Phlegmasia Cerulea Dolens

Phlegmasia cerulea dolens is massive iliofemoral deep vein thrombosis that obstructs venous outflow of the limb and its collaterals, causing painful swelling, cyanosis, arterial compromise, compartment syndrome and venous gangrene. It is a limb threatening and life threatening emergency.

Epidemiology. It is a rare complication of proximal deep vein thrombosis (under 1 to 2%). Limb loss occurs in 20 to 50%, and mortality is 20 to 40%, mainly from pulmonary embolism and underlying disease.

Causes and associations. Malignancy (most often), hypercoagulable states, pregnancy and the puerperium, heparin induced thrombocytopenia, May-Thurner compression, inferior vena cava filter thrombosis, central line, surgery, immobility, antiphospholipid syndrome and oral contraceptives.

Pathophysiology. Thrombosis of the major deep veins and collateral veins raises venous pressure, causing massive fluid sequestration (up to 6 L), hypovolaemia, tissue oedema and rising compartment pressure. Arterial inflow falls, producing ischaemia and venous gangrene.

Presentation is sudden severe pain, tense swelling of the whole limb, blue purple discolouration, bullae, reduced sensation and weakness, and loss of arterial pulses (Doppler signals may persist). Shock from fluid sequestration is common. Features of pulmonary embolism may be present.

Red flags.

• Cyanosis, bullae, motor or sensory loss.
• Absent distal pulses or compartment syndrome.
• Hypotension or signs of pulmonary embolism.

Duplex ultrasound (iliofemoral thrombus extent), CT venography or MR venography to define the extent and any compressive lesion, and arterial duplex to exclude arterial occlusion. Check full blood count and platelets (heparin induced thrombocytopenia), coagulation, D-dimer, creatinine, creatine kinase, potassium, lactate and thrombophilia tests (before anticoagulation where possible). Look for malignancy.

Differential diagnosis. Acute arterial occlusion, cellulitis, compartment syndrome from other causes, lymphoedema, ruptured Baker cyst and heart failure.

Anticoagulation immediately. Unfractionated heparin 80 units/kg IV bolus (or 5000 units) then 18 units/kg/h, adjusted to anti-factor Xa 0.3 to 0.7 units/mL or activated partial thromboplastin time. If heparin induced thrombocytopenia is present, use argatroban 2 microgram/kg/min (0.5 to 1.2 microgram/kg/min in liver impairment) or bivalirudin.

Limb and resuscitation measures. Elevate the limb, give IV fluid for hypovolaemia (crystalloid 500 mL boluses), analgesia, and oxygen. Avoid compression in the acute phase.

Thrombus removal (first line for limb threat).

• Catheter directed thrombolysis with alteplase 0.5 to 1 mg/h (0.01 mg/kg/h in some regimens) for 12 to 24 hours with heparin 500 units/h, with fibrinogen and haemoglobin checks, or pharmacomechanical thrombectomy.
• Surgical venous thrombectomy with or without arteriovenous fistula when thrombolysis is contraindicated or has failed.
• Contraindications to lysis: recent surgery, bleeding, stroke or intracranial disease.

Fasciotomy. For compartment syndrome or after revascularisation with high pressures.

Inferior vena cava filter. Only when anticoagulation is contraindicated, or when pulmonary embolism recurs despite therapy.

Underlying cause. Stent the compressed vein (May-Thurner), and treat malignancy and thrombophilia.

Long term anticoagulation. At least 3 to 6 months, and longer for malignancy or unprovoked disease: rivaroxaban 15 mg orally twice daily for 21 days then 20 mg daily, or apixaban 10 mg twice daily for 7 days then 5 mg twice daily. In malignancy, apixaban or low molecular weight heparin (enoxaparin 1 mg/kg every 12 hours). Reduce or avoid with eGFR under 30 mL/min.

Monitoring. Limb perfusion and compartments hourly, platelets (day 5 to 10), anti-factor Xa, haemoglobin, fibrinogen and creatinine.

Referral and escalation. Vascular surgery and interventional radiology at once.

Special groups. In pregnancy, use low molecular weight heparin (enoxaparin 1 mg/kg every 12 hours), and avoid direct oral anticoagulants and warfarin. In malignancy, use low molecular weight heparin or apixaban.