Post Thrombotic Syndrome

Chronic venous disease that follows deep vein thrombosis, caused by residual venous obstruction, valvular reflux and calf muscle pump failure, leading to ambulatory venous hypertension. It develops in about 20 to 50% of patients within 2 years of a proximal deep vein thrombosis, severe in about 5 to 10%, with venous ulcer in about 1 to 4%.

• Risk factors: iliofemoral (proximal) thrombosis, ipsilateral recurrence, persistent symptoms 1 month after the event, obesity, older age, varicose veins, inadequate anticoagulation in the first 3 months (sub-therapeutic INR), and residual thrombus at 6 months.
• It reduces quality of life as much as chronic heart or lung disease and results in high health costs.

• Heaviness, aching, pain, cramps, itching and paraesthesia in the affected leg, worse after standing or walking and relieved by lying with the leg raised.
• Signs: pitting oedema, hyperpigmentation, venous eczema, lipodermatosclerosis, varicose veins, pain on calf compression, redness, and in severe cases venous ulcer. Iliofemoral disease causes venous claudication (bursting thigh or groin pain on walking).
• Differential diagnosis: recurrent deep vein thrombosis, lymphoedema, lipoedema, cellulitis, heart failure, renal or hepatic oedema, hypothyroidism, drug induced oedema (amlodipine), primary chronic venous disease, arthritis, Baker cyst and peripheral arterial disease.
• Complications: venous ulcer, chronic pain, impaired quality of life, recurrent thrombosis, cellulitis and disability.

• Diagnose clinically at least 3 to 6 months after deep vein thrombosis, once acute symptoms have settled, with a history of thrombosis.
• Villalta score: five symptoms (heaviness, pain, cramps, itching, paraesthesia) and six signs (pretibial oedema, skin induration, hyperpigmentation, redness, venous ectasia, pain on calf compression), each scored 0 to 3; a total of 5 or more, or an ulcer, confirms the syndrome. Mild is 5 to 9, moderate 10 to 14, severe 15 or more or ulcer.
• Duplex ultrasonography for residual obstruction, reflux (greater than 0.5 seconds in superficial veins, greater than 1.0 second in femoral and popliteal veins), and to exclude recurrent thrombosis.
• CT venography, MR venography or intravascular ultrasound to define iliocaval obstruction when intervention is considered. Ankle brachial pressure index before compression.
• Blood tests: full blood count, creatinine, albumin, thyroid function; thrombophilia testing only when it would change management (unprovoked thrombosis at a young age, family history, recurrent events).

• Prevention at the time of deep vein thrombosis:
  • Effective anticoagulation for at least 3 months: rivaroxaban 15 mg twice daily with food for 21 days then 20 mg daily; apixaban 10 mg twice daily for 7 days then 5 mg twice daily; or enoxaparin 1 mg/kg SC twice daily overlapped with warfarin (INR 2.0 to 3.0, at least 5 days of overlap), and keep INR in range.
  • Early ambulation, and compression stockings for symptoms.
  • Catheter directed thrombolysis or pharmacomechanical thrombectomy for selected patients with acute iliofemoral deep vein thrombosis (symptoms for less than 14 days, low bleeding risk, good functional status), which lowers the frequency of the syndrome at the cost of more bleeding.
• Symptomatic treatment:
  • Knee high compression stockings of 30 to 40 mmHg, worn daily and replaced every 3 to 6 months; intermittent pneumatic compression for severe oedema.
  • Leg elevation, calf exercise and walking, weight loss, skin care with emollients, and avoidance of prolonged standing.
  • Analgesia: paracetamol 1 g four times daily; avoid long term NSAIDs.
  • Micronised purified flavonoid fraction 500 mg twice daily or pentoxifylline 400 mg three times daily may help (evidence is limited).
  • Diuretics only for cardiac or renal oedema; they are not useful for venous oedema.
• Venous ulcer: compression bandaging at 35 to 40 mmHg changed weekly, wound care, and correction of superficial reflux by endovenous ablation or of deep venous obstruction by stenting (ankle brachial pressure index checked first).
• Intervention for severe or refractory disease:
  • Iliac or iliofemoral vein obstruction with severe symptoms or ulcer: balloon angioplasty and stenting with self-expanding venous stents; primary patency about 80 to 90% at 1 to 2 years, ulcer healing about 60 to 70%, with symptom improvement in most. Give anticoagulation after stenting (warfarin INR 2.0 to 3.0 or a direct oral anticoagulant) for at least 3 to 6 months, and longer in high risk patients.
  • Superficial reflux contributing to symptoms: endovenous ablation or foam sclerotherapy.
  • Deep venous reconstruction (valve repair, transposition, or bypass) for selected patients at specialist centres.
• Anticoagulation for recurrence: lifelong in unprovoked, recurrent or high risk thrombosis.
• Special groups:
  • Pregnancy: use graduated stockings, enoxaparin 40 mg SC daily prophylaxis through pregnancy and 6 weeks postpartum after a prior deep vein thrombosis; avoid warfarin and direct oral anticoagulants.
  • Children: rare; compression and mobility.
  • Elderly: help with stocking application, and check arterial supply (ankle brachial pressure index) first.
  • Renal impairment: adjust anticoagulant dose (reduce enoxaparin when creatinine clearance is less than 30 mL/min).
  • Obesity and cancer: weight loss and cancer directed therapy.
• Red flags: new unilateral swelling (recurrent thrombosis), painful blue leg, rapidly enlarging ulcer, fever with spreading redness, chest pain or dyspnoea.
• Follow up: review at 3, 6 and 12 months after the thrombosis with Villalta score; yearly thereafter; stocking check every 3 to 6 months; vascular referral for severe disease or ulcer.