WORKUP	Section 5 of 10
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Lab Studies:

• Examination of ascitic fluid provides useful clues to the diagnosis.

• Patients usually have high protein concentrations (>2 g/dL). This may not be present in persons with the acute form of Budd-Chiari syndrome.

• The WBC count is usually less than 500/mL.

• The serum ascites–albumin gradient is usually less than 1.1 (except in the acute forms of the disease).

• Routine biochemical test results are usually nonspecific. Mild elevations in serum aminotransferase and alkaline phosphatase levels are present in 25-50% of patients.

• Hematological studies should be performed to evaluate for a hypercoagulable state. See Polycythemia Vera; Thrombocytosis, Essential; Protein C Deficiency; Protein S Deficiency; and Myeloproliferative Disease for more information.

Imaging Studies:

• Ultrasound

• Thrombi can be visualized.

• Color-flow Doppler ultrasound is the preferred mode. Sensitivity and specificity are 85-90%.

• Magnetic resonance imaging (MRI) scanning with pulsed sequencing

• MRI images help in the assessment of hepatic venous blood flow.

• Sensitivity and specificity are 90%.

• Hepatic venography

• Thrombi are observed in hepatic veins.

• With venography, hepatic vein orifices cannot be cannulated.

Procedures:

• Liver biopsy

	TREATMENT	Section 6 of 10
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Medical Care: Medical therapy can be instituted for short-term, symptomatic benefit. Medical therapy alone is associated with a high 2-year mortality rate (80-85%).

• Management of ascites: See Ascites for more information.

• Anticoagulation

• Antithrombolytic therapy: This has been used in a few cases. Agents include streptokinase, urokinase, recombinant tissue plasminogen activator, and other modalities.

• Angioplasty: This can help relieve obstruction caused by membranous webs.

Surgical Care: Offer decompression of the hepatic vasculature if portal hypertension is the cause of the symptoms. Either surgery or a transjugular intrahepatic portosystemic shunt procedure can be performed.

Offer liver transplantation if decompensated liver cirrhosis is present (see Liver Transplantation).

Consultations:

• Gastroenterologist

• Hematologist

• Surgeon

• Radiologist

Diet: Recommend a low-sodium diet for the control of ascites.

	MEDICATION	Section 7 of 10
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Anticoagulation is needed in some patients, especially those with underlying hematological disorders as the cause of the syndrome.

Drug Category: Anticoagulants -- Prevent recurrent or ongoing thromboembolic occlusion.

Drug Name	Warfarin (Coumadin) -- Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to maintain an INR in the range of 2-3.
Adult Dose	5-15 mg/d PO qd for 2-5 d; adjust dose according to desired INR
Pediatric Dose	0.05-0.34 mg/kg/d PO; adjust dose according to desired INR
Contraindications	Documented hypersensitivity; severe liver or kidney disease; open wounds; GI ulcers
Interactions	Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate Medications that may increase anticoagulant effects include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac
Pregnancy	X - Contraindicated in pregnancy
Precautions	Do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes; patients who have protein C or S deficiency are at risk of developing skin necrosis

Drug Category: Fibrinolytic agents -- Used to dissolve a pathologic intraluminal thrombus or embolus that has not been dissolved by the endogenous fibrinolytic system. Also used for the prevention of recurrent thrombus formation and for the rapid restoration of hemodynamic disturbances.

Drug Name	Streptokinase (Kabikinase, Streptase) -- Acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots, fibrinogen, and other plasma proteins. Increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 h occurs with intravenous infusion.
Adult Dose	Not established; can be administered locally via catheter or IV Local: 7500 U/h IV: 100,000 U/h after loading dose of 250,000 U bolus
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; active internal bleeding, intracranial neoplasm, aneurysm, diathesis, or severe uncontrolled arterial hypertension
Interactions	Antifibrinolytic agents may decrease effects; heparin, warfarin, and aspirin may increase risk of bleeding
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in severe hypertension, IM administration of medications, or trauma or surgery in the previous 10 d; measure hematocrit, platelet count, aPTT, TT, PT, or fibrinogen levels before therapy is implemented; either TT or aPTT should be less than twice the normal control value following infusion of streptokinase and before instituting or reinstituting heparin; do not take blood pressure in lower extremities because may dislodge possible deep vein thrombi; PT, aPTT, TT, or fibrinogen should be monitored 4 h after initiation of therapy

Drug Name	Urokinase (Abbokinase) -- Direct plasminogen activator that acts on the endogenous fibrinolytic system and converts plasminogen to the enzyme plasmin, which, in turn, degrades fibrin clots, fibrinogen, and other plasma proteins. Most often used for local fibrinolysis of thrombosed catheters and superficial vessels. Advantage is that agent is nonantigenic. However, more expensive than streptokinase and thus limits use. When used for local fibrinolysis, urokinase is given as local infusion directly into area of thrombus and with no bolus given. Dose should be adjusted to achieve clot lysis or patency of affected vessel.
Adult Dose	Can be given locally or systemically Loading dose: 4400 U/kg IV over 10 min and increase to 6000 U/kg/h Maintenance dose: 4400-6000 U/kg/h IV
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; internal bleeding, recent trauma, history of intracranial or intraspinal surgery or trauma, cerebrovascular accident, and intracranial neoplasm
Interactions	Thrombolytic enzymes, alone or in combination with anticoagulants and antiplatelets, may increase risk of bleeding complications
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in patients receiving IM administration of medications, severe hypertension, and trauma or surgery in previous 10 d; to avoid dislodging possible deep vein thrombi, do not measure blood pressure in lower extremities; monitor therapy by measuring PT, aPTT, TT, or fibrinogen level approximately 4 h after initiation of therapy

Drug Name	Alteplase (Activase) -- Tissue plasminogen activator used in management of acute myocardial infarction, acute ischemic stroke, and pulmonary embolism. Safety and efficacy with concomitant administration of heparin or aspirin during first 24 h after symptom onset have not been investigated.
Adult Dose	0.25-0.50 mg/kg IV over 60 min
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; active internal bleeding, cerebrovascular accident or stroke within last 2 mo, intracranial or intraspinal surgery or trauma, intracranial hemorrhage upon pretreatment evaluation, possible subarachnoid hemorrhage, intracranial neoplasm, arteriovenous malformation or aneurysm, bleeding diathesis, or severe uncontrolled hypertension
Interactions	Anticoagulants and antiplatelets may increase risk of bleeding; may give heparin with and after alteplase infusions to reduce risk of rethrombosis; either heparin or alteplase may cause bleeding complications
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor for bleeding, especially at arterial puncture sites, with coadministration of vitamin K antagonists; control and monitor blood pressure frequently during and following administration (when managing acute ischemic stroke); do not use >0.9 mg/kg to manage acute ischemic stroke; doses >0.9 mg/kg may cause ICH

	FOLLOW-UP	Section 8 of 10
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Further Inpatient Care:

• Gastroscopy should be performed to help rule out the presence of esophageal and gastric varices. If present, these may be obliterated with banding or sclerotherapy. Nonselective beta-blockers (eg, propranolol, nadolol) can be administered for primary prophylaxis against variceal bleeding.

• Electrolyte levels should be monitored closely because diuretics and other factors can cause electrolyte imbalances.

• Monitor prothrombin time and activated partial thromboplastin time once anticoagulation is started. These should be maintained within the therapeutic range.

Further Outpatient Care:

• Long-term anticoagulation is often needed, and it may also be needed after liver transplantation.

Transfer:

• Once a patient is determined to be a transplant candidate, transfer to a liver transplant unit.

Complications:

• Complications secondary to hepatic decompensation

• Hepatic encephalopathy

• Variceal hemorrhage

• Hepatorenal syndrome

• Portal hypertension

• Complications secondary to hypercoagulable state

Prognosis:

• The natural history is not well known. The following factors have been associated with a good prognosis:

• Younger age at diagnosis

• Low Child-Pugh score

• Absence of ascites or easily controlled ascites

• Low serum creatinine level

• A formula to calculate the prognostic index has been proposed. A score less than 5.4 is associated with a good prognosis. The formula to calculate the prognostic index is as follows:

  Prognostic index = (ascites score X 0.75) + (Pugh score X 0.28) + (age X 0.037) + (creatinine level X 0.0036)

• Prognosis is poor in patients with Budd-Chiari syndrome who remain untreated. Death results from progressive liver failure in 3 months to 3 years from the time of diagnosis.

• The 5-year survival rate is 38-87% following portosystemic shunting. The actuarial 5-year survival rate following liver transplantation is 70%.

	MISCELLANEOUS	Section 9 of 10
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Medical/Legal Pitfalls:

• Failure to perform hematological studies to evaluate for a hypercoagulable state

• Failure to offer long-term anticoagulation if indicated

• Failure to offer liver transplantation if indicated

• Failure to decompress the hepatic vasculature if portal hypertension is the cause of symptoms

	BIBLIOGRAPHY	Section 10 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

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