Among the numerous causes of abdominal pain, vascular causes comprise an extremely important group that requires prompt recognition and detection. Although some of these abdominal events may be acute, others often present as a chronic debilitating disorder. Compromise of blood flow to and from the gastrointestinal tract may result in ischemia of varying degrees. Although most events are arterial in nature, 5% to 15% of cases involve the mesenteric venous structures. This vascular source of abdominal pathology often goes unrecognized and has a wide gamut of presentations. Most involve the superior mesenteric vein (SMV), but other processes involve the portal vein, splenic vein, hepatic vein, or inferior mesenteric vein (IMV). This chapter discusses the anatomy, etiology, pathophysiology, clinical presentation, diagnosis, and management of splanchnic venous disease. Furthermore, arteriovenous malformations (AVMS) of the gastrointestinal tract and certain rare vascular disorders are examined as related entities to splanchnic venous disease.

The venous anatomy parallels that of the splanchnic arterial system. The venous blood from most of the gastrointestinal tract drains into the liver via the portal venous system. The portal vein is formed by the confluence of the SMV and splenic vein. This vein is approximately 2 inches (5 cm) long and is formed behind the neck of the pancreas. The IMV joins the splenic vein before the portal venous confluence. The other tributaries of the portal vein include the left gastric vein, which drains the left portion of the lesser curvature of the stomach and distal esophagus. The right gastric vein also drains directly into the portal vein and drains from the right portion of the lesser gastric curvature. The cystic veins drain the gallbladder blood flow directly into either the portal vein or the liver.

The SMV is vital for drainage of blood flow from the small intestine, cecum, ascending colon, and transverse colon. It is formed by the jejunal, ileal, ileocolic, right colic, and middle colic veins. The pancreas and the duodenum receive venous drainage from the inferior pancreaticoduodenal vein. The IMV drains blood flow from the descending and sigmoid colon and the rectum. Specifically, the left colic vein and sigmoid branches flow into the IMV. The superior rectal vein drains blood flow from the rectum into the IMV.

In normal circumstances, the portal venous blood traverses the liver and drains directly into the inferior vena cava (IVC). However, in conditions that impede portal venous blood flow by this direct route, indirect communications become common between the portal and systemic circulations. These include the following communications. The left gastric vein portal tributary may form an anastomosis with the esophageal veins, which drain the middle third of the esophagus into the azygous vein. The paraumbilical veins connect the left branch of the portal vein with superficial systemic tributaries of the anterior abdominal wall. The superior rectal venous portal tributaries may communicate with the middle and inferior rectal veins, which subsequently drain into the internal iliac and internal pudendal veins, respectively. Venous drainage from the ascending and descending colon, duodenum, and pancreas may form portosystemic anastomoses with the renal, lumbar, and phrenic veins.

In addition to the portal vein and hepatic artery, the liver receives blood flow from the parabiliary venous system of Couinaud. This is a plexus of veins arising from the pancreatoduodenal or pyloric veins and drain directly into the portal vein or specific hepatic lobar segments.¹

During the fourth and fifth weeks of fetal development, the vitelline and umbilical veins are formed. The portal venous system arises from the two vitelline veins and the two umbilical veins. In the embryo, the yolk sac receives venous drainage from the vitelline veins, which communicate with the septum transversum. From the septum transversum, the liver sinusoids and lobules develop. The left vitelline vein gives rise to the extrahepatic portal venous system, and the umbilical veins are the origin of the intrahepatic circulatory system. In the fetal circulation, a vast amount of blood bypasses the liver because of the direct communication of the left umbilical vein to the IVC. Soon after birth, the left umbilical vein is obliterated and results in the normal adult portal venous circulation. The left umbilical vein develops an anastomosis with the hepatic sinusoids, creating a shunt of blood into the IVC through the ductus venosus. The ductus venosus closes after birth to become the ligamentum venosum.

Surrounding the duodenum, a plexus of vessels is formed by the vitelline veins before entering the sinus venosus. Liver cords then interrupt the course of these vessels, resulting in an extensive network of vasculature known as hepatic sinusoids. There is initiation of left-to-right shunts between the vitelline veins. The proximal portion of the left vitelline vein disappears closer to the second or third gestational month. The network of vessels surrounding the duodenum develops into a single vessel, the portal vein. Despite the complexity of development of this area, congenital abnormalities of the portovenous circulatory system are rare.^2,3

Cause

Splanchnic venous disease usually involves thrombosis of the mesenteric veins, most commonly the SMV. This can be present as a primary mesenteric venous thrombosis or a secondary acquired condition. A cause can usually be found in approximately 75% of cases, with the most common sources being either a primary hereditary coagulation disorder or a secondary thrombosis from cancer, intraabdominal inflammation, or cirrhosis (Table 27-1).

Primary Mesenteric Vein Thrombosis. The most common source of primary thrombosis of the mesenteric veins is the group of hereditary hypercoagulable disorders. Deficiency of proteins C and S, antithrombin III, and factor V Leiden have been implicated in primary mesenteric venous thrombosis.

Inherited protein C deficiency occurs as a result of one of more than 160 mutations of protein C gene on chromosome 2. Acquired deficiency has been reported in relation to warfarin use, septic shock, liver disease, and chemotherapeutic agents. Clinical manifestations most commonly include deep venous thrombosis of the extremities and sometimes pulmonary embolism. Mesenteric venous thrombosis is rare but is a characteristic feature of this disorder. It results in abdominal pain out of proportion to physical findings, and in severe cases, it may include vomiting, abdominal distension, melena, or hemorrhagic bowel infarction.^4,5

Protein S deficiency can be hereditary with an autosomal dominant trait or an acquired condition that is most commonly caused by hepatic disease or vitamin K deficiency. Mesenteric arterial thrombosis is not reported with this condition, and mesenteric venous thrombosis is also rare but more frequent in the inherited rather than acquired type of protein S deficiency.^6,7

Similarly, antithrombin III deficiency may occur as a hereditary disorder or an acquired condition. The latter may be precipitated by pregnancy, liver disease, acute respiratory distress syndrome, nephrotic syndrome, bone marrow transplantation, or oral contraceptives.

Factor V Leiden thrombophilia is a fairly common inherited disorder that has no clinical manifestations in most cases. However, similar to the other inherited disorders of anticoagulation thus far described, factor V Leiden thrombophilia also results in venous thrombosis and an increased risk of spontaneous abortions. Its potential clotting complications can be worsened by oral contraceptives and estrogen hormone replacement therapy. Heparin followed by warfarin is required for long-term anticoagulation and prevention of complications.⁸

Antiphospholipid syndrome is characterized by hypercoagulability, complications of pregnancy (e.g., spontaneous abortions, unexplained fetal death, premature birth), and the presence of cardiolipin or lupus anticoagulant antibodies. The production of such antibodies may be elicited by exposure to certain medications, including certain antibiotics, cocaine, procainamide, hydralazine, and quinine. This disorder may result in either arterial or venous thrombosis. Additionally, it is often characterized by thrombocytopenia, mottling discoloration of the skin (livedo reticularis), migraine headaches, and transverse myelitis. More than 50% of patients with systemic lupus erythematosus have detectable antiphospholipid antibodies. Although the cause of thrombosis is not completely understood, it has been demonstrated that antiphospholipid antibodies result in reduced levels of the annexin V, which is a protein that binds phospholipid and has potent anticoagulant activity.⁹ Treatment of patients with this disorder includes anticoagulation with heparin-related agents, warfarin, or antiplatelet agents such as aspirin. Some patients respond to prednisone, hydroxychloroquine (in the setting of lupus), or intravenous immunoglobulin therapy.¹⁰

Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely uncommon condition characterized by the triad of hemolytic anemia; pancytopenia (often aplastic anemia); and thrombosis of large vessels such as those of hepatic, mesenteric, subdermal, or cerebral locations. Venous thrombosis in this condition can be catastrophic and is usually characterized by severe abdominal pain, acute ascites formation, and rapidly developing hepatomegaly caused by hepatic vein obstruction (Budd-Chiari syndrome). Thrombosis of the abdominal veins is usually manifested by upper abdominal pain lasting 1 to 6 days and has been reported to result in acute bowel infarction in severe states.^11,12

Secondary Mesenteric Vein Thrombosis. Paraneoplastic disease results in an acquired or secondary form of hypercoagulability. This is particularly noted in intraabdominal malignancies such as lymphoma, mostly after chemotherapy. Direct injury to endothelial cells along with reduced blood flow has been demonstrated to be the mechanism of this condition.¹³ Other tumors in advanced stages, such as hepatocellular carcinoma, hilar cholangiocarcinoma, metastatic colon cancer, and pancreatic adenocarcinoma, have been associated with thrombosis of SMV, hepatic veins, and portal veins. Often, surgical resection of these tumors requires thrombectomy or vascular reconstruction.¹⁴ Thrombosis of the IVC often occurs in patients with hepatic malignancy and may preclude successful surgical resection.¹⁵

Pancreatitis commonly results in peripancreatic vascular disease. SMV thrombosis has been shown to occur as a result of pancreatic inflammation by itself as well as in the background of hypercoagulable disorders such as protein C deficiency.¹⁶ Although the pancreatitis may result in SMV thrombosis, the most common vascular complication is splenic vein thrombosis (see below).

Inflammatory bowel disease may result in secondary vascular thrombosis. In both Crohn’s disease and ulcerative colitis, it has been shown that increased platelet activation and platelet-leukocyte aggregation occur within the mesenteric veins.¹⁷ Acute bowel inflammation triggers a secondary thrombotic process in these individuals. Furthermore, multiple studies have shown that mesenteric venous occlusion may occur in the postoperative state after colectomy for inflammatory bowel disease.^18,19

Cirrhosis and portal hypertension may result in increased thrombosis of the portal vein and splanchnic vasculature. In most settings of cirrhosis, bleeding and reduced blood clotting are noted. However, portal vein thrombosis is noted in 10% to 20% of all patients with cirrhosis. Furthermore, portal hypertensive states may be associated with SMV thrombosis. Venous stasis in the portal vein is the major contributor to thrombogenesis in the splanchnic vessels even without other factors such as hypercoagulable disease. Platelet function and number may also contribute to this development.^20,21 Splanchnic arterial vasodilation occurs in the setting of elevated portal pressures and subsequently results in reduced venous dynamic flow. Furthermore, hepatic nitric oxide synthesis is found to be reduced in chronic liver disease and contributes to the reduced dynamic blood flow in the splanchnic vessels.²² Thus, many therapies for portal hypertension are aimed at splanchnic vasoconstriction with agents such as β-blockers, vasopressin derivatives, and somatostatin (see information on portal vein thrombosis below).

Previous sclerotherapy of varices has been demonstrated to result in perivascular inflammation and scarring. In some cases, this has been shown to subsequently result in portal and mesenteric venous thrombosis.²³ Such findings are much less common today because band ligation has replaced most cases of sclerotherapy for the treatment of esophageal varices. Sclerotherapy is still used in endoscopic treatment of active variceal bleeding in which blood obscures the site of bleeding, including the varices themselves.

Splenectomy has been a long recognized cause of development of portal and mesenteric venous thrombosis. The incidence of this has been described to be 5% of all patients, with the highest risk being those who had prior splenomegaly, thrombocytosis, or congenital thrombophilia disorders.²⁴ Splanchnic vascular thrombosis has been demonstrated to occur with a much higher frequency after laparoscopic rather than open splenic resection.²⁵

Postoperative states have been described above for colectomy and splenectomy as sources of perivascular inflammation and subsequent vascular thrombosis. Such a process has been described to occur in cases of gastrectomy, pancreatectomy, hepatic surgery, adrenalectomy, laparoscopic cholecystectomy, and small intestinal resection.

Blunt trauma to the abdomen has been long known to result in vascular injury. Mesenteric ischemia has been shown to occur from venous thrombosis and low-flow states. Furthermore, trauma may result in bowel wall injury with secondary venous congestion and stasis and subsequent ischemia. Supportive care to improve blood flow is needed along with abdominal surgical repair, which may include thrombectomy or vascular bypass.^26,27

An important but often ignored source of secondary venous thrombosis is the use of oral contraceptives. This accounts for approximately 9% to 18% of cases of secondary thrombosis, particularly in young women.²⁸ The Janus kinase 2 V617F mutation is an acquired mutation found in patients with myeloproliferative disorders and has been found to have a high incidence in cases of portal or SMV thrombosis. In recent studies, this mutation has been identified as a risk for thrombogenesis in young women who use oral contraceptives.²⁹

Pathophysiology

Ischemia from mesenteric venous thrombosis results from a different pathophysiologic process than that from arterial ischemia. The latter results from direct interruption of blood flow to the intestine and subsequent cellular injury with necrosis. Mesenteric arterial blood flow may carry 25% to 40% of cardiac output at a given time, and mesenteric venous blood flow may carry 30%. Venous thrombosis results in massive influx of fluid into the bowel lumen with subsequent bowel wall edema. This results in venous outflow impairment and more importantly impedes arterial blood flow into the bowel. The mucosa and submucosa of the intestine use 70% of the arterial blood flow and are highly sensitive to such impairment. After ischemia occurs, the resolution to normal bowel is gradual, unlike that of arterial ischemia, which resolves quickly when normal bowel blood flow resumes.

The manifestations of mesenteric venous thrombosis are attributable to the extent of thrombus, the size of the involved vessels, and the depth of bowel wall ischemia. Intraabdominal causes such as inflammatory processes initially affect larger vessels with thrombosis and then lead eventually to involvement of smaller venous arcades and arcuate channels. In contrast, prothrombotic vascular disorders start from smaller vessels and progress to larger vessels.

The portal vein does not contain valves, so pressure within it can be freely transmitted back to afferent branches. Normal portal venous pressure ranges from 5 to 10 mm Hg. Two-thirds of the hepatic blood flow (~1 L/min) is supplied by the portal vein; the remainder is supplied by the hepatic artery, thus creating a dual blood supply. Thus, ligation of the portal vein alone will not result in hepatic necrosis. It is estimated that 80% of the hepatic sinusoidal flow would have to be obliterated to result in an increase of the portal venous pressure.³⁰ Moreover, compensatory regulation between arterial and venous inflow into the liver exists with one being reduced while the other is increased.³¹

Clinical Characteristics of Superior Mesenteric Vein Thrombosis

Primary or secondary thrombosis of the SMV accounts for 95% of cases and 5% to 15% of all intestinal ischemic events. Thrombosis may result in either acute or subacute or chronic disease. Acute mesenteric venous ischemia accounts for 5% to 10% of all acute mesenteric ischemia. It has a fairly even distribution between males and females and affects individuals with an average age of 48 to 60 years.³² Abdominal pain is the fundamental symptom in all presentations, and in the acute mesenteric venous ischemic setting, pain is often out of proportion to the physical examination findings. In chronic or subacute states, symptoms may be vague or absent. Sometimes venous thrombosis is incidentally found during abdominal radiographic imaging such as computed tomography (CT).

In most cases, abdominal pain often starts as a vague discomfort and progresses insidiously over 7 to 10 days into severe abdominal pain. On physical examination, abdominal tenderness with guarding may be noted in those with acute ischemia. The presence of rebound tenderness and abdominal distension suggests peritoneal irritation and likely full-thickness bowel infarction. Nausea, vomiting, or bowel evacuation may also accompany abdominal pain but are nonspecific and not reliable features for diagnostic purposes. Patients with postprandial abdominal pain may be mistaken for having other conditions such as peptic ulcer disease or biliary colic. Those with diarrhea and abdominal pain may have a similar presentation to intestinal infections or Crohn’s disease.

Hemodynamic instability with collapse and shock are late findings that signal a poor outcome. Invariably, acute mesenteric venous thrombosis with bowel infarction is fatal unless intervention occurs. The most worrisome feature of acute SMV thrombosis is bowel infarction and subsequent necrosis. In a series of 27 cases of acute venous thrombosis, 22 (81%) required operative management with bowel resection. However, a high mortality rate of eight patients (29.6%) suggests that this can be a catastrophic event despite surgical intervention.³³

Acute mesenteric ischemia may develop within the course of minutes to hours after thrombosis of a major splanchnic vein. Although this is a rare occurrence, the presentation may be catastrophic and requires prompt recognition. Ascites may develop in acute mesenteric venous thrombosis, and paracentesis reveals bloody fluid, especially in complete bowel infarction. The presence of ascites and abdominal pain in a patient who has a personal or family history of thrombotic disease should prompt evaluation for mesenteric venous thrombotic disease.

In chronic forms of mesenteric venous thrombosis, vague abdominal pain that is worse during digestion or postprandial states may be noted. Furthermore, complications of portal vein thrombosis may include bleeding from esophageal varices. Chronic thrombosis of the splenic vein (SVT) such as results from intraabdominal inflammation, including pancreatitis, may result in isolated gastric varices formation with esophageal varices. Hematemesis, hematochezia, or melena is reported to occur in 15% of acute, subacute, and chronic mesenteric venous thrombosis.³⁴ However, occult blood in the stool is detectable in nearly 50% of patients.³⁵

Diagnostic Tests

The recognition of this clinical entity is often challenging because the presentation can be insidious with rapid progression in some cases into an acute bowel ischemia. Laboratory tests are usually not helpful and are nonspecific. Among routine blood tests, the presence of lactic acidosis and leukocytosis may suggest acute bowel ischemia but unfortunately are late findings. Other laboratory parameters, such as prothrombin time, activated partial thromboplastin time, and chemistry profile, should be checked. After venous thrombosis has been confirmed, the source can be evaluated for hypercoagulable disorders with protein C, protein S, antithrombin III deficiency, or lupus anticoagulant. In patients with a suspected myeloproliferative disorder, bone marrow examination may be necessary.

Plain abdominal film results are normal in more than half of patients with mesenteric venous thrombosis. However, specific findings may be seen in about 5% of individuals. These include thumbprinting or blunt, partially opaque indentations of the bowel lumen, resulting from mucosal edema. This finding along with gas within the intestinal wall (pneumatosis intestinalis) or portal venous gas suggests bowel infarction from mesenteric venous thrombosis. Free peritoneal air may be noted in advanced states of infarction and micro- or macroperforation. In the performance of these radiographic studies, barium should be avoided in the setting of acute mesenteric venous thrombosis.³⁶

CT of the abdomen has been shown to be as accurate as arteriography in the diagnosis of mesenteric venous occlusion and perhaps provides more information. CT may show an enlarged portal vein or SMV with surrounding edema and sharp delineation of the venous wall. Sometimes a thrombus can be visualized within the vein. Although CT imaging will identify mesenteric venous thrombosis in 90% of cases, it may not be as accurate in early thromboses of small mesenteric vessels.^37,38 Arteriography tends to show vasospasm, a lack of venous contrast flow, contrast within the bowel lumen, reflux of contrast into the aorta, and absent flow to areas of bowel necrosis. Magnetic resonance imaging (MRI) is also very sensitive, but because of time and cost, CT of the abdomen with contrast and delayed phase imaging is perhaps more effective. Duplex sonography may be helpful in early stages of ischemia with color-flow imaging and may reveal thrombus in the mesenteric veins. However, it is less accurate then CT imaging, particularly when limited by time, bowel gas interference, and patient discomfort (Figure 27-1).

Endoscopy and colonoscopy are of limited value given the rarity of colonic and duodenal involvement by mesenteric vein thrombosis. Endoscopic ultrasound imaging with color-flow Doppler may help detect mesenteric vascular thrombosis. However, this is more useful in chronic thrombotic disease because bowel distension may not be safe or comfortable to the patient in acute thrombosis. After acute inflammation subsides, endoscopic or barium studies may be useful to investigate the possibility of inflammatory bowel disease.

Abdominal CT should therefore be performed early in the course of disease when suspicion is present for mesenteric venous thrombosis. This helps to define not only the thrombosis but also the extent of bowel involvement. Mesenteric angiography should be reserved for those in whom small vessel thrombosis is suspected in the background of thrombophilic history but in whom CT imaging results are negative.

Acute thrombosis of the mesenteric venous system requires urgent management to avoid catastrophic complications, particularly vascular congestion and subsequent bowel ischemia. Chronic thrombosis also requires therapy in symptomatic patients.

Medical Therapy

Fortunately, mesenteric venous thrombosis has much less of an ominous prognosis than mesenteric arterial thrombosis. It has been shown that acute venous thrombosis has an 88% rate survival at 24 month follow-up.³⁹ Observation may be sufficient with or without anticoagulation in patients who are asymptomatic and in those with incidentally found disease. Anticoagulation with heparin or warfarin has been used in patients with acute thrombosis who have not progressed to bowel infarction or perforation, especially in the setting of acquired hypercoagulable disorders. However, despite systemic anticoagulation, acute mesenteric venous occlusion has been shown to progress to intestinal ischemia and infarction in 18% of cases.⁴⁰ Thus, more definitive or thrombus-directed therapy may be required. Gastrointestinal bleeding and shock may also be complications and carry a mortality rate of approximately 50% in acute venous thrombosis. Systemic anticoagulation should be orally administered for a minimum of 3 to 6 months and may be required lifelong for individuals in whom a hypercoagulable disorder is detected or in whom chronic mesenteric vein thrombosis develops. Other medical therapy has included papaverine, an opium alkaloid, with vasodilator properties in both acute venous and arterial mesenteric thrombosis as reported in a few small series.⁴¹

Percutaneous Vascular Interventions

In recent years, percutaneous access to the mesenteric venous system with selective endovascular delivery of thrombolytic agents has been shown to have high success rates. Direct administration is performed by transhepatic or transjugular–transhepatic routes but is technically difficult. Moreover, it is associated with a high bleeding risk. The intraarterial or indirect route of administration of thrombolytics to the mesenteric venous thrombus can be achieved by route of the small mesenteric artery. This is a simpler approach with fewer bleeding complications than the direct approach and permits breaking up clots within capillaries and venules. The most common agents are urokinase, streptokinase, and tissue plasminogen activator (tPA).⁴² Administration of this therapy within a few hours of onset of acute venous thrombosis leads to the best outcome. Caution should be taken in patients who are at risk for intracranial or gastrointestinal bleeding from other sources. After endovascular thrombolytic therapy, most patients are placed on long-term systemic oral anticoagulants.⁴³ Larger series of studies are required to determine the long-term outcomes and safety of thrombolytic use in this setting.

Operative Management

Severe complications of acute mesenteric venous occlusion, albeit rare, are important to recognize and treat in an expedient manner. Peritoneal signs on examination, transmural bowel ischemia or infarction, and intestinal perforation are clear indications for surgical exploration and management. Minimally invasive surgical options include venous thrombectomy, but this may be technically challenging.

The left-sided version of portal hypertension involves SVT. SVT is an important entity because it may result in massive gastrointestinal bleeding from the subsequent formation of esophageal or gastric varices. In certain cases, isolated SVT is noted and is a unique entity most often related to pancreatic disease. Perivenous inflammation of the splenic vein may result in SVT in the setting of acute or chronic pancreatitis or even pancreatic carcinoma. Intrinsic endothelial damage from pancreatic inflammation or neoplasia may be part of the pathogenesis. Furthermore, extrinsic vascular damage occurs from venous compression caused by fibrosis, adjacent pseudocysts, or edema. Enlarged retroperitoneal lymph nodes, peripancreatic lymphadenopathy, and perisplenic lymph nodes may also cause extrinsic obstruction of the splenic vein.^44,45

SVT results in the formation of collateral vessels to shunt blood flow around the occluded vessels. The short gastric veins develop increased blood pressure because they provide a communication between the portosystemic collateral vessels and the azygous venous system in the distal esophagus. In the stomach, the splenoportal collateral vessels use the short gastric vessels to communicate with the portal vein and SMV. The hypertensive short gastric veins cause increased pressure in the submucosal gastric veins and subsequently form gastric varices.⁴⁶