Portal vein obstruction is a common complication of several metabolic and autoimmune diseases. It is most commonly the result of thrombosis of the portal vasculature, but it can also result from malignancies. Due to the vast range of diseases that result in portal vein obstruction, understanding the common causes, pathophysiologies, and relevant management is key to treating patients suffering from this disease.
The causes of portal vein thrombosis can be divided into two categories; inherited and acquired.
Rare iatrogenic causes include bariatric surgery, radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), or fine needle aspiration of pancreatic cancer.
The prevalence of portal vein occlusion varies in different populations. In patients with cirrhosis or portal hypertension, it is estimated to be anywhere between 1.6% and 15.8%. The incidence is higher where the cirrhosis results from alcohol use disorder or Hepatitis B infection. The prevalence is as low as 1% in patients with compensated liver cirrhosis, while as high as 25% in patients awaiting a liver transplant. Possible causes for the higher incidence in liver transplant patients include advanced underlying disease, immobility due to possibly worse ascites, and a higher degree of imbalance of clotting factors.
The pathophysiology of the obstruction depends upon the cause. In liver cirrhosis patients, endothelial dysfunction is implicated along with an imbalance of coagulation factors leading to a net hypercoagulable state. Blood samples of cirrhotic patients have been found to have high quantities of thrombin.
Similarly, stasis or low portal velocity has also been found to have an association with portal vein thrombosis. There could be an associated link with the use of beta blockers, but the results of a study demonstrating this link are yet to be replicated.
In cancer patients, the obstruction can occur due to thrombosis (from stasis or hypercoagulability caused by cancer) or direct invasion from a growing tumor.
Patients typically present with signs of portal hypertension. Although individual presentations vary depending on the cause, patients commonly demonstrate:
Depending upon the severity of the disease, splenomegaly will present in about 75 to 100% of patients. In patients with liver cirrhosis as the primary cause, signs such as spider angiomata and palmar erythema may be evident. If there has been longstanding portal hypertension, collaterals might be clinically evident with caput-medusae (umbilical veins), hemorrhoids (rectal veins), or in patients presenting with upper gastrointestinal bleeding from enlarged esophageal veins (varices).
In cases where malignancies are the primary cause, either from thrombus formation or direct invasion, clinical manifestations of the neoplasm could be prominent. In cases of pancreatic carcinoma, fatigue and jaundice are usually present. Similarly, jaundice is also present in hepatocellular carcinoma and cholangiocarcinoma. In patients with jaundice, associated pruritis is a common finding as well.
When portal vein obstruction is suspected, several modalities can help confirm or exclude the diagnosis. The first line of investigation is Doppler ultrasound. Contrast-enhanced ultrasound seems to be superior to Doppler ultrasound for the characterization and further evaluation of portal vein obstruction.
Liver function tests are expected to be normal unless there is underlying liver disease. Other recommended blood tests should encompass extensive procoagulant factors workup, including antiphospholipid syndrome, protein C, S, antithrombin III levels, factor V, and Leiden mutation.
CT and MRI provide additional information such as the extension of thrombus, evidence of bowel infarction, and the status of adjacent organs. The sensitivity and specificity for MRI in detecting a primary portal vein thrombosis are 100% and 98%, respectively. MRI is valuable in determining the resectability of neoplasm involving the portal venous system and follow-up after therapeutic procedures.
Endoscopy is essential in patients with overt upper gastrointestinal bleeding and can be helpful in patients presenting with symptoms of gastritis. Esophageal varices are a common finding in patients with chronic portal vein obstruction. If identified early, esophageal varices can be cauterized or clipped to prevent potentially life-threatening hemorrhage.
Treatment of thrombosis in cirrhosis patients can present a significant challenge as balancing anticoagulation with the risk of bleeding can be problematic. The Anticoagulation Forum recommends that cirrhotic patients with portal vein thrombosis should undergo endoscopic screening of esophageal varices and, if indicated, banding treatment should precede low molecular weight heparin (LMWH) treatment.
Choosing the right anticoagulant for a patient is difficult as well, as each agent has its benefits and risks. As cirrhotic patients have a raised international normalized ratio (INR) at baseline, monitoring warfarin treatment can be challenging. Despite some disadvantages, LMWH and vitamin K antagonists have been successfully used to treat thrombosis in cirrhotic patients. According to the guidelines of the American Association for the Study of Liver Diseases, acute portal vein thrombosis should be treated for at least 3 months with LMWH and switched to oral anticoagulant agents after patient stabilization. One study demonstrated partial or complete recanalization rates of up to 60% in cirrhotic patients treated early with LMWH or vitamin K antagonists.
The use of vitamin K antagonists has been the object of study, but no target INR has been defined. The study quoted above used a target INR of 2.5 for the patient's using warfarin. However, no data yet suggests what the goal INR should be for PVT patients treated with warfarin. With LMWH being well-studied and not requiring monitoring, it might be the best option for some.
Despite the interest in direct oral anticoagulants (DOACs), there is insufficient data to recommend their use. There have been some in vitro and theoretical literature supporting their use, but studies establishing their safety and efficacy are lacking at the moment.
A transvenous intrahepatic portosystemic shunt (TIPS) is considered a highly effective and relatively safe treatment modality. In a recent study of 70 cirrhosis patients who received TIPS, partial and complete recanalization was found in 57% and 30% respectively. However, TIPS is associated with worse outcomes in liver transplant recipients. It is associated with increased post-transplant morbidity, graft loss, and mortality.
Other surgical modalities used in the treatment of portal vein occlusion associated with variceal bleeding include shunt surgery (such as splenorenal and mesogonadal) and the controversial Sugiura procedure. However, the Sugiura procedure is rarely an option.
One should keep in mind the possibility of liver nodules forming in patients undergoing shunt procedures. Such nodules are known to present in patients with congenital portosystemic shunts without liver disease.
For obstruction caused by local invasion, treatment of the underlying malignancy might be helpful. In patients with an obstruction due to pancreatic cancer, chemotherapy has led to recanalization and improvement in survival.
Since portal vein obstruction is more of a radiological than clinical diagnosis, it is less likely to be suspected in a patient without ample evidence. However, due to similar symptomatology or pathophysiology, the following differentials should be ruled out:
The overall prognosis is excellent, with 10-year mortality of 25% and an overall mortality rate of approximately 10%. In the presence of cirrhosis and malignancy, the prognosis is worse and is dependent upon the underlying condition.
Complications of portal vein occlusion include:
This can present in multiple forms, including ascites, variceal hemorrhage, or hypersplenism.
Usually seen in acute portal vein thrombosis, leading to blockage of blood flow from the mesenteries.
Worsening hepatic function
In patients with cirrhosis, portal vein obstruction can lead to worsening liver function.
Septic portal vein thrombosis can occur if there is a concurrent abdominal focus of infection (appendicitis, diverticulitis, etc.)
Villa et al., performed a randomized controlled trial to evaluate the safety and efficacy of enoxaparin in preventing portal vein thrombosis (PVT) in patients with advanced cirrhosis. They found that "In a small randomized controlled trial, a 12-month course of enoxaparin was safe and effective in preventing PVT in patients with cirrhosis and a Child-Pugh score of 7-10. Enoxaparin appeared to delay the occurrence of hepatic decompensation and to improve survival." However, these findings require replication in more substantial, multi-centered trials.
Patients who are at high risk for portal vein thrombosis should be educated about these possible complications and be told to report new symptoms which could lead to an early diagnosis.
Portal vein obstruction, especially in the form of thrombosis, is a relatively common problem (especially in patients with liver disease). High-risk patients should receive streamlined care for early diagnosis and treatment. If found on routine ultrasound scans, the risks and benefits of treatment should be discussed. Early treatment with anticoagulation or TIPS might lead to survival benefit for the patient.
Both the nurse and pharmacist, along with physicians, should educate the patient on the importance of compliance with the anticoagulants as part of an interprofessional team approach to portal vein obstruction. These patients also need to return to the clinic to ensure that the INR is in the therapeutic range.
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