Rx of venous thrombosis (DVT/PE) and superficial thrombophlebitis - American College of Chest Physicians guidelines 2012

see also:

• thrombophlebitis
• Mx of lower limb DVT

• risk factors for major bleeding on oral anticoagulants:
  • age > 65yrs
  • age > 75yrs
  • PH bleeding
  • cancer
  • metastatic cancer
  • renal failure
  • liver failure
  • thrombocytopenia
  • previous stroke
  • diabetes
  • anaemia
  • antiplatelet Rx
  • poor anticoagulant control
  • comorbidity and reduced functional capacity
  • recent surgery
  • falls
  • alcohol abuse
• risk of major bleeding in 1st 3 months Rx with oral vitamin K antagonists such as warfarin
  • low risk patient 1.6%
  • intermediate risk patient (2x risk of low risk) 3.2%
  • high risk patient (8 x risk of low risk) 12.8%
• risk of major bleeding on 5yr extended Rx with oral vitamin K antagonists such as warfarin
  • low risk patient 2.4%
  • intermediate risk patient 4.9%
  • high risk patient 19.6%
• risk of death from a major bleed = 11.3% per major bleed
• reduction of recurrent VTE (of which 3.6% will be fatal) over 5yrs Rx with oral vitamin K anatagonists:
  • (based on relative risk reduction: 82%)
  • 1st VTE provoked by surgery: 2.6%
  • 1st VTE provoked by a nonsurgical factor or 1st unprovoked distal DVT: 13.2%
  • 1st unprovoked proximal DVT or PE: 26.4%
  • 2nd unprovoked VTE: 39.6%
• annual risk of recurrent VTE after cessation of anticoagulation:
  • 1st VTE provoked by surgery: 1% 1st yr then 0.5%pa
  • 1st episode of VTE provoked by nonsurgical factor: 5% 1st yr then 2.5% pa
  • 1st episode of unprovoked VTE: 10% 1st yr then 5% pa
  • 2nd episode of unprovoked VTE: 15% 1st yr then 7.5% pa
• post-thrombotic syndrome (PTS)
  • risk factors for higher severity PTS Villalta score at 24 months:
    • mild PTS severity at 1 month (2x risk)
    • moderate PTS severity at 1 month (5x risk)
    • high PTS severity at 1 month (7x risk)
    • thrombosis of common femoral or iliac vein (2.2 higher score compared with distal DVT)
    • higher body mass index (0.14 increase in score per kg/m²)
    • PH ipsilateral venous thrombosis (1.78 increase in score)
    • older age (0.30 increase in score per 10-year age increase)
    • female sex (0.79 increase in score)

• if high clinical suspicion of acute VTE:
  • Rx with parenteral anticoagulants compared with no treatment while awaiting the results of diagnostic tests (Grade 2C).
• if intermediate clinical suspicion of acute VTE:
  • Rx with parenteral anticoagulants compared with no treatment if the results of diagnostic tests are expected to be delayed for more than 4 h (Grade 2C).
• if low clinical suspicion of acute VTE:
  • Rx with parenteral anticoagulants while awaiting the results of diagnostic tests, provided test results are expected within 24 h (Grade 2C).

• ie. DVT of the calf (peroneal, posterior tibial, anterior tibial veins) without involvement of the popliteal or more proximal veins
• when left untreated, ∼15% of symptomatic distal DVT will extend into the proximal veins and that if extension does not occur within 2 weeks, it is unlikely to occur subsequently
• risk factors for extension:
  • positive d-dimer
  • thrombosis that is extensive or close to the proximal veins (eg, > 5 cm in length, involves multiple veins, > 7 mm in maximum diameter)
  • no reversible provoking factor for DVT
  • active cancer
  • history of VTE
  • inpatient status
• recommendations:
  • if no severe symptoms or risk factors for extension:
    • serial imaging of the deep veins for 2 weeks rather than initial anticoagulation (Grade 2C).
    • consider anticoagulation if the thrombus extends but remains confined to the distal veins (Grade 2C).
    • anticoagulation is recommended if the thrombus extends into the proximal veins (Grade 1B).
  • if severe symptoms or risk factors for extension:
    • anticoagulate as per proximal DVT

• anticoagulate if no C/I to anticoagulation
  • do not also insert an IVC filter (Grade 1B)
  • initial Rx with enoxaparin should be 1mg/kg bd or 2mg/kg once daily as 1.5mg/kg once daily appears to be less protective
  • early initiation of VKA such as warfarin (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the INR is 2.0 or above for at least 24 h. Aim for therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) (Grade 1B).
    • provoked by surgery, Rx with anticoagulation for 3 months (Grade 1B regardless of risk of bleeding).
    • provoked by a nonsurgical transient risk factor, Rx with anticoagulation for 3 months (Grade 1B)
    • 1st or subsequent unprovoked DVT of the leg, Rx with anticoagulation for 3 months then evaluate for the risk-benefit ratio of extended therapy:
      • if low-intermediate bleeding risk and proximal DVT then extended anticoagulant therapy(Grade 2B).
      • if high bleeding risk or unprovoked isolated distal DVT of the leg then cease Rx after the 3 months Rx. (Grade 1B).
• if C/I to anticoagulation:
  • insert IVC filter (Grade 1B)
  • plus, commence conventional course of anticoagulant therapy if their risk of bleeding resolves (Grade 2B)
  • however, a permanent IVC filter, of itself, is NOT considered an indication for extended anticoagulation
• early ambulation (eg, without a period of bed rest) when feasible because of its potential to decrease PTS and improve quality of life
  • if oedema and pain are severe, ambulation may need to be deferred. The use of compression therapy is recommended in these patients.
• compression stockings started within 2 weeks of DVT and continued for 2 years appear to reduce PTS by about 50% and do not alter the frequency of recurrent VTE.
  • those with proximal DVT and a previous DVT in the same leg and who have marked symptoms are expected to gain the most benefit from compression stockings.
• patients with acute DVT of the leg and whose home circumstances are adequate, recommend initial treatment at home over treatment in hospital (Grade 1B).
  • conditional on the adequacy of the following home circumstances: well-maintained living conditions, strong support from family or friends, phone access, and ability to quickly return to hospital if there is deterioration. It is also conditional on the patient feeling well enough to be treated at home (eg, does not have severe leg symptoms or comorbidity).

• general advice is Rx as for proximal DVT
• IVC filter recommended only if anticoagulation is C/I as PE may still occur, although risk is lessened, but risk of recurrent DVT and PTS is higher with permanent IVC filters
• patients with the rare complication of impending venous gangrene should be considered for early clot removal, either surgical, or, more preferably, by catheter-directed thrombolysis or perhaps systemic thrombolysis
• patients have extensive thrombosis and are at higher risk of more severe post-thrombotic syndrome (PTS)
• patients without impending venous gangrene who may benefit from early clot removal by thrombolysis must have ALL the following:
  • iliofemoral DVT
  • symptoms for < 14 days
  • good functional status
  • life expectancy of ≥ 1 year
  • low risk of bleeding
• thus some patients may elect to embark on clot removal via either:
  • catheter directed thrombolysis (CDT)
    • evidence is not conclusive of benefit vs risk
    • anticoagulant therapy alone is an acceptable alternative to CDT in all patients with acute DVT who do not have impending venous gangrene
  • systemic thrombolytic therapy:
    • has the potential to reduce PTS at the expense of an increase in major bleeding but evidence is inconclusive and probably favors catheter-directed thrombolysis if the expertise is available
  • surgical thrombectomy and temporary A-V fistula creation
    • generally not as preferable as CDT

• not as benign as once thought - patients with acute SVT of ≥ 5 cm at initial presentation, ∼4% of patients had symptomatic PE, and routine ultrasound detected proximal DVT in 10% and distal DVT in an additional 13% of patients
• patients with SVT above the knee should have ultrasonography to exclude proximal DVT
• The recently published Comparison of ARIXTRA™ in lower LImb Superficial Thrombophlebitis with placebo (CALISTO) study, which compared fondaparinux (2.5 mg/d for 45 days) with placebo in 3,000 patients with SVT (≥ 5 cm in length), has helped to clarify the role of anticoagulants for the treatment of SVT, and the natural history of this condition
  • fondaparinux is very effective at reducing VTE, recurrent SVT, extension of SVT, and the need for venous surgery, and is associated with little bleeding
  • factors that favor the use of anticoagulant therapy in patients with SVT include:
    • extensive SVT;
    • involvement above the knee, particularly if close to the saphenofemoral junction;
    • severe symptoms;
    • involvement of the greater saphenous vein;
    • history of VTE or SVT;
    • active cancer;
    • recent surgery.
• SVT of the lower limb of at least 5 cm in length, suggest the use of a prophylactic dose of fondaparinux or LMWH for 45 days over no anticoagulation (Grade 2B).
  • suggest fondaparinux 2.5 mg daily over a prophylactic dose of LMWH (Grade 2C)

• 75% are “secondary” to CVC, pacemakers, or cancer
• 25% are “primary” - unprovoked with or without thrombophilia, effort-related and thoracic outlet syndrome
• involve the subclavian, axillary, or brachial veins and may include extension to the brachiocephalic vein, superior vena cava, or the internal jugular vein
• may lead to complications, including:
  • symptomatic PE (∼5% of patients)
  • recurrent upper limb DVT (∼8% at 5 years of follow-up)
  • PTS of the arm (∼20% of patients)
• no randomized trials have evaluated treatment of upper limb DVT, recommendations are based on indirect evidence from studies performed in patients with leg DVT, observational studies (generally small), and understanding of the natural history of upper limb DVT.
• in most patients with UEDVT that is associated with a central venous catheter, suggest that the catheter not be removed if it is functional and there is an ongoing need for the catheter (Grade 2C).
• patients with acute UEDVT that involves the axillary or more proximal veins, recommend acute treatment with parenteral anticoagulation (LMWH, fondaparinux, IV UFH, or SC UFH) over no such acute treatment (Grade 1B).
• patients with acute UEDVT that involves the axillary or more proximal veins, suggest LMWH or fondaparinux over IV UFH (Grade 2C) and over SC UFH (Grade 2B).
• patients with acute symptomatic UEDVT, suggest against the use of compression sleeves or venoactive medications (Grade 2C).
• patients who have PTS of the arm, suggest a trial of compression bandages or sleeves to reduce symptoms (Grade 2C).

• UEDVT that involves the axillary or more proximal veins, suggest a minimum duration of anticoagulation of 3 months over a shorter period (Grade 2B).
• patients who have UEDVT that is associated with a central venous catheter that is removed, recommend 3 months of anticoagulation over a longer duration of therapy in patients with no cancer (Grade 1B), and we suggest this in patients with cancer (Grade 2C).
• patients who have UEDVT that is associated with a central venous catheter that is not removed, recommend that anticoagulation is continued as long as the central venous catheter remains over stopping after 3 months of treatment in patients with cancer (Grade 1C), and we suggest this in patients with no cancer (Grade 2C).
• patients who have UEDVT that is not associated with a central venous catheter or with cancer, we recommend 3 months of anticoagulation over a longer duration of therapy (Grade 1B).