Inferior Vena Cava Thrombosis

Thrombosis within the inferior vena cava, usually by extension of lower limb or iliofemoral deep vein thrombosis (the commonest cause), or in situ. It is found in about 4% of patients with deep vein thrombosis and may extend to the renal and hepatic veins.

• Causes: extension of iliofemoral thrombosis, tumour thrombus (renal cell carcinoma, hepatocellular carcinoma, adrenal tumours, leiomyosarcoma), compression or invasion by retroperitoneal masses, congenital anomalies (agenesis or hypoplasia of the infrarenal inferior vena cava in about 5% of young patients with deep vein thrombosis), inferior vena cava filters (thrombosis in up to about 10 to 30% long term), hypercoagulable states (antiphospholipid syndrome, Behçet disease, paroxysmal nocturnal haemoglobinuria, myeloproliferative neoplasms), pregnancy, oestrogens, trauma and surgery, hepatic vein occlusion (Budd-Chiari syndrome), and membranous obstruction of the vena cava (more common in Africa and Asia).
• Level matters: infrarenal (leg symptoms), renal (nephrotic syndrome, acute kidney injury), suprarenal and hepatic (Budd-Chiari syndrome, liver failure), and right atrial extension.
• Consequences: pulmonary embolism, post-thrombotic syndrome, chronic venous insufficiency, kidney and liver injury, and death. Outcome depends on the cause and level.

• Bilateral leg swelling and pain (unilateral if the thrombus is partial), swelling of the lower abdomen, scrotum or labia, dilated superficial veins of the abdominal wall and flanks with upward flow, back or flank pain, haematuria or proteinuria (renal vein), ascites and tender hepatomegaly (hepatic vein), acute kidney injury, and features of pulmonary embolism.
• Phlegmasia cerulea dolens (a painful blue swollen limb) in extensive iliocaval thrombosis.
• Differential diagnosis: bilateral deep vein thrombosis without cava involvement, heart failure, nephrotic syndrome, cirrhosis, hypoalbuminaemia, lymphoedema, pelvic tumour compression, constrictive pericarditis, tricuspid regurgitation, abdominal compartment syndrome, pregnancy related oedema, drug induced oedema, and Budd-Chiari syndrome.
• Complications: pulmonary embolism, post-thrombotic syndrome, acute kidney injury, nephrotic syndrome, hepatic congestion and liver failure, recurrent thrombosis, and bleeding on anticoagulation.

• Duplex ultrasonography of the legs, iliac veins and cava (limited by bowel gas); contrast CT or CT venography (filling defect, tumour thrombus that enhances, anomalies, collaterals); MR venography; echocardiography for atrial extension; CT pulmonary angiography when embolism is suspected.
• Blood tests: D-dimer, full blood count with platelets, creatinine, electrolytes, albumin, urinalysis with protein quantification, liver function, coagulation.
• Thrombophilia and cause screen: antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, beta-2 glycoprotein I; repeat at 12 weeks), JAK2 V617F, flow cytometry for paroxysmal nocturnal haemoglobinuria, factor V Leiden, prothrombin gene mutation, protein C, protein S and antithrombin levels (interpret with care during acute thrombosis and heparin), HIV test, cancer screening with CT of chest, abdomen and pelvis, and assessment for Behçet disease and pulmonary artery aneurysm before anticoagulation in Behçet disease.

• Therapeutic anticoagulation for all patients, started at once:
  • Enoxaparin 1 mg/kg SC twice daily (or 1.5 mg/kg once daily; 1 mg/kg once daily when creatinine clearance is less than 30 mL/min), or unfractionated heparin 80 units/kg IV bolus then 18 units/kg/h (aPTT 1.5 to 2.5 times control) when creatinine clearance is less than 30 mL/min, bleeding risk is high, or intervention is planned.
  • Then rivaroxaban 15 mg twice daily with food for 21 days then 20 mg daily, or apixaban 10 mg twice daily for 7 days then 5 mg twice daily, or warfarin to INR 2.0 to 3.0 (at least 5 days of overlap and INR 2.0 or more for 24 hours).
  • Duration: at least 3 to 6 months for provoked thrombosis; 6 to 12 months or indefinite anticoagulation for unprovoked thrombosis, congenital cava anomaly, recurrent events, and persistent risk factors.
  • Cancer: enoxaparin 1 mg/kg twice daily, or apixaban 10 mg twice daily for 7 days then 5 mg twice daily, for at least 6 months and while cancer is active.
  • Antiphospholipid syndrome: warfarin to INR 2.0 to 3.0 (target 3.0 to 4.0 if thrombosis recurs on treatment); avoid direct oral anticoagulants, especially in triple positive disease.
  • Paroxysmal nocturnal haemoglobinuria: anticoagulation with a complement inhibitor (eculizumab) under haematology.
  • Behçet disease: immunosuppression (prednisolone 1 mg/kg/day, azathioprine 2.5 mg/kg/day, or cyclophosphamide pulses), and anticoagulate only after excluding pulmonary artery aneurysm.
  • Myeloproliferative neoplasm: hydroxyurea 15 to 30 mg/kg/day (specialist directed) plus anticoagulation.
  • Heparin induced thrombocytopenia: stop heparin, give argatroban 2 micrograms/kg/min IV (0.5 to 1 microgram/kg/min in hepatic impairment) or fondaparinux 7.5 mg SC daily (5 mg if under 50 kg, 10 mg if over 100 kg).
• Thrombus removal (acute thrombosis with symptoms for less than 14 days, severe symptoms, phlegmasia, renal vein thrombosis with kidney injury, or Budd-Chiari syndrome, low bleeding risk):
  • Catheter directed thrombolysis with alteplase 0.5 to 1 mg/h (maximum total about 20 to 40 mg) with fibrinogen monitoring (stop at less than 1 g/L), or pharmacomechanical or aspiration thrombectomy, with angioplasty and stenting of any underlying stenosis.
  • Surgical thrombectomy or resection for tumour thrombus (for example renal cell carcinoma extending into the cava, using cardiopulmonary bypass for atrial extension).
  • Contraindications to thrombolysis: active bleeding, stroke or intracranial surgery within 3 months, major surgery or trauma within 3 weeks, severe uncontrolled hypertension (greater than 180/110 mmHg), pregnancy (relative).
• Inferior vena cava filter only for acute proximal thrombosis or pulmonary embolism with an absolute contraindication to anticoagulation, or recurrent embolism despite therapeutic anticoagulation: retrievable filter, removed once anticoagulation is possible (usually within 3 months), since filters increase leg thrombosis.
• Chronic obstruction or membranous web: balloon angioplasty with stenting, or surgical membranotomy for membranous obstruction.
• Supportive care: compression stockings of 30 to 40 mmHg once pain allows, early ambulation, hydration, and dialysis for refractory hyperkalaemia, acidosis or fluid overload in acute kidney injury.
• Special groups:
  • Pregnancy: enoxaparin 1 mg/kg twice daily through pregnancy and for at least 6 weeks postpartum (minimum total 3 months); avoid warfarin and direct oral anticoagulants.
  • Congenital cava anomaly: lifelong anticoagulation in most patients.
  • Children: weight based enoxaparin 1 mg/kg twice daily (1.5 mg/kg twice daily in infants) with haematology input.
  • Elderly: dose reduce for renal function and monitor bleeding.
  • Obesity: dose by actual body weight.
• Red flags: chest pain or dyspnoea, blue painful limb, acute kidney injury, ascites with jaundice, bleeding, falling platelets on heparin.
• Follow up: review at 1 week, 1, 3 and 6 months; duplex ultrasonography or CT at 3 to 6 months to assess thrombus resolution; creatinine, liver function and full blood count; decide anticoagulant duration at 3 to 6 months; screen for post-thrombotic syndrome with the Villalta score.