INTRODUCTION — The portal vein is formed by the confluence of the splenic and superior mesenteric veins, which drain the spleen and small intestine, respectively (figure 1). Portal hypertension develops as a result of obstruction to flow within the portal venous system. It can be categorized as prehepatic, intrahepatic, or posthepatic based upon the site of obstruction to flow (table 1). The intrahepatic causes of portal hypertension have been further subdivided as presinusoidal, sinusoidal, or postsinusoidal based on the location of the obstruction to portal blood flow within the liver. Causes of extrahepatic portal vein obstruction include thrombosis and invasion or constriction by a malignant tumor.
This topic will review portal vein thrombosis (PVT), the most common cause of extrahepatic portal vein obstruction. Other important causes of noncirrhotic portal hypertension (including noncirrhotic portal fibrosis and schistosomiasis) and the clinical manifestations, diagnosis, and treatment of acute and chronic PVT are discussed separately. (See "Noncirrhotic portal hypertension" and "Acute portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management" and "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management".)
EPIDEMIOLOGY — The incidence of PVT among patients without cirrhosis is unclear. It is thought to account for 5 to 10 percent of patients with portal hypertension in developed countries and up to one-third of patients in resource-limited countries (because of an increased frequency of infectious complications that predispose to PVT) [1,2]. Among patients with cirrhosis, PVT is common and is associated with the severity of the patient's liver disease [3,4]. Autopsy studies have reported prevalences of 6 to 64 percent, whereas studies that used ultrasonography to diagnose PVT reported prevalences of 5 to 24 percent [5]. The prevalence of PVT is estimated to be less than 1 percent in patients with compensated cirrhosis, but is 8 to 25 percent in patients who are candidates for liver transplantation [6,7].
In a study of almost 24,000 autopsies in Sweden performed between 1970 and 1982, the prevalence of PVT was 1 percent [8]. The most common predisposing conditions for PVT were cirrhosis (28 percent), primary or secondary hepatobiliary malignancy (23 and 44 percent, respectively), major infectious or inflammatory abdominal disease (10 percent), or a myeloproliferative disorder (3 percent). However, no predisposing factors were identified in 14 percent.
PATHOGENESIS — Portal vein thrombosis (PVT) in patients with a previously healthy liver is thought to be due to inherited or acquired prothrombotic states [9] (table 2). However, no apparent cause for PVT is identified in more than 25 percent of patients [10-12]. Among patients with cirrhosis, the pathogenesis is likely related to unbalanced hemostasis and slowing of portal flow [13]. (See "Overview of the causes of venous thrombosis" and "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors".)
Inherited conditions associated with PVT include [3,14-20]:
●Factor V Leiden
●Prothrombin gene mutation
●Protein C deficiency
●Protein S deficiency
●Antithrombin deficiency
●Increased factor VIII levels
The relative frequency of prothrombotic disorders in patients with PVT is illustrated by observations from two series:
●In a case-control study of patients with cirrhosis, prothrombotic states were more common in the 23 patients with PVT than in the 40 patients without PVT, including mutations in factor V Leiden (13 versus 7.5 percent), the prothrombin gene (35 versus 2.5 percent), and the MTHFR gene (44 versus 5 percent) [14]. Overall, a thrombophilic genotype was detected in 70 percent of patients.
●The second study compared 65 patients with PVT without overt neoplastic disease or cirrhosis with 500 patients with lower limb deep vein thrombosis (DVT) and 700 healthy controls [18]. At least one thrombophilic abnormality was detected in 40 percent of patients with PVT or DVT, compared with only 13 percent of controls. PVT was associated with the prothrombin gene mutation and deficiencies of antithrombin, protein C, and protein S. Prothrombin gene mutations were more likely in those with PVT than in those with DVT. (See "Prothrombin G20210A".)
Acquired conditions associated with PVT include [15,18,21-28]:
●Cirrhosis
●Hepatocellular carcinoma
●Philadelphia-chromosome negative chronic myeloproliferative disorders (polycythemia vera, essential thrombocythemia, idiopathic myelofibrosis, unclassifiable myeloproliferative disorders) (see "Overview of the myeloproliferative neoplasms")
●Antiphospholipid syndrome
●Paroxysmal nocturnal hemoglobinuria
●Behçet syndrome
●Recent pregnancy or oral contraceptive use
●Abdominal inflammatory lesions including infection, pancreatitis, and inflammatory bowel disease
●Trauma
Procedures that have been associated with PVT include [15,23,26,29-32]:
●Abdominal surgery or surgical injury of the portal vein axis
●Endoscopic sclerotherapy
●Transjugular intrahepatic portosystemic shunt
●Splenectomy
●Hepatic resection
●Pancreatic islet cell transplantation
Patients often have multiple risk factors for PVT, so in general, PVT should not be attributed to a single etiology without first evaluating for other predisposing conditions [15,18,21]. In a study of 92 patients with portal vein thrombosis, zero, one, two, three, or four simultaneous acquired or inherited risk factors were seen in 16, 47, 24, 10, and 3 percent of patients, respectively [15]. Among patients with cirrhosis, patients with PVT are more likely than patients without PVT to have mutations associated with prothrombotic states (factor V Leiden, MTHFR, and prothrombin gene mutations) [3,14,33].
COMPLICATIONS — Portal vein thrombosis can lead to complications such as intestinal ischemia, portal hypertension, and portal cholangiopathy.
Intestinal ischemia — Extensive thrombosis involving the mesenteric venous arches may lead to intestinal ischemia and eventually infarction [34,35]. This is typically seen in acute PVT because collaterals have not yet developed. The ischemia is likely related to obstruction of mesenteric venous outflow and reflex arterial constriction and occlusion. (See "Mesenteric venous thrombosis in adults" and "Acute portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management", section on 'Prognosis'.)
Septic portal vein thrombosis — Septic portal vein thrombosis (acute pylephlebitis) occurs when PVT develops in a patient with an abdominal focus of infection, though the source of the infection may be difficult to find. Typically, the infection is with Bacteroides fragilis or Escherichia coli, though other pathogens have also been found. (See "Pylephlebitis", section on 'Pathogenesis' and "Pylephlebitis", section on 'Microbiology'.)
Portal hypertension — Portal hypertension is responsible for the majority of the complications seen in patients with chronic PVT. It also leads to the formation of collaterals around the obstructed portal vein, known as a cavernous transformation of the portal vein or portal cavernoma.
Portal hemodynamics — Portal venous pressure is determined by the product of portal venous flow and the resistance to outflow from the portal venous system:
●Portal pressure = portal venous flow x portal venous outflow resistance
Portal hypertension is defined by a hepatic venous pressure gradient (HVPG) greater than 5 mmHg. It is usually caused by an increase in resistance in the portal-hepatic vascular bed due to obstruction to flow. In patients with PVT, it occurs because of obstruction to flow in the portal vein. (See "Cirrhosis in adults: Overview of complications, general management, and prognosis", section on 'Complications of portal hypertension'.)
Differences in portal hemodynamics in the settings of acute and chronic portal vein occlusion have been studied in animal models. One model involved acutely clamping the portal vein [36]. This produced a reflex increase in splanchnic arteriolar tone that decreased flow into the portal vein and tended to nullify the effects of increased portal venous resistance from the clamp [36]. On the other hand, in an animal model of chronic portal vein stenosis, there was a paradoxical decrease in splanchnic arteriolar tone leading to increased portal flow, which compounded and perpetuated the portal hypertensive state and contributed to the hyperdynamic circulation associated with portal hypertension [37].
The hyperdynamic circulation in the portal vein stenosis model was less prominent than that seen in cirrhosis, a setting in which increased production of nitric oxide also contributes [38]. The reasons for this difference are not well understood. While it has been hypothesized that impaired hepatic reticuloendothelial function allows bacteria and endotoxins to reach the systemic circulation and activate nitric oxide production, experimental models do not support a role of endotoxin in prehepatic portal hypertension [39]. Rather than an endotoxin-induced increase in iNOS (the inducible form of NO synthetase), it is the constitutively expressed NO synthetase (eNOS) that is increased [38,40,41].
Varices — Patients with PVT frequently form varices [42]. When only a segment of the portal venous bed is obstructed, varices develop only in areas that decompress the corresponding segment. As an example, segmental portal hypertension within the splenic vein (splenic vein thrombosis) is associated with the formation of isolated gastric varices in the fundus of the stomach (picture 1). On the other hand, patients with portal vein thrombosis commonly form varices in sites other than the esophagus and stomach (ectopic varices) [43].
Ascites — Sinusoidal portal hypertension (portal pressure >12 mmHg) is usually required for the formation of ascites. Thus, patients with isolated presinusoidal or prehepatic portal hypertension (as is seen with PVT) typically do not have significant ascites unless they develop acute dilutional hypoalbuminemia during fluid resuscitation for a variceal bleed or have associated cirrhosis. By contrast, ascites more readily forms in postsinusoidal and posthepatic portal hypertension (eg, from Budd-Chiari syndrome), even in the absence of well-established cirrhosis. (See "Pathogenesis of ascites in patients with cirrhosis".)
Portal cholangiopathy — Portal cholangiopathy (also referred to as portal biliopathy) is a complication that may be seen in patients with longstanding PVT. Portal cholangiopathy develops when the venous collaterals that form in the setting of portal hypertension compress and deform the large bile ducts [44,45]. It has been hypothesized that this may lead to stricture formation, fibrous scarring of the porta hepatis, and ischemic injury to the bile ducts resulting in stricture formation and caliber irregularity. Patients with portal cholangiopathy may develop biliary complications including pruritus, obstructive jaundice, cholecystitis, and cholangitis [44-50]. (See "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management", section on 'Clinical manifestations'.)
SUMMARY
●Portal hypertension develops as a result of obstruction to flow within the portal venous system. It can be categorized as prehepatic, intrahepatic, or posthepatic based upon the site of obstruction to flow (table 1). As a general rule, the clinical consequences of portal hypertension are similar regardless of the cause or site of obstruction. Portal vein thrombosis (PVT) is the most common cause of extrahepatic portal vein obstruction. (See 'Introduction' above.)
●The incidence of PVT among patients without cirrhosis is unclear. It is thought to account for 5 to 10 percent of patients with portal hypertension in developed countries and up to a third of patients in resource-limited countries. (See 'Epidemiology' above.)
●Among patients with cirrhosis, PVT is common and is associated with the severity of the patient's liver disease. The prevalence of PVT is estimated to be less than 1 percent in patients with compensated cirrhosis, but it is 8 to 25 percent in patients who are candidates for liver transplantation. (See 'Epidemiology' above.)
●PVT in a patient with a previously healthy liver is thought to be due to inherited or acquired prothrombotic states (table 2). However, no apparent cause for PVT is identified in more than 25 percent of patients. (See 'Pathogenesis' above and "Overview of the causes of venous thrombosis" and "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors".)
●Among patients with cirrhosis, the pathogenesis of PVT is likely related to unbalanced hemostasis and slowing of portal flow.
●PVT can lead to complications such as intestinal ischemia, portal hypertension, and portal cholangiopathy. (See 'Complications' above.)
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