In a patient with antiphospholipid syndrome presenting with ascites and splenomegaly, what is the most likely underlying cause and how should it be diagnosed and managed?

Antiphospholipid Syndrome with Ascites and Splenomegaly

Most Likely Underlying Cause

The combination of ascites and splenomegaly in a patient with antiphospholipid syndrome (APS) most likely indicates Budd-Chiari syndrome—hepatic venous outflow obstruction caused by thrombosis—which is a well-recognized thrombotic complication of APS. 1, 2, 3, 4

Budd-Chiari syndrome occurs when thrombosis obstructs hepatic venous outflow anywhere from the small hepatic venules to the inferior vena cava entrance into the right atrium, leading to portal hypertension, ascites, and splenomegaly. 1

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Diagnostic Workup

Immediate Diagnostic Paracentesis

• Perform diagnostic paracentesis immediately (within hours of presentation) to obtain ascitic fluid for cell count, albumin, total protein, and bedside inoculation into blood culture bottles. 5, 6
• Calculate the serum-ascites albumin gradient (SAAG): a SAAG ≥1.1 g/dL indicates portal hypertension with 97% accuracy and is consistent with Budd-Chiari syndrome. 5, 6, 7
• Check ascitic fluid neutrophil count to rule out spontaneous bacterial peritonitis (>250 cells/mm³), which occurs in approximately 15% of hospitalized cirrhotic patients. 8, 5, 6

Essential Blood Tests

• Measure serum albumin on the same day as paracentesis for accurate SAAG calculation. 6
• Obtain complete blood count (looking for thrombocytopenia, which is part of APS), liver function tests, renal function, and coagulation studies. 6
• Test for antiphospholipid antibodies: lupus anticoagulant, anticardiolipin IgG and IgM, and anti-β2-glycoprotein I antibodies to confirm APS diagnosis. 1, 2, 3

Imaging Studies

• Abdominal ultrasound with Doppler should evaluate hepatic vein patency, inferior vena cava caliber, liver appearance, splenomegaly, and portal vein flow. 8, 6
• Look specifically for reduced calibration or occlusion of hepatic venules and the intrahepatic segment of the inferior vena cava, which are characteristic findings in Budd-Chiari syndrome. 1, 4
• CT or MRI with venography may be needed if ultrasound is inconclusive to definitively visualize hepatic vein thrombosis. 1

Rule Out Other Causes

• Exclude hereditary hypercoagulable states (Factor V Leiden, prothrombin gene mutation, protein C/S deficiency, antithrombin deficiency) and myeloproliferative disorders. 1
• Consider tuberculous peritonitis if ascitic fluid shows lymphocyte predominance with high protein (>2.5 g/dL) and SAAG <1.1 g/dL, though this is less likely with confirmed APS and imaging showing venous obstruction. 7

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Management Strategy

Anticoagulation (Cornerstone of Treatment)

• Initiate therapeutic anticoagulation immediately with intravenous heparin followed by transition to warfarin (target INR 2-3) for all patients with Budd-Chiari syndrome secondary to APS. 1, 2, 3, 4
• Anticoagulation is the mainstay of treatment for all cases of Budd-Chiari syndrome with a demonstrable hypercoagulable state. 1
• Lifelong anticoagulation is required to prevent recurrent thrombosis. 1, 2

Management of Portal Hypertension and Ascites

• Initiate combined spironolactone (starting dose 100 mg daily) and furosemide (starting dose 40 mg daily) for ascites management. 8, 5
• Titrate diuretics every 3-5 days while maintaining a 100:40 mg ratio, up to maximum doses of spironolactone 400 mg/day and furosemide 160 mg/day. 5
• Impose strict sodium restriction of ≤2000 mg/day (≈88 mmol/day) to enhance diuretic responsiveness. 8, 5
• Large-volume therapeutic paracentesis is the preferred treatment for massive (grade III) ascites, with albumin replacement at 8 g per liter of fluid removed to prevent post-paracentesis circulatory dysfunction. 5

Interventional Procedures for Refractory Cases

• Transjugular intrahepatic portosystemic shunt (TIPS) should be considered when ascites becomes refractory to medical management (diuretics and sodium restriction). 1
• TIPS reduces portal hypertension and improves complications, but in APS patients there is a risk of shunt dysfunction secondary to thrombosis or stenosis due to endothelial dysfunction. 1
• Strict anticoagulation and regular follow-up after TIPS is mandatory, with reintervention (balloon dilation) if stent stenosis develops. 1

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Critical Pitfalls to Avoid

• Do not delay paracentesis for coagulopathy correction: routine fresh frozen plasma or platelet transfusion is not data-supported, and complications occur in only ~1% of procedures. 8, 5, 6
• Do not assume cirrhosis is the cause without imaging the hepatic veins—Budd-Chiari syndrome can present identically to cirrhotic ascites but requires fundamentally different treatment (anticoagulation). 1, 2
• Do not discontinue anticoagulation even if the patient is on aspirin alone for APS; therapeutic anticoagulation with warfarin is essential for Budd-Chiari syndrome. 1, 2, 4
• Monitor for stent dysfunction if TIPS is performed, as APS patients have higher rates of thrombosis and stenosis requiring reintervention. 1

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Prognosis and Long-Term Management

• Early recognition and treatment with anticoagulation can significantly improve survival in Budd-Chiari syndrome secondary to APS. 2
• Acute Budd-Chiari syndrome complicating APS generally has a poor outcome if not diagnosed and treated promptly, but tight anticoagulant therapy can lead to rapid clinical improvement. 4
• TIPS enables clinical improvement in cases where medical treatment is insufficient to control complications of portal hypertension. 1