Acute Deep Venous Thrombosis (DVT) of the Leg:
Initial Anticoagulant Therapy
from the ACCP Guidelines, 9th Ed.
The ACCP‘s 9th edition of their clinical practice guidelines for prevention and treatment of venous thromboembolism (VTE) were published in February 2012, and we’re summarizing the 801-page long document piece by piece. (See also the other sections of the 9th edition ACCP recommendations.)
Here we review the section on the initial treatment of acute deep venous thrombosis (DVT) of the leg with antithrombotic / anticoagulant therapy.
DVT ≠ PE: Overlapping Diseases with Subtle Differences
Although deep venous thrombosis precedes and often coexists with pulmonary embolism, and both are treated with anticoagulation, the two conditions are not interchangeable. Still, they have historically been considered so, for some good reasons:
- Most people with symptomatic DVT also have PE (either symptomatic or “silent”).
- Most people with symptomatic PE also have DVT (with or without symptoms).
- Clinical trials “lumping” patients with DVT alone, DVT and PE, or PE alone have had similar outcomes for efficacy and safety of anticoagulation treatment.
- The risk of pulmonary embolism after proximal DVT (but not distal) and after a first PE appear to be similar.
However, there are some subtle but critically important differences between the two conditions:
- The risk of death within one month is far higher in people presenting with PE, compared to DVT.
- Recurrence after a PE is more likely to be a PE than a DVT (i.e., more dangerous). In patients with a PE, about 60% of recurrent events are PEs, while in patients with an initial DVT (without PE), only 20% of recurrent events will be PEs.
These increased risks tend to justify a more aggressive treatment approach for patients who present with PE (longer or more intense anticoagulation, IVC filters, etc.), compared to isolated DVT.
People with Proximal Leg DVT Should Initially Receive 5+ Days Heparin or Fondaparinux (and Warfarin)
- Patients with acute proximal leg DVT who will receive warfarin should initially be treated with heparin (low molecular weight or unfractionated, subcutaneous or intravenous) or fondaparinux (Grade 1B)*. Two randomized trials showed the benefit of this approach over no heparin.
- Heparin or fondaparinux (parenteral anticoagulation) should be started the same day as warfarin, and continued for at least 5 days and until the INR is 2.0 or greater for 24 hours (Grade 1B). If the INR becomes supratherapeutic (>3.0) before 5 days, the heparin/fondaparinux should be stopped.
* This and all the ACCP’s recommendations assume patients have not had recent surgery or other major risk factors for bleeding. Clinical judgment must always take precedence over guidelines.
- In patients at high clinical suspicion for DVT, ACCP suggests treating immediately pending test results; at intermediate suspicion, waiting up to 4 hours for test results before treating; and at low suspicion, waiting up to 24 hours for test results before treating (Grade 2C).
Isolated Distal Leg DVTs: Many Do Not Merit Diagnosis or Treatment
Distal (calf) DVTs involve the peroneal, anterior tibial, or posterior tibial vein, without involving the popliteal vein or more proximal veins. Most will never extend proximally or embolize, and anticoagulation is therefore unnecessary and potentially harmful in these cases. However, about 15% of untreated distal DVTs will extend proximally, and some will then result in PE. Therefore, the ideal approach to diagnosis and management of distal DVTs is unclear.
In a large majority of patients with distal DVTs, proximal extension will occur within 2 weeks. The ACCP authors seem concerned about overdiagnosis of harmless distal DVT using whole-leg ultrasound, resulting in unnecessary anticoagulation and avoidable bleeding. They seems to favor the preferential use of proximal-leg vein ultrasound, rather than whole-leg ultrasound, for this reason. (See also the ACCP Diagnosis of DVT guidelines.)
- For non-hospitalized patients with acute isolated distal leg DVT who do not have severe symptoms or risk factors for proximal extension*, ACCP suggests repeating the leg ultrasound at 1 and 2 weeks or sooner (Grade 2C).
- If there are severe symptoms or risk factors for extension in a patient with isolated acute distal DVT, ACCP recommends treating with initial anticoagulation (Grade 2C).
* Risk factors for proximal extension of distal leg DVT are believed to include active cancer, previous VTE, no reversible provoking factor for DVT, hospitalized status, a DVT close to the proximal veins, > 5 cm long, involving multiple veins, or > 7 mm in maximum diameter.
Low-Molecular Weight Heparin or Fondaparinux Are Preferred for DVT Treatment
- ACCP suggests low-molecular weight heparin or fondaparinux, rather than unfractionated heparin, as first-line treatment for acute DVT (Grade 2B/2C). Enoxaparin, dalteparin, and tinzaparin are the low molecular weight heparins available in the U.S.; however, only enoxaparin and tinzaparin have FDA indications for the treatment of acute DVT or PE (at this writing).
- ACCP suggests daily rather than twice-daily administration of LMWH (Grade 2C). In the U.S., this is a tacit endorsement of tinzaparin, because studies suggest enoxaparin may not be effective in treating DVT in a single dose of 1.5 mg/kg, and 2.0 mg/kg once daily is not approved or recommended. Enoxaparin is available in generic form; tinzaparin is not.
Patients with Acute DVT May Be Treated at Home
Six studies have strongly suggested the safety and efficacy of home treatment for acute DVT of the leg; however, they are less than definitive because most did not randomize patients to home vs. inpatient treatment. All economic studies have concluded that home treatment provides cost savings.
- ACCP recommends initial treatment of acute DVT of the leg at home, when home circumstances are favorable (including good social support, telephone access, and ability to return to the hospital rapidly if necessary). (Grade 1B)
Patients With Acute Leg DVT May Get Out of Bed and Walk
Evidence supporting early ambulation in people with acute DVT of the leg is imprecise and of low quality overall. However, trials weakly suggested the risk of bed rest was worse than the risk of precipitating PE by walking with a leg DVT.
- ACCP suggests people with acute DVT do not need a period of bed rest, and should walk as soon as feasible to reduce the risk of post-thrombotic syndrome (Grade 2C).
Kearon C et al. Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guideline. Chest 2012; 141 (2_suppl): e419-e494S.