Splanchnic Venous Thrombosis

Etiology

Left-sided portal hypertension results from complete obstruction of the splenic vein; this does not occur in all cases due to anatomic variants as 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 picks up this disease as a confirmation of clinical judgment or sometimes incidentally. Results from one study in Sweden noted an increase from 2 to 2.7 cases 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% for portal vein thrombosis. In contrast, the autopsy of patients who died of cirrhosis has reported a prevalence of 6% to 64%. The prevalence is unknown in individuals who are non-cirrhotic.[3]

Chronic pancreatitis is the most common reason for splenic vein thrombosis. Splenic vein thrombosis was reported in 11% of the results from a study and 5% to 22% of patients with chronic pancreatitis in another study.[4] Gastric variceal bleeding is the initial presentation in between 45% to 72% of patients with splenic vein thrombosis. Some study results have shown that acute mesenteric venous thrombosis is the cause of acute mesenteric ischemia in 2% to 10% of the cases.[5] Two reviews have reported that of all cases of mesenteric venous thrombosis, only 24% to 40% were chronic mesenteric venous thrombosis. Chronic mesenteric venous thrombosis is noted less than acute thrombosis because of lower incidence or 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 produced results showing an incidence rate of 2.2 and 2.0 per million in women and men, 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 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 increased 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 an 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 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 imaging.[9] Acute hepatic venous thrombosis presents with fever, abdominal pain, and jaundice, with or without hepatic encephalopathy. In contrast, 15% to 20% 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 right upper quadrant abdominal pain cases, the first study to perform is typically a Doppler ultrasound, which is less costly and more comfortable than a CT scan or magnetic resonance imaging (MRI). In portal vein thrombosis, Doppler ultrasound shows hyperechoic material in the portal vein. Based on the thrombus caliber, there could be a decrease or even no flow to the portal vein. The mesenteric or splenic veins 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 a 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 mostly used when planning 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 makes diagnosing splenic vein thrombosis highly improbable. In mesenteric venous thrombosis, study results have shown that a CT scan of the abdomen has 90% accuracy. In cases where a 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 MR venography.[9] Doppler ultrasound diagnoses hepatic venous thrombosis, and a CT scan of the abdomen or MRI confirms it. Doppler shows hyperechoic material in the hepatic vein and other findings such as hepatomegaly, ascites, or hepatic lobe atrophy.

Laboratory

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

Endoscopy

An upper endoscopy is needed in cases of hematemesis or upper gastrointestinal bleeding, as an endoscopy checks and confirms variceal bleeding. Patients with portal vein thrombosis and cirrhosis are 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 reduce mortality and morbidity. Treating the underlying cause, the thrombosis itself, and the complications that it causes, such as variceal bleeding is important. There is no consensus when treating splanchnic venous thrombosis. Results from 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; patients who are asymptomatic should not be treated.[12](A1)

By 1 estimate, about 25% of splanchnic vein thrombosis cases present with gastrointestinal bleeding at 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 weighed against the therapy benefits. Active bleeding is a contraindication for anticoagulation, but a history of previous bleeding is not.[14]

Study results have shown that patients with cirrhosis with portal vein thrombosis benefits 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. However, study results have not shown an increase in episodes of bleeding after anticoagulation therapy.[7](B2)

Low molecular weight heparin (LMWH) is the drug of choice for anticoagulation. Splanchnic vein thrombosis cases have an increased risk of gastrointestinal bleeding, and therefore, LMWH (with a shorter half-life than warfarin) is the preferred medication. Additionally, by 1 estimate, 22% to 27% 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 at least 3 months. A reason for stopping anticoagulation is a high risk of bleeding. Hypercoagulable states require more extended periods of treatment.[14](A1)

There are 2 studies providing results and several articles on using 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 cytochrome P (CYP)3A4 system.[17] (A1)

In cases of symptomatic splenic vein thrombosis, splenectomy is the best treatment. The role of splenectomy is unclear in patients who are asymptomatic. 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](B2)

Differential Diagnosis

Differential diagnosis to consider and rule out regarding splanchnic venous thrombosis include the following:

• 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, results showed fewer than 5% 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] Results from a study of 3700 patients with mesenteric vein thrombosis showed the mortality rate was 44% compared to a 66% 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; this does not occur in all cases due to anatomic variants. Many patients are asymptomatic, and 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.