Upper Extremity Deep Vein Thrombosis

Thrombosis of the deep veins of the arm and shoulder girdle (brachial, axillary, subclavian and sometimes internal jugular and brachiocephalic veins). It makes up about 4 to 10% of all deep vein thrombosis, with an incidence of about 3 per 100,000 per year, and is rising with the use of central lines and devices.

• Two types:
  • Secondary (about 70 to 80%): central venous catheters and peripherally inserted central catheters, pacemaker and defibrillator leads, dialysis catheters, cancer (the vein is invaded or compressed, or the cancer is hypercoagulable), surgery, trauma, infection, ovarian hyperstimulation, oestrogen therapy, thrombophilia, and intravenous drug use.
  • Primary (about 20 to 30%): effort thrombosis, thoracic outlet compression, and idiopathic.
• Complications: pulmonary embolism (about 3 to 7%), post-thrombotic syndrome (about 5 to 20%), recurrent thrombosis (about 2 to 5%, higher with persistent catheter or cancer), catheter dysfunction and infection. Mortality mostly reflects the underlying disease, especially cancer.

• Arm swelling, aching, heaviness, tightness, discolouration (cyanosis or erythema), warmth, dilated collateral veins on the shoulder and chest wall, and venous distension of the arm. Neck or facial swelling suggests brachiocephalic or superior vena cava extension. Some cases are asymptomatic and found by catheter malfunction or chance.
• Fever and local tenderness at the catheter exit site suggest catheter related infection. Dyspnoea and pleuritic pain suggest pulmonary embolism.
• Differential diagnosis: cellulitis, lymphoedema, haematoma, superficial vein thrombosis, axillary vein compression by lymphadenopathy or tumour, superior vena cava syndrome, heart failure, arterial thoracic outlet syndrome, musculoskeletal pain, and Pancoast tumour.
• Complications: pulmonary embolism, post-thrombotic syndrome, catheter related bloodstream infection, loss of venous access, superior vena cava syndrome, and recurrent thrombosis.

• Compression ultrasonography with colour Doppler of the arm veins (non-compressible vein, absent flow, loss of respiratory variation and cardiac pulsatility in the subclavian vein). Ultrasonography is less sensitive for the central veins (innominate and medial subclavian), so a negative result with high suspicion needs CT or MR venography, or contrast venography.
• D-dimer is less reliable than in the leg. A clinical score is helpful (venous catheter or pacemaker present, localised venous pain, unilateral pitting oedema each add one point; subtract one if another diagnosis is as likely; a score of 0 or less with a negative D-dimer makes thrombosis unlikely).
• Check catheter position (chest X-ray), blood cultures if febrile, full blood count with platelets, creatinine and coagulation. Assess for cancer when unprovoked. Thrombophilia tests (lupus anticoagulant, anticardiolipin and beta-2 glycoprotein I antibodies, factor V Leiden, prothrombin variant, protein C and S, antithrombin) for primary thrombosis, a young patient or a family history.
• CT pulmonary angiography if pulmonary embolism is suspected.

• Anticoagulation for at least 3 months (all patients):
  • Apixaban 10 mg twice daily for 7 days then 5 mg twice daily, or rivaroxaban 15 mg twice daily with food for 21 days then 20 mg once daily; or enoxaparin 1 mg/kg SC twice daily (1 mg/kg once daily if creatinine clearance is less than 30 mL/min) overlapped with warfarin to INR 2.0 to 3.0 for at least 5 days; or dabigatran 150 mg twice daily or edoxaban 60 mg once daily (30 mg if creatinine clearance is 15 to 50 mL/min or weight 60 kg or less) after 5 days of parenteral treatment.
  • Unfractionated heparin 80 units/kg IV bolus then 18 units/kg/h (aPTT 1.5 to 2.5 times control) when thrombolysis or intervention is planned or creatinine clearance is less than 15 to 30 mL/min.
  • Cancer: apixaban 10 mg twice daily for 7 days then 5 mg twice daily, or enoxaparin 1 mg/kg SC twice daily (or 1.5 mg/kg daily) for at least 6 months and while cancer or catheter persists; use caution with direct oral anticoagulants in gastrointestinal and genitourinary cancers because of bleeding.
  • Antiphospholipid syndrome: warfarin to INR 2.0 to 3.0; avoid direct oral anticoagulants.
• Catheter related thrombosis:
  • Keep the catheter if it is working, needed, well positioned and not infected, with anticoagulation for as long as it stays and for at least 3 months in total.
  • Remove the catheter if it is infected, malpositioned, non-functioning, or no longer needed, after starting anticoagulation; no waiting period is needed.
  • Pacemaker or defibrillator lead thrombosis: anticoagulation for 3 months; extract the lead if infected; venoplasty or stenting for symptomatic occlusion.
• Thrombolysis or thrombus removal (symptoms for less than 14 days, severe symptoms with limb threat, superior vena cava involvement, or a young active patient with primary thrombosis, low bleeding risk):
  • Catheter directed alteplase 0.5 to 1 mg/h (maximum total about 20 to 40 mg) through a multi-side-hole catheter, with fibrinogen checked every 4 to 6 hours (stop at less than 1 g/L) and repeat venography at 12 to 24 hours; pharmacomechanical thrombectomy as an alternative.
  • Contraindications: active bleeding, stroke or intracranial surgery within 3 months, major surgery or trauma within 3 weeks, uncontrolled hypertension (greater than 180/110 mmHg), brain metastases.
• Primary thrombosis: after thrombolysis, anticoagulation, then refer for first rib resection with scalenectomy and venolysis within 1 to 3 months, with venoplasty after decompression; place a stent only after decompression.
• Symptom control: arm elevation, early use of the arm, analgesia with paracetamol 1 g four times daily (NSAIDs add bleeding risk on anticoagulation), and a compression sleeve for symptoms (it does not prevent post-thrombotic syndrome).
• Superior vena cava filter: not recommended, except as a last resort when anticoagulation is contraindicated and there is recurrent embolism.
• Special groups:
  • Pregnancy: enoxaparin 1 mg/kg SC twice daily through pregnancy and for at least 6 weeks postpartum (minimum total 3 months); avoid warfarin and direct oral anticoagulants.
  • Intravenous drug users: treat infection, give anticoagulation, and offer opioid agonist therapy (buprenorphine sublingual 2 to 4 mg initially, titrated to 8 to 16 mg daily, or methadone starting at 20 to 30 mg daily with specialist titration).
  • Children and neonates: usually catheter related; weight based enoxaparin (1 mg/kg twice daily, 1.5 mg/kg twice daily in infants), and early catheter removal.
  • Renal impairment and dialysis catheters: unfractionated heparin or warfarin; preserve veins for access.
  • Rifampicin and ritonavir boosted antiretrovirals: avoid direct oral anticoagulants.
• Red flags: chest pain or breathlessness, fever with catheter tenderness, swelling of the face or neck, severe limb pain with cyanosis, bleeding on anticoagulation.
• Follow up: review at 1 to 2 weeks and 3 months; repeat ultrasonography at 3 months to assess resolution; decide anticoagulant duration (stop at 3 months for provoked disease with the catheter removed; continue while the catheter or cancer persists); screen for post-thrombotic syndrome.