Venous Thoracic Outlet Syndrome

Venous thoracic outlet syndrome is compression of the subclavian vein at the costoclavicular space, causing stenosis and thrombosis. Effort thrombosis (Paget-Schroetter syndrome) is the acute thrombotic presentation, in a young person after repeated or strenuous arm activity.

Venous thoracic outlet syndrome accounts for about 3 to 5% of thoracic outlet syndrome. Effort thrombosis has an incidence of about 1 to 2 cases in every 100,000 people each year and forms a small share of upper limb deep vein thrombosis, most of which is catheter related. It affects mainly young, active people, with men affected more than women, and the dominant arm is more often involved.

Predisposing factors are overhead and throwing sports (swimming, baseball, weightlifting, rowing), repetitive occupational activity, a hypertrophied anterior scalene or subclavius muscle, a costoclavicular ligament, an anomalous first rib, and a congenital web. Thrombophilia is found in a minority.

Untreated disease causes post-thrombotic syndrome with arm swelling, pain and fatigue in a substantial share of patients. Pulmonary embolism complicates about 5 to 10%.

Pathophysiology.

The subclavian vein passes between the clavicle and the first rib, anterior to the scalene muscle. Arm elevation narrows this space, and repeated compression injures the vein wall, causing intimal fibrosis, perivenous scarring and stenosis.

Stasis and endothelial injury lead to thrombosis, often after a bout of unusual exertion. Thrombus extends into the axillary and brachial veins and can propagate toward the innominate vein. Collateral veins develop around the shoulder and chest wall.

Even after the thrombus is cleared, an underlying stenosis persists unless the compression is relieved, which explains the high rate of re-thrombosis with anticoagulation alone.

Sudden swelling, heaviness and aching of the arm, often after exertion, with blue or purple discolouration, warmth and tenderness along the axillary vein. Distended superficial veins over the shoulder and anterior chest wall (collaterals) are typical. Intermittent arm swelling and discolouration with elevation can precede thrombosis (positional venous obstruction). Pain on use of the arm and arm fatigue persist. Chest pain and dyspnoea suggest pulmonary embolism.

• Duplex ultrasound: non-compressible, thrombosed subclavian or axillary vein, with loss of respiratory variation and phasic flow. The subclavian vein beneath the clavicle is difficult to image, so a normal result does not exclude thrombosis when suspicion is high.
• Contrast venography is the reference test, and is performed at the start of catheter directed treatment. CT or MR venography shows thrombus, stenosis and bony anatomy, and compression with the arm abducted.
• Chest radiograph for cervical rib or first rib abnormality. CT chest or CT pulmonary angiography if pulmonary embolism is suspected.
• Blood tests: full blood count, creatinine, coagulation screen, thrombophilia screen when indicated (antiphospholipid antibodies, factor V Leiden and prothrombin variants, protein C and S and antithrombin after the acute phase). D-dimer has a limited role.
• Search for alternative causes: central venous catheter, pacemaker leads, malignancy (including breast and lung cancer), and mediastinal mass.

Differential diagnosis.

• Catheter- or device related upper limb thrombosis.
• Superior vena cava obstruction, malignant extrinsic compression and lymphoedema.
• Cellulitis, muscle injury or haematoma, and cardiac failure with arm swelling.
• Arterial and neurogenic thoracic outlet syndrome.

Principles. Treat the thrombus early to restore patency, anticoagulate, then relieve the compression with surgery to prevent recurrence.

Immediate anticoagulation.

• Enoxaparin 1 mg/kg subcutaneously every 12 hours (1 mg/kg once daily when creatinine clearance is under 30 mL/min), or unfractionated heparin 80 units/kg intravenous bolus then 18 units/kg/h (aPTT 1.5 to 2.5 times control), or apixaban 10 mg orally twice daily for 7 days then 5 mg twice daily, or rivaroxaban 15 mg orally twice daily with food for 21 days then 20 mg once daily with food.
• Check haemoglobin, platelets and creatinine at baseline and at least weekly in the first month.

Thrombus removal (symptoms under 14 days, patient fit, no contraindication).

• Catheter directed or pharmacomechanical thrombolysis with alteplase 0.5 to 1 mg/h (usual total up to about 40 mg) with low dose heparin 500 units/h, with fibrinogen and clinical review every 6 hours, until flow is restored (often 12 to 48 hours). Success is high within the first 2 weeks and falls steadily afterwards.
• Absolute contraindications are previous intracranial haemorrhage, ischaemic stroke in the last 6 months, intracranial neoplasm, active bleeding, and major surgery or trauma in the last 3 weeks.
• Mechanical thrombectomy and aspiration are alternatives. Balloon angioplasty and stenting before decompression are avoided because stents compress and fracture in the outlet. Angioplasty after rib resection is used for residual stenosis.

Surgical decompression.

• First rib resection, with scalenectomy, venolysis (removal of fibrous tissue around the vein) and sometimes vein patch or bypass, via a transaxillary, supraclavicular or paraclavicular approach. Timing: during the same admission (within days to 2 weeks) or after 4 to 12 weeks of anticoagulation. Both approaches have high success when the vein is cleared.
• Perioperative: cefazolin 2 g intravenously within 60 minutes before incision (3 g when weight is over 120 kg), and hold anticoagulation for the shortest time that bleeding risk requires. Intraoperative or post-operative venography with balloon angioplasty of any residual stenosis.
• Complications are pneumothorax, brachial plexus injury, bleeding, chylous leak and recurrent thrombosis.

Anticoagulation duration.

• At least 3 months after thrombosis, continuing until decompression and venographic patency are confirmed, usually 1 to 3 months after surgery. Longer treatment applies for persistent thrombophilia or residual stenosis.
• Apixaban 5 mg twice daily (after the initial 7 days of 10 mg twice daily) or rivaroxaban 20 mg once daily with food; reduce rivaroxaban to 15 mg once daily when creatinine clearance is 15 to 49 mL/min; avoid direct oral anticoagulants with antiphospholipid syndrome, where warfarin to INR 2.0 to 3.0 is used.

Symptomatic care. Arm elevation, early return to normal activity once anticoagulated, and graduated compression sleeve for persistent swelling. Avoid heavy overhead activity until recovery.

Non-thrombotic (positional) compression. Intermittent venous obstruction without thrombosis: surgical decompression for persistent symptoms, with venography and angioplasty as needed.

Monitoring. Duplex at 1 week, 1 month, 3 months and 12 months. Venography after decompression at 2 to 6 weeks (and with symptoms). Full blood count and creatinine on anticoagulation, and assessment for post-thrombotic syndrome at 3 and 12 months.

Referral and escalation. Refer every suspected effort thrombosis to a vascular surgeon or thoracic outlet service within 24 hours, since the window for lysis is short. Same day referral for phlegmasia, pulmonary embolism, or extensive thrombus.

Special groups.

• Pregnancy: treat with enoxaparin 1 mg/kg subcutaneously every 12 hours with anti-Xa monitoring; avoid warfarin and direct oral anticoagulants; defer decompression until after delivery unless symptoms are disabling.
• Athletes: return to sport after surgery and healing, usually at 3 months, once patency is documented.
• Kidney impairment: give enoxaparin 1 mg/kg once daily when creatinine clearance is under 30 mL/min; reduce rivaroxaban to 15 mg once daily at creatinine clearance 15 to 49 mL/min; avoid rivaroxaban and use apixaban only with specialist advice when creatinine clearance is under 15 mL/min; limit contrast volume.
• Region specific: where thrombolysis or venography is unavailable, anticoagulation with early surgical referral gives reasonable results, though recurrence is more likely.