May Thurner Syndrome

Compression of the left common iliac vein between the overlying right common iliac artery and the lumbar spine, which causes venous outflow obstruction, intraluminal webs or spurs from chronic intimal fibrosis, and a high risk of left iliofemoral deep vein thrombosis.

• Anatomical compression of more than 50% is present in about 20 to 25% of the general population and is usually asymptomatic. The syndrome is symptomatic in a small minority. It is found in about 18 to 50% of patients with left iliofemoral thrombosis (higher in young women). Women are affected about 2 to 3 times as often as men, usually between ages 20 and 40.
• Triggers: oral contraceptives, pregnancy and the puerperium, prolonged immobility, dehydration, surgery, long haul travel and inherited thrombophilia.
• Natural history if untreated: chronic left leg swelling, venous claudication and venous ulcer, pulmonary embolism in a sizeable minority, and post-thrombotic syndrome in up to about 70% after iliofemoral thrombosis. Recurrence after anticoagulation alone is common.

• Three presentations: asymptomatic compression found on imaging; chronic venous disease of the left leg (swelling, varicose veins, venous claudication, skin changes, ulcer); and acute left iliofemoral deep vein thrombosis (sudden swelling of the whole leg, pain, erythema, collateral veins, phlegmasia cerulea dolens with a painful blue leg).
• Left leg swelling is greater than the right. Pelvic congestion symptoms and scrotal or labial swelling can occur.
• Differential diagnosis: uncomplicated deep vein thrombosis without compression, lymphoedema, pelvic mass or tumour compressing the vein, retroperitoneal fibrosis, inferior vena cava abnormality, cellulitis, post-thrombotic syndrome, heart failure, and Baker cyst.
• Complications: pulmonary embolism, post-thrombotic syndrome, recurrent thrombosis, phlegmasia cerulea dolens with limb threat, venous ulcer, and complications of anticoagulation and stenting.

• Duplex ultrasonography of the leg and iliac veins (loss of respiratory phasicity in the common femoral vein, monophasic flow, collateral flow, acute thrombus).
• CT venography or MR venography: compression of the left common iliac vein of more than 50%, collaterals, web or spur, and thrombus; pelvic MRI to exclude a mass.
• Venography with intravascular ultrasound is the reference test: area stenosis of more than 50%, or a pressure gradient greater than 2 to 3 mmHg across the lesion.
• Blood tests: full blood count, creatinine, D-dimer, coagulation, and thrombophilia testing (lupus anticoagulant, anticardiolipin and beta-2 glycoprotein I antibodies, factor V Leiden, prothrombin gene mutation, protein C, protein S, antithrombin) where it would alter management; pregnancy test; CT pulmonary angiography for suspected embolism.

• Acute iliofemoral deep vein thrombosis:
  • Immediate therapeutic anticoagulation: enoxaparin 1 mg/kg SC twice daily (or 1.5 mg/kg daily; 1 mg/kg 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) before intervention or in renal failure, 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).
  • Early thrombus removal for symptoms of less than 14 days (up to 21 days selected), low bleeding risk, good functional status and life expectancy of more than 1 year: catheter directed thrombolysis with alteplase 0.5 to 1 mg/h (maximum total about 20 to 40 mg) through a multi-side-hole catheter with fibrinogen monitoring (stop at less than 1 g/L), or pharmacomechanical or aspiration thrombectomy; then angioplasty and stenting of the left common iliac vein with self-expanding venous stents (typically 14 to 16 mm), landing in the inferior vena cava when needed.
  • Phlegmasia cerulea dolens: urgent thrombectomy or thrombolysis with fasciotomy for compartment syndrome.
  • 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).
• Anticoagulation after stenting: at least 3 to 6 months of warfarin (INR 2.0 to 3.0) or a direct oral anticoagulant (rivaroxaban 20 mg daily or apixaban 5 mg twice daily); extend to 12 months or indefinitely when there is thrombophilia, a prior event or an unprovoked presentation; antiplatelet therapy (aspirin 75 to 100 mg daily) when anticoagulation is stopped.
• Chronic symptomatic disease:
  • Compression stockings of 30 to 40 mmHg, leg elevation, exercise, weight control, and venous ulcer care.
  • Stenting for severe symptoms (venous claudication, ulcer, refractory swelling) or after recurrent thrombosis: symptom relief in about 80 to 90%, primary patency about 90% at 1 to 2 years.
  • Open surgical bypass (such as cross pubic venous bypass) only when stenting fails.
• Asymptomatic compression: no treatment; do not stent. Counsel on hydration, mobility and avoidance of oestrogen containing contraception, and give prophylaxis in high risk settings (enoxaparin 40 mg SC daily and stockings during surgery, prolonged immobility or pregnancy).
• Contraception: progestogen only methods (levonorgestrel intrauterine system, etonogestrel implant); avoid oestrogen.
• Complications of stenting: stent thrombosis (about 5 to 10%), restenosis, migration, perforation, and bleeding.
• Special groups:
  • Pregnancy: enoxaparin 1 mg/kg twice daily for treatment, continued at least 6 weeks postpartum (minimum total 3 months); prophylactic enoxaparin 40 mg daily with prior thrombosis; avoid warfarin and direct oral anticoagulants; delay stenting until after delivery.
  • Young women on oral contraceptives: stop oestrogen immediately.
  • Children and adolescents: rare; anticoagulation weight based; stenting in specialist centres.
  • Cancer: enoxaparin 1 mg/kg twice daily or apixaban 5 mg twice daily after loading for at least 6 months.
  • Renal impairment: unfractionated heparin when creatinine clearance is less than 30 mL/min.
• Red flags: sudden swelling, blue discolouration, severe pain, chest pain or dyspnoea, bleeding, falling platelets on heparin.
• Follow up: review at 1 week, 1, 3 and 6 months; duplex ultrasonography of the stent at 1, 6 and 12 months then yearly; Villalta score; anticoagulant review at each visit.