Continuing Education Activity

Blood clotting within the splanchnic veinous systems leads to splanchnic vein thrombosis. It includes thrombosis in the splenic vein, mesenteric vein, portal vein, or hepatic vein (Budd-Chiari syndrome). The most common site of venous thrombosis is a portal and mesenteric vein, with the least common being hepatic vein. Splanchnic venous thrombosis can lead to different symptoms depending on the site of the thrombosis. This activity reviews the evaluation and treatment of splanchnic venous thrombosis and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Identify the etiology of splanchnic venous thrombosis.
• Review the appropriate evaluation of splanchnic venous thrombosis.
• Outline the management options available for splanchnic venous thrombosis.
• Describe the interprofessional team strategies for improving care coordination and communication in splanchnic venous thrombosis to improve outcomes.

Introduction

Abdominal veins bring blood lacking in oxygen from the abdomen to inferior vena cava, which then drains to the right atrium. Abdominal organs have two venous systems, the systemic one which drains directly to inferior vena cava and the portal one which drains to the hepatic portal vein and then inferior vena cava through the liver.

The systemic venous system includes common iliac, lumbar, renal, right testicular/ovarian, right suprarenal, inferior phrenic, and hepatic veins. The portal venous system includes: right and left gastric, cystic, para-umbilical, splenic, inferior mesenteric (via a splenic vein), and superior mesenteric vein. The splenic and superior mesenteric merge to form the portal vein.

Blood clotting in these venous systems can lead to splanchnic venous thrombosis. It includes thrombosis in the splenic vein, mesenteric vein, portal vein, or hepatic vein (Budd-Chiari syndrome). The most common site of venous thrombosis is a portal and mesenteric vein, with the least common being hepatic vein.[1] Splanchnic venous thrombosis can lead to different symptoms depending on the site of the thrombosis.

Etiology

Left-sided portal hypertension results from complete obstruction of the splenic vein. It does not occur in all cases due to anatomic variants. Many patients are asymptomatic. Significant splenomegaly may be detected on imaging. The patient may present with typical signs of portal hypertension, including gastroesophageal varices, ascites, and splenomegaly, which cannot be attributed to hepatic disease.

Some of the complications of splanchnic venous thrombosis include gastrointestinal bleeding, esophageal or gastric varices, intestinal ischemia, anemia, thrombocytopenia, and infection.

Epidemiology

The incidence and prevalence of splanchnic vein thrombosis are on the rise. This pattern is partially attributed to the widespread use of computed tomography that will pick up this disease as a confirmation of clinical judgment or sometimes incidentally. One study in Sweden noted an increase from 2 to 2.7 per 100,000 between the 1970s and 2000s.[2]

The most common leading cause of portal vein thrombosis is liver cirrhosis. Among patients with cirrhosis, ultrasound has shown a prevalence of 5 to 24 percent for portal vein thrombosis. In contrast, the autopsy of patients who died with cirrhosis has reported a prevalence of 6 to 64 percent. The prevalence is unknown in non-cirrhotic patients. [3]

Chronic pancreatitis is the most common reason for splenic vein thrombosis. Splenic vein thrombosis is reported in 11 percent in one study and 5 to 22 percent of patients with chronic pancreatitis in another study.[4] Gastric variceal bleeding is the initial presentation in between 45 to 72 percent of patients with splenic vein thrombosis. 

Some studies have shown that acute mesenteric venous thrombosis is the cause of acute mesenteric ischemia in 2 to 10 percent of the cases.[5] Two reviews have reported that of all cases of mesenteric venous thrombosis, only 24 to 40 percent were chronic mesenteric venous thrombosis. Chronic mesenteric venous thrombosis is noted less than acute thrombosis because of lower incidence or due to a lack of symptoms.

Hepatic venous thrombosis is more predominant in women in their 30s or 40s in non-Asian countries. One study in Italy showed the incidence rate of 2.2 and 2.0 per million in females and males, respectively. In contrast, hepatic venous thrombosis is more common in men than in women in Asian countries.[6]  

History and Physical

Sudden abdominal pain is the most common presentation of acute splanchnic venous thrombosis. Pain is absent in most cases of chronic venous thrombosis. Instead, these chronic cases will present mostly with upper gastrointestinal bleeding secondary to varices.[7]

Specifically, patients with acute portal vein thrombosis usually present with severe abdominal pain and nausea in the absence of endoscopic findings. Chronic cases can have esophageal or gastric varices, which can lead to gastrointestinal bleeding. Splenomegaly, ascites, and palmar erythema are common in such cases. However, portal vein thrombosis can also be asymptomatic and can be discovered incidentally when a patient undergoes abdominal imaging for any other reason. Portal vein thrombosis can compress bile ducts and cause biliary symptoms due to cholangiopathy and present with fever, pruritus, jaundice, and right upper quadrant abdominal pain. Although portal vein thrombosis usually has regular liver function tests, hyperbilirubinemia, and an increase in alkaline phosphate levels can be present in cholangiopathy patients.[7]

Splenic vein thrombosis presents in most cases with gastric varices. If there are gastric varices but no esophageal varices, or if gastric varices are more prominent than esophageal varices, then splenic vein thrombosis should be suspected.[8] Patients with splenic vein thrombosis can be asymptomatic or can present with a variety of symptoms. These symptoms include abdominal pain, variceal bleeding, splenomegaly, and thrombocytopenia.

Acute mesenteric venous thrombosis can lead to mesenteric ischemia and intestinal infarction, which presents with sudden periumbilical abdominal pain out of proportion to the clinical exam. Abdominal distention might be present on physical exam, and occult blood test may be positive. Subacute mesenteric venous thrombosis can ensue when venous thrombosis is present, but there is also partial compensation through collateral vessels that allow for some circulation. Therefore, subacute thrombosis can last for days to weeks before any symptom is present. In these patients, the most common presentation is nonspecific abdominal pain. Chronic mesenteric thrombosis is usually asymptomatic and found accidentally on abdominal imagining.[9]

Acute hepatic venous thrombosis presents with fever, abdominal pain, jaundice, with or without hepatic encephalopathy. In contrast, 15 to 20 percent of patients with subacute or chronic hepatic venous thrombosis are asymptomatic.[10] In chronic cases, symptoms occur when the patient is cirrhotic. These symptoms include palmar erythema, spider angioma, ascites due to portal hypertension and esophageal varices. 

Evaluation

Imaging

Computed tomography (CT) is the diagnostic method of choice in splanchnic vein thrombosis. In cases of right upper quadrant abdominal pain, the first study to perform is typically a Doppler ultrasound. Doppler ultrasound is less costly and more comfortable to achieve than CT scan or magnetic resonance imaging (MRI).

In portal vein thrombosis, Doppler ultrasound shows hyperechoic material in the portal vein. There could be a decrease or even absence of flow to the portal vein, based on the thrombus caliber. The mesenteric or splenic vein can also be enlarged since they merge to make the hepatic portal vein. If portal vein thrombosis is strongly suspected, it is best to omit the ultrasound and start with a CT scan or MRI of the abdomen (CT scan is preferred over MRI).  CT scan of the abdomen shows thrombus as a densely packed vein. CT scan is also additionally beneficial since it shows other pathology that might be present such as a cancerous tumor. Another diagnostic tool for portal vein thrombosis is angiography. Angiography is not as frequently considered as a CT or MRI. It is a more invasive evaluation that is mostly used when planning for shunt surgery.[7]

Doppler ultrasound is the best initial diagnostic test in cases with a suspicion of splenic vein thrombosis when considering all these facts. A normal splenic vein doppler will make the diagnosis of splenic vein thrombosis highly improbable.

In mesenteric venous thrombosis, studies have shown that a CT scan of the abdomen has 90 percent accuracy. In cases where CT scan is nondiagnostic, it is suggested to do CT angiography. Magnetic resonance (MR) venography is the most reliable imaging for mesenteric venous thrombosis. However, most cases can be seen on a CT scan without the use of MR venography.[9]

Doppler ultrasound diagnoses hepatic venous thrombosis, and a CT scan of the abdomen or MRI will confirm it. Doppler shows hyperechoic material in hepatic vein and other findings such as hepatomegaly, ascites, or hepatic lobe atrophy.

Laboratory

It is essential to check for coagulation defects in anyone with thrombosis and, most specifically, patients with portal vein thrombosis without cirrhosis.

Endoscopy

An upper endoscopy is needed in cases of hematemesis or upper gastrointestinal bleeding. Endoscopy will check and confirm variceal bleeding. Patients with portal vein thrombosis and cirrhosis will be monitored for varices (esophageal or gastric) by endoscopy. This fact holds accurate about patients with splenic vein thrombosis.    

Treatment / Management

There are multiple steps when treating splanchnic venous thrombosis, all of which will reduce mortality and morbidity. It is imperative to treat the underlying cause, the thrombosis itself, and complications that it causes, such as variceal bleeding.

There is no consensus when treating splanchnic venous thrombosis. Small uncontrolled studies have shown that systemic anticoagulation improved survival and lowered recurrence.[11] American College of Chest Physicians recommends treating symptomatic patients with anticoagulation. Asymptomatic patients should not be treated.[12]

By one estimate, about 25 percent of splanchnic vein thrombosis cases present with gastrointestinal bleeding at the time of diagnosis.[13] These are usually from esophageal varices. The decision to treat with anticoagulation, therefore, should be individualized. Potential risks such as bleeding should be weight against the therapy benefits. Active bleeding is a contraindication for anticoagulation, but a history of previous bleeding is not.[14]

Studies have shown that patients with cirrhosis with portal vein thrombosis will benefit from anticoagulation therapy. They have a lower rate of variceal bleeding when treated. Isolated portal vein thrombosis without cirrhosis is not as clear of a scenario. Studies have not shown an increase in episodes of bleeding after anticoagulation therapy.[7]

Low molecular weight heparin (LMWH) is the drug of choice for anticoagulation. Splanchnic vein thrombosis cases have increased risk of gastrointestinal bleeding, and therefore LMWH (with a shorter half-life than warfarin) is the preferred medication. Additionally, by one estimate, 22 to 27 percent of patients with splanchnic vein thrombosis have underlying solid malignancy. LMWH is traditionally used more frequently and effectively than warfarin in cancer cases.[12] The duration of anticoagulation therapy depends on the underlying cause. All patients with splanchnic vein thrombosis should probably be anticoagulated for a minimum of 3 months. A reason for stopping anticoagulation is a high risk of bleeding. Hypercoagulable states require more extended periods of treatment.[14]

There are two studies, and several articles on the use of direct oral anticoagulant medications (dabigatran etexilate, rivaroxaban, apixaban, and edoxaban) in splanchnic vein thrombosis. Overall, there was an increased risk of gastrointestinal bleeding using rivaroxaban as compared to LMWH.[15][16] Furthermore, the use of direct oral anticoagulants is contraindicated in patients with an underlying liver impairment since their metabolism is through the CYP3A4 system.[17] 

In cases of symptomatic splenic vein thrombosis, splenectomy is the best treatment. The role of splenectomy is unclear in asymptomatic patients. Such patients have a low risk of bleeding and can be observed and treated with splenectomy if they become symptomatic.[8]

Patients with cirrhosis and portal vein thrombosis need screening for esophageal varices, even in the absence of bleeding. This is done by upper endoscopy to prevent future variceal bleeding. If esophageal varices were found during screening, the patient should be prophylactically treated with nonselective beta-blocker drugs.[7]

Differential Diagnosis

Differential diagnosis includes all the reasons for abdominal pain and occasionally the etiologies for gastrointestinal bleeding. 

• Arsenic toxicity
• Budd-Chiari syndrome
• Cirrhosis
• Congenital hepatic fibrosis
• Granulomatous hepatitis
• Hepatoportal sclerosis
• Primary biliary cirrhosis
• Sarcoidosis
• Schistosomiasis

Prognosis

Morbidity and mortality of splanchnic vein thrombosis have improved over the years with treatment. This is mainly due to earlier diagnosis and treatment of the condition.

In a study that followed 136 patients with chronic portal vein thrombosis for 5 years, fewer than 5 percent of patients died of complications of thrombosis, such as gastrointestinal bleeding. However, the mortality rate is higher in patients who have mesenteric vein thrombosis in addition to portal vein thrombosis.[11]

In a study of 3700 patients with mesenteric vein thrombosis, the mortality rate was 44 percent, compared to 66 percent mortality rate in arterial mesenteric thrombosis.[18] However, the mortality rate is higher in patients with intestinal infarction.[19]

Complications

Left-sided portal hypertension results from complete obstruction of the splenic vein.  It does not occur in all cases due to anatomic variants. Many patients are asymptomatic. Significant splenomegaly may be detected on imaging. The patient may present with typical signs of portal hypertension including gastroesophageal varices, ascites, and splenomegaly which cannot be attributed to hepatic disease.

Some of the complications of splanchnic venous thrombosis include; gastrointestinal bleeding, esophageal or gastric varices, intestinal ischemia, anemia, thrombocytopenia, infection.

Deterrence and Patient Education

This is a rare medical condition. Patient education will be beneficial.

Enhancing Healthcare Team Outcomes

A collaborative effort between the primary care, gastroenterologist, radiologist, surgeon, and hematologist is of the essence in recognizing and efficiently dealing with this rare entity. Lack of knowledge and understanding of the disease and its predisposing factors, as well as a lack of an interprofessional approach, will cause complications.