to preserved liver function compared to cirrhosis. In contrast, portal vein thrombosis in a patient with cirrhosis, 2-year survival is reduced by 55% secondary to hepatic dysfunction.
Portal hypertension is responsible for the majority of the complications seen in patients with chronic PVT. It presents with splenomegaly, varices or ascites. Portal vein thrombosis commonly forms varices in sites other than the esophagus and stomach (ectopic varices).
Intestinal ischemia It is typically seen when acute PVT progresses to obstruction of mesenteric venous outflow with reflex arterial constriction and occlusion.
Septic Portal Vein Thrombosis
Septic portal vein thrombosis (acute pylephlebitis) occurs when PVT develops in a patient with an abdominal focus of an infection like appendicitis, diverticulitis, among others.
Portal cholangiopathy is a complication that may develop with longstanding PVT due to extrinsic compression of large bile ducts from venous collaterals around portal vein. It may progress to ischemic strictures of bile ducts presenting with obstructive jaundice and cholangitis.
Portal vein thrombosis is a relatively common presentation in clinical practice. Because the disorder has enormous morbidity and mortality if left untreated, the condition is best managed by a team of an interprofessional healthcare professionals. To reduce morbidity, prompt diagnosis and treatment are necessary. Patients treated with early anticoagulation have a 5 year survival of 85%. The acute condition has a much better prognosis than chronic portal vein thrombosis, where the liver function is often compromised. TIPS and open surgery procedures are much less used today because of availability of percutaneous techniques, which are associated with much fewer complications.
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