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The Budd - Chiari syndrome is a heterogeneous group of disorders characterized by hepatic venous outflow obstruction at the level of the hepatic venules, the large hepatic veins, the inferior vena cava, or the right atrium. Hepatic veno-occlusive disease refers to obstruction of hepatic venous outflow at the level of the central or sublobular hepatic veins, or both.Pathogenesis: Obstruction of the hepatic venous outflow tract results in increased hepatic sinusoidal pressure and portal hypertension. In the early stages, portal venous perfusion of the liver is decreased, which may result in portal venous thrombosis. The ensuing venous stasis and congestion lead to hypoxic damage to adjacent hepatic parenchymal cells. Furthermore, the ischemic injury to the sinusoidal lining cells results in the release of free radicals, and oxidative injury to the hepatocytes ensues. These mechanisms culminate in the development of hepatocyte necrosis in the centrilobular regions (Figure 1), with progressive centrilobular fibrosis, nodular regenerative hyperplasia, and ultimately, cirrhosis of the liver.4 However, if the hepatic sinusoidal pressure is reduced by the creation of a portosystemic shunt or by the development of a portal venous collateral system, liver function improves. Factors that confer a predisposition to the development of the Budd–Chiari syndrome, including hypercoagulable states, both hereditary and acquired, and a variety of other causes, can be identified in about 75 percent of patients (Table 1). The presence of multiple causes in the same patient is increasingly recognized. Hematologic abnormalities, particularly myeloproliferative disorders, are the most common causes of the Budd–Chiari syndrome. Polycythemia vera accounts for between 10 and 40 percent of cases of the syndrome, whereas essential thrombocythemia and myelofibrosis are less prevalent causes. Endogenous erythroid-colony formation may be seen in up to 87 percent of patients thought to have idiopathic Budd–Chiari syndrome, suggesting that the majority of patients in whom the cause of the Budd–Chiari syndrome is not apparent have a myeloproliferative disorder.Other causes of the syndrome include paroxysmal nocturnal hemoglobinuria,the antiphospholipid syndrome,and inherited deficiencies of protein C, protein S, and antithrombin III. In a number of patients with the Budd–Chiari syndrome, protein C deficiency has also been associated with a myeloproliferative disorder. Levels of protein C, protein S, and antithrombin III may also be low in the presence of an acute thrombus and in patients with liver disease, including the Budd–Chiari syndrome.In patients with inherited deficiencies of these proteins, however, the levels are well below 10 to 20 percent of normal. Normal levels of factor II (prothrombin) and factor VII in the patient or a deficiency of protein C and protein S in family members indicates an inherited thrombophilia.The factor V Leiden mutation, the prothrombin-gene mutation, and the methylenetetrahydrofolate reductase mutation have also been noted in patients with the Budd–Chiari syndrome. Although some of these mutations, when present alone, may not confer a predisposition to hepatic venous thrombosis, the association of any one of them with another predisposing factor may result in the Budd–Chiari syndrome.The relative risk of hepatic-vein thrombosis among women who use oral contraceptives is 2.37, which is similar to their relative risk of stroke, myocardial infarction, and venous thromboembolism. Hepatic-vein thrombosis has been described both in pregnancy and in the immediate postpartum period. It is, however, becoming increasingly clear that many patients in whom the Budd–Chiari syndrome develops in association with the use of oral contraceptives or pregnancy may also have an underlying thrombophilia, either inherited or acquired.