Mesenteric Venous Thrombosis

Etiology

Hypercoagulable states are present in 60% to 75% of patients with mesenteric venous thrombosis. Often, an inherited or acquired thrombophilia coexists with trauma, infection, inflammation, or surgery to give rise to a thrombotic process. Thrombosis may also arise from stasis, such as heart failure or cirrhosis. Hypercoagulable conditions include malignancies, heparin-induced thrombocytopenia, essential thrombocythemia, polycythemia vera, antiphospholipid antibodies, oral contraceptive use, and pregnancy. Heritable hypercoagulable conditions include sickle cell disease, Factor V Leiden, excess prothrombotic factors, and deficiencies in antithrombin III or proteins C or S.[3][4][5]

Patients with a thrombus in a major mesenteric vein often have concurrent portal vein thrombosis; such persons are more likely to have an underlying localized condition such as inflammatory bowel disease, pancreatitis, diverticulitis, myeloproliferative neoplasms, and malignancies. Portal vein involvement is also higher in persons with cirrhosis and has been reported in 15% of people awaiting liver transplantation. Patients with smaller vessel thrombosis in the vena rectae are more likely to have systemic thrombophilia.[6]

While up to 25% of cases of mesenteric vein thrombosis may initially be construed as idiopathic, thorough evaluation often reveals the causative etiology. For example, the gain-of-function JAK2V617F mutation results in a blood cell line proliferation; an assay for this mutation helps diagnose those with subclinical myeloproliferative disorders and can distinguish an inherited prothrombotic state from a reactive condition. The mutation is detected in most cases of polycythemia vera and 50% of cases of essential thrombocythemia and myelofibrosis. In addition, the JAK2V617F mutation is reported in up to 46% of cases without overt myeloproliferative neoplasms.[6][7][8]

Epidemiology

Acute mesenteric venous thrombosis causes 5% to 15% of all cases of mesenteric ischemia and accounts for 1 in 5,000 to 15,000 inpatient admissions and 1 in 1000 emergency department visits. The incidence of mesenteric venous thrombosis is estimated to be 2.7 per 100,000 persons. Computed tomography (CT) has increased the number of cases diagnosed during evaluation for other reasons, and this imaging modality identifies approximately 90% of mesenteric venous thromboses. Although mortality remains between 19% and 23%, there has been a trend toward earlier diagnosis and improved outcomes. Mesenteric venous thrombosis is slightly more common in men and most frequently presents in persons between the ages of 40 and 60.[9][3]

Pathophysiology

The superior mesenteric vein returns blood from the bowel from the second portion of the duodenum to the proximal two-thirds of the transverse colon, joining the splenic vein posterior to the neck of the pancreas, forming the portal vein. The left gastric vein drains the lower part of the esophagus and a portion of the lesser curvature of the stomach and enters the portal system at the formation of the portal vein. The inferior mesenteric vein drains the left colon and enters the splenic vein.

The pathophysiology of mesenteric venous thrombosis depends on the acuity, location, and causative etiology of the thrombus. Systemic thrombophilia causes thrombi within the vena rec. In contrast, local factors, such as intraabdominal malignancy, pancreatitis, and diverticulitis, produce thrombi in the superior mesenteric vein, often with extension into the portal vein.

Thrombi within the small, more distal venous branches pose a risk for bowel infarction. Blood return from the bowel is impeded, resulting in venous engorgement and subsequent ischemia. Arterial spasms can also contribute to irreversible ischemia. The bowel mucosa becomes permeable at sites of infarction, permitting the translocation of bacteria and leading to sepsis.[3][4] 

In chronic mesenteric venous thrombosis, collateral circulation develops in the form of extensive cavernoma around the chronically thrombosed area. Often, portal hypertension, varices, and thrombocytopenia coexist with chronic venous thrombosis, and those with portal venous thrombosis have splenomegaly secondary to tissue fibrosis. If the thrombosis is distal to the junction of the left gastric and portal vein, both esophageal and gastric varices are seen. However, if the thrombosis is proximal to this point, gastric varices predominate.[10][11]

Patients with chronic mesenteric venous thrombosis are at risk for many impairments of the gastrointestinal system. Significant bowel edema arises in the setting of extensive chronic thrombosis within the portal, superior mesenteric, and splenic veins. Over time, a patient with considerable chronic thrombosis may develop clinically significant small bowel and biliary strictures that can cause malnutrition and cholangitis.[12]

History and Physical

The history and physical of a patient with mesenteric venous thrombosis will vary depending on the acuity and etiology of the thrombosis. The presentation can range from an asymptomatic patient whose thrombosis is an incidental finding to an acutely ill patient with peritonitis and sepsis. Often, a patient with mesenteric venous thrombosis will describe several days of diffuse abdominal pain with anorexia, nausea, and vomiting. The history may involve an antecedent infectious or inflammatory condition. Patients may have a personal or family history of thrombosis; this should raise the suspicion of a hereditary coagulopathy. A patient with a chronic mesenteric venous thrombosis may have any underlying condition of greater concern, such as portal hypertension.[3][13]

In a patient with chronic mesenteric venous thrombosis, the physical examination may be unremarkable, or there may be stigmata of portal hypertension and cirrhosis such as spider nevi, palmar erythema, caput medusae, or evidence of esophageal variceal bleeding. Abdominal distension, discomfort, and ascites may be present.[14]

Patients with acute mesenteric venous thrombi often experience pain out of proportion to physical findings, along with nausea, vomiting, and diarrhea. Fever may indicate a concurrent infection, such as phlebitis, or an intraabdominal process, such as appendicitis or diverticulitis. A patient may exhibit dehydration and hemodynamic instability. 

Patients with subacute mesenteric venous thrombosis experience symptoms over days to weeks; the average duration of symptoms varies from 6 to 14 days. In patients with a subacute thrombotic process, abdominal distension may be present, and pain is often mild-to-moderate and diffuse. Ascites may be evident.[12]

Evaluation

Imaging Studies

Abdominal imaging is the most useful diagnostic tool to evaluate mesenteric venous thrombosis. An abdominopelvic CT with intravenous contrast can diagnose mesenteric venous thrombosis in 90% of cases. Plain abdominal radiographs reveal abnormalities in 50% to 75% of cases but demonstrate nonspecific findings such as dilated bowel, thumbprinting, and, in cases of perforation, free air. Magnetic resonance imaging (MRI), angiography, and abdominal Doppler ultrasonography are less commonly employed imaging modalities when evaluating patients with suspected mesenteric venous thrombosis. Abdominal Doppler ultrasonography can detect thrombosis in larger veins but has only 73% to 80% sensitivity and cannot visualize smaller vena recta.[15][16]

A venous thrombus will be seen as a focal lucency on CT images. Radiographic signs of ischemia include bowel wall thickening greater than 3mm with thickened mesentery and surrounding fluid. In the setting of a transmural bowel infarction, the bowel wall may be greater than 10 mm thick. The presence of portal venous gas and pneumatosis suggest necrotic bowel. Intraabdominal free air indicates bowel perforation.[17] 

When a mesenteric venous thrombosis is identified on CT, magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) permits further assessment of the biliary system and degree of portal hypertension; ERCP carries a risk of bleeding from catheter injury. Esophagogastroduodenoscopy (EGD) is recommended to evaluate for esophageal and gastric varices.[18] 

Laboratory Testing

Routine laboratory testing is not specific for mesenteric venous thrombosis but provides general clinical information. Recommended laboratory studies include a complete blood count with a differential, comprehensive metabolic panel, coagulation tests, and a thrombophilia screen. An elevated lactate level is a late marker of ischemia, and amylase levels can also be elevated with bowel ischemia; amylase levels greater than 1000 U/L suggest pancreatitis. Blood cultures should be obtained from patients with fevers and hemodynamic instability. Patients with portal vein involvement or sepsis will have elevated liver enzymes.[3][19][20]

Treatment / Management

Treatment for acute and subacute mesenteric venous thromboses can range from bowel rest, resuscitation, and anticoagulation to extensive surgery with bowel resection. Treatment goals are to prevent bowel infarction, mitigate blot extension, and minimize recurrence risk. Initial treatment depends on clinical presentation, the acuity of the thrombosis, and the underlying etiology. Stable patients may be treated nonoperatively with bowel rest, electrolyte replacement, and anticoagulation. Nasogastric decompression is often necessary, and total parenteral nutrition may be indicated. Febrile patients may benefit from broad-spectrum antibiotics to treat thrombophlebitis or enteric bacterial translocation.[21] 

Significant clot burden and clinical deterioration warrant invasive intervention. Historically, the only option for urgent intervention was open surgery. Interventional radiology (IR) can offer precise therapy such as catheter-directed thrombolysis, thrombectomy, and focal administration of pharmacologic agents, including papaverine for vasodilation, or tissue-type plasminogen activator (tPA) or streptokinase for clot lysis. These IR measures often result in symptomatic improvement and lower bowel resection rates, even with persistent radiographic thrombus.[3]

During an IR procedure, access is obtained percutaneously via a transjugular or transhepatic approach.[22][23] A 4F or 5F angiographic catheter over a 0.035-inch hydrophilic guidewire is used to cross the thrombus. The angiographic catheter is exchanged with a multi-sidehole perfusion catheter, and the tip is placed in the mesenteric vein. If using tPA, an initial dose of 5 mg is given, followed by continuous tPA infusion at 0.5 mg/h. Heparin sodium 40 mg every 12 hours and 80,0000 U/day of urokinase can also be used. A post-procedural venogram is performed. Contraindications for catheter-directed fibrinolysis include intracranial hemorrhage, a history of stroke, primary or metastatic central nervous system disease, recent surgery, trauma, and mesenteric infarction.[21][22][23]

Open surgery is indicated if a patient becomes septic from ischemic bowel or a perforated viscus. The area of thrombosis is identified, and the affected bowel segment is resected. The goal of surgery is bowel conservation while resecting necrotic segments, and the average length of resection is 50 to 60 cm. Intraoperative Doppler ultrasonography may be used to assess the mesenteric blood supply. The surgeon may return in 24 hours for a second look before completing the anastomosis if there are concerns for ongoing ischemia.[2][20][24][25](B2)

Anticoagulation is the cornerstone of mesenteric venous thrombosis treatment. While there remains a possibility of invasive intervention, or for patients with renal insufficiency, the initial anticoagulant of choice is unfractionated heparin. Once the patient is stable, the anticoagulant is changed to an oral medication such as warfarin or a direct oral anticoagulant (DOAC). Patients with reversible causes of thrombosis should complete a 6-month course of anticoagulation therapy, while those with heritable or acquired thrombotic states continue lifelong anticoagulation. 

Despite the risks, anticoagulation remains the mainstay of management, even in those patients with portal venous thrombosis who have cirrhosis and portal hypertension. Anticoagulation helps recanalize the vein. Patients with mesenteric venous thrombosis awaiting liver transplantation who receive anticoagulation experience recanalization in 50% of cases, while those not taking anticoagulation do not experience recanalization of the portal vein. Factors associated with failure of recanalization include splenic vein involvement, ascites, and significant clot burden.[3] 

Patients with portal hypertension may require intervention such as a transjugular intrahepatic portosystemic shunt (TIPS) to minimize bleeding risks before anticoagulation. The goal of a TIPS is mechanical recanalization of the portal vein to maintain flow across the occluded segment. In patients with cirrhosis, a shunt can be created between the left portal vein and the superior mesenteric vein, and splenectomy is effective in those patients with isolated gastric varices from splenic vein thrombosis. Stenting may be required for biliary strictures formed as a consequence of chronic portal vein thrombosis. Rarely a hepaticojejunostomy is required to overcome the stenotic bile ducts.[26][27]

Differential Diagnosis

The symptoms of mesenteric venous thrombosis can be vague and nonspecific and range from mild to severe. Physical examination and laboratory values alone generate a broad differential diagnosis, including a spectrum of intraabdominal pathology, myocardial infarction, and aortic dissection. It is also essential to distinguish mesenteric venous thrombosis from mesenteric arterial thrombosis, as the etiology and approach to treatment are different. Mesenteric venous thrombosis may exist concurrently with an inciting infectious or inflammatory process. 

Prognosis

While overall mortality has decreased due to earlier diagnosis and treatment, mesenteric venous thrombosis remains a life-threatening condition, and a delay in diagnosis directly correlates with worse outcomes. The most common causes of death in patients with mesenteric venous thrombosis are sepsis, pulmonary emboli, and the sequelae from recurrent thrombi. Patient age, comorbidities, time to diagnosis, and successful revascularization impact outcomes.[21]

Acute mesenteric venous thrombosis has a 30-day mortality of up to 32%. Timely diagnosis reduces mortality to less than 10%; the mortality rate approaches 60% when diagnosis is delayed.[28][21] If treatment is delayed longer than 24 hours from symptom onset, mortality ranges between 80% and 100%.[29] For patients with chronic mesenteric venous thrombosis, 5-year survival rates are up to 82%. In the paradigm of chronic thrombosis, the prognosis is determined by the severity of the underlying condition.[30] 

Complications

Complications of mesenteric venous thrombosis arise from the thrombosis, the treatments, and the underlying condition. Thrombosis recurrence usually occurs within the first 30 days and may be as low as 0% to 3% in those who receive anticoagulation. Recurrence or extension of thrombosis may give rise to bowel infarction, sepsis, and death. Short bowel syndrome may be a consequence of bowel resection, and some patients require lifelong total parenteral nutrition.[31]

Complications from catheter-directed thrombolysis include major and minor bleeding, fever, hematoma formation, pain, and infection. Transhepatic access for thrombolytic therapy carries an increased risk of bleeding, and the transileocolic approach may require surgical access. The bleeding risk from anticoagulation is less than 10%, and bleeding is usually within the gastrointestinal system. Patients with varices have a higher bleeding risk and should be pretreated with beta blockers or undergo definitive management of varices.[21][32] 

Chronic thrombosis can give rise to biliary strictures, gallstones, and recurrent cholangitis; major reconstructive surgery is required occasionally. The myeloproliferative neoplasms that predispose some patients to thrombosis can convert to leukemia and myelodysplasia. Patients with chronic thrombosis also suffer from chronic fatigue, bone pain, pruritis, weight loss, and bleeding from platelet dysfunction.[12]