Deep vein thrombosis medical therapy

Editors-in-Chief: C. Michael Gibson, M.S., M.D. Associate Editor-In-Chief: Ujjwal Rastogi, MBBS [1]

Deep Vein Thrombosis Microchapters
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Overview

The primary purpose of treatment is to prevent the following:

• Further clot extension,
• Acute Pulmonary embolism,
• Recurrence of thrombosis,
• Prevention of late complications such as:
  • the post-thrombotic syndrome
  • chronic thromboembolic pulmonary hypertension.

Medical Therapy

Anticoagulant therapy is indicated for patients with symptomatic proximal lower extremity DVT, since PE is a fatal complication occurring in half of the untreated patients within few days to weeks.

Five options are available for the initial treatment of DVT:

1. Low-molecular-weight heparin (LMWH) administered subcutaneous (SC), without monitoring.
2. IV unfractionated heparin (UFH), with monitoring.
3. SC UFH, with monitoring
4. Weight-based SC UFH, without monitoring.
5. SC fondaparinux, without monitoring

After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.

Anticoagulation

Main article: Anticoagulation

Anticoagulation is the usual treatment for DVT. In general, patients are initiated on a brief course (less than a week) of low molecular weight heparin, before they are started on a chronic (3 to 6 month) course of warfarin (or related vitamin K inhibitors).

An abnormal D-dimer level at the end of treatment, signals the need for continued treatment, in patients with first unprovoked proximal deep-vein thrombosis.

Thrombolysis

Main article: Thrombolysis

Thrombolysis is generally reserved for extensive clot, e.g. an iliofemoral thrombosis. Although a meta-analysis of randomized controlled trials by the Cochrane Collaboration shows improved outcomes with thrombolysis, there may be an increase in serious bleeding complications.

Direct factor Xa inhibitor

Rivaroxaban (orally active direct factor Xa inhibitor) has been studied in phase III clinical trials for prevention of VTE in hospitalized medically ill patients (MAGELLAN), treatment and secondary prevention of VTE (EINSTEIN). More than 8,000 patients were enrolled in the rivaroxaban clinical development program overall. The study showed that taking rivaroxaban once daily for 35 days was associated with a reduction in the risk of venous thrombosis, compared with standard 10-day treatment with enoxaparin by subcutaneous injection, in acutely ill medical patients. However, bleeding rates were significantly increased with rivaroxaban.

Compression stockings

Elastic compression stockings should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis". The stockings in almost all trials were stronger than routine anti-embolism stockings and created either 20-30 mm Hg or 30-40 mm Hg. Most trials used knee-high stockings. A meta-analysis of randomized controlled trials by the Cochrane Collaboration showed reduced incidence of post-phlebitic syndrome. The number needed to treat is quite potent at 4 to 5 patients need to prevent one case of post-phlebitic syndrome.

ACCP Guidelines (DO NOT EDIT)

ACCP Guidelines- Recommendations for initial approach in patients with acute DVT of the leg (DO NOT EDIT)

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1. In patients with acute DVT of the leg treated with vitamin K antagonist (VKA) therapy, we recommend initial treatment with parenteral anticoagulation (low-molecular-weight heparin [LMWH], fondaparinux, IV unfractionated heparin [UFH], or subcutaneous [SC] UFH) over no such initial treatment (Grade 1B). 2. In patients with a high clinical suspicion of acute VTE, we suggest treatment with parenteral anticoagulants compared with no treatment while awaiting the results of diagnostic tests (Grade 2C). 3. In patients with an intermediate clinical suspicion of acute VTE, we suggest treatment 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). 4. In patients with a low clinical suspicion of acute VTE, we suggest not treating with parenteral anticoagulants while awaiting the results of diagnostic tests, provided test results are expected within 24 h (Grade 2C).

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ACCP Guidelines- Recommendations for initial choice of treatment in patients with acute DVT of the leg (DO NOT EDIT)

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1. In patients with acute DVT of the leg, we recommend early initiation of VKA (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 international normalized ratio (INR) is 2.0 or above for at least 24 h (Grade 1B). 2. In patients with acute DVT of the leg, we suggest LMWH or fondaparinux over IV UFH (Grade 2C) and over SC UFH (Grade 2B for LMWH; Grade 2C for fondaparinux). 3. In patients with acute DVT of the leg treated with LMWH, we suggest once- over twice-daily administration (Grade 2C). 4. In patients with acute DVT of the leg and whose home circumstances are adequate, we recommend initial treatment at home over treatment in hospital (Grade 1B). 5. In patients with acute proximal DVT of the leg, we suggest anti coagulant therapy alone over catheter-directed thrombolysis (CDT) (Grade 2C). 6. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C). 7. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over operative venous thrombectomy (Grade 2C). 8. In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in comparable patients who do not undergo thrombosis removal (Grade 1B). 9. In patients with acute DVT of the leg, we recommend against the use of an inferior vena cava (IVC) filter in addition to anticoagulants (Grade 1B). 10. In patients with acute proximal DVT of the leg and contraindication to anticoagulation, we recommend the use of an IVC filter (Grade 1B). 11. In patients with acute proximal DVT of the leg and an IVC filter inserted as an alternative to anticoagulation, we suggest a conventional course of anticoagulant therapy if their risk of bleeding resolves (Grade 2B). 12. In patients with acute DVT of the leg, we suggest early ambulation over initial bed rest (Grade 2C).

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ACCP Guidelines- Recommendations for use of unfractionated Heparin (DO NOT EDIT)

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1. In patients with acute DVT, if IV UFH is chosen, we recommend that after an initial IV bolus (80 U/kg or 5,000 U), it be administered by continuous infusion (initially at a dose of 18 U/kg/h or 1,300 U/h) with dose adjustment to achieve and maintain an activated partial thromboplastin time (APTT) prolongation that corresponds to plasma heparin levels of 0.3 to 0.7 IU/mL anti-Xa activity by the amidolytic assay rather than administration as IV boluses throughout treatment, or administration without coagulation monitoring (Grade 1C)

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ACCP Guidelines- Recommendations for subcutaneous unfractionated Heparin or intravenous Heparin (DO NOT EDIT)

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1. In patients with acute DVT, if monitored SC UFH is chosen, we recommend an initial dose of 17,500 U, or a weight-adjusted dose of about 250 U/kg bid, with dose adjustment to achieve and maintain an APTT prolongation that corresponds to plasma heparin levels of 0.3 to 0.7 IU/mL anti-Xa activity when measured 6 h after injection rather than starting with a smaller initial dose (Grade 1C). 2. In patients with acute DVT, if fixed-dose, unmonitored SC UFH is chosen, we recommend an initial dose of 333 U/Kg followed by 250 U/kg bid rather than non–weight-based dosing (Grade 1C)

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ACCP Guidelines- Recommendations for use of low molecular weight Heparin (DO NOT EDIT)

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1. In patients with acute DVT, we recommend initial treatment with LMWH SC once or twice daily, as an outpatient if possible (Grade 1C), or as an inpatient if necessary (Grade 1A), rather than treatment with IV UFH. 2. In patients with acute DVT treated with LMWH, we recommend against routine monitoring with anti-factor Xa level measurements (Grade 1A). 3. In patients with acute DVT and severe renal failure, we suggest UFH over LMWH (Grade 2C)

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ACCP Guidelines- Recommendations for duration of anticoagulant therapy (DO NOT EDIT)

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1. In patients with acute VTE who are treated with anticoagulant therapy, we recommend long-term therapy (see section 3.1 for recommended duration of therapy) over stopping anticoagulant therapy after about 1 week of initial therapy (Grade 1B). 2. In patients with a proximal DVT of the leg provoked by surgery, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Grade 1B) , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Grade 1B) , or (iii) extended therapy (Grade 1B regardless of bleeding risk). 3. In patients with a proximal DVT of the leg provoked by a nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Grade 1B) , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Grade 1B), and (iii) extended therapy if there is a high bleeding risk (Grade 1B) . We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (Grade 2B). 4. In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor (see remark), we suggest treatment with anticoagulation for 3 months over treatment of a shorter period (Grade 2C) and recommend treatment with anticoagulation for 3 months over treatment of a longer time-limited period (eg, 6 or 12 months) (Grade 1B) or extended therapy (Grade 1B regardless of bleeding risk). 5. In patients with an unprovoked DVT of the leg (isolated distal [see remark] or proximal), we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration (Grade 1B) . After 3 months of treatment, patients with unprovoked DVT of the leg should be evaluated for the risk-benefit ratio of extended therapy. 6. In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a low or moderate bleeding risk, we suggest extended anticoagulant therapy over 3 months of therapy (Grade 2B). 7. In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a high bleeding risk, we recommend 3 months of anticoagulant therapy over extended therapy (Grade 1B). 8. In patients with a first VTE that is an unprovoked isolated distal DVT of the leg, we suggest 3 months of anticoagulant therapy over extended therapy in those with a low or moderate bleeding risk (Grade 2B) and recommend 3 months of anticoagulant treatment in those with a high bleeding risk (Grade 1B). 9. In patients with a second unprovoked VTE, we recommend extended anticoagulant therapy over 3 months of therapy in those who have a low bleeding risk (Grade 1B), and we suggest extended anticoagulant therapy in those with a moderate bleeding risk (Grade 2B). 10. In patients with a second unprovoked VTE who have a high bleeding risk, we suggest 3 months of anticoagulant therapy over extended therapy (Grade 2B). 11. In patients with DVT of the leg and active cancer, if the risk of bleeding is not high, we recommend extended anticoagulant therapy over 3 months of therapy (Grade 1B), and if there is a high bleeding risk, we suggest extended anticoagulant therapy (Grade 2B). 12. In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).

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ACCP Guidelines- Recommendations for intensity of anticoagulant effect (DO NOT EDIT)

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1. In patients with DVT of the leg who are treated with VKA, we recommend a therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) over a lower (INR <2) or higher (INR 3.0-5.0) range for all treatment durations (Grade 1B).

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ACCP Guidelines- Recommendations for treatment of isolated distal DVT (DO NOT EDIT)

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1. In patients with acute isolated distal DVT of the leg and without severe symptoms or risk factors for extension, we suggest serial imaging of the deep veins for 2 weeks over initial anticoagulation (Grade 2C). 2. In patients with acute isolated distal DVT of the leg and severe symptoms or risk factors for extension (see text), we suggest initial anticoagulation over serial imaging of the deep veins (Grade 2C). 3. In patients with acute isolated distal DVT of the leg who are managed with initial anticoagulation, we recommend using the same approach as for patients with acute proximal DVT (Grade 1B). 4. In patients with acute isolated distal DVT of the leg who are managed with serial imaging, we recommend no anticoagulation if the thrombus does not extend (Grade 1B) ; we suggest anticoagulation if the thrombus extends but remains confined to the distal veins (Grade 2C) ; we recommend anticoagulation if the thrombus extends into the proximal veins (Grade 1B).

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ACCP Guidelines- Recommendations for treatment of asymptomatic DVT of the leg (DO NOT EDIT)

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1. In patients who are incidentally found to have asymptomatic DVT of the leg, we suggest the same initial and long-term anticoagulation as for comparable patients with symptomatic DVT (Grade 2B).

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AHA Guidelines (DO NOT EDIT)

AHA Guidelines for duration of anticoagulant therapy

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1. Adult patients with IFDVT who receive oral warfarin as first-line long-term anticoagulation therapy should have warfarin overlapped with initial anticoagulation therapy for a minimum of 5 days and until the INR is ≥2.0 for at least 24 hours, and then targeted to an INR of 2.0 to 3.0 (Class I; Level of Evidence A). 2. Patients with first-episode IFDVT related to a major reversible risk factor should have anticoagulation stopped after 3 months (Class I; Level of Evidence A). 3. Patients with recurrent or unprovoked IFDVT should have at least 6 months of anticoagulation and be considered for indefinite anticoagulation with periodic reassessment of the risks and benefits of continued anticoagulation (Class I; Level of Evidence A). 4. Cancer patients with IFDVT should receive LMWH monotherapy for at least 3 to 6 months, or as long as the cancer or its treatment (eg, chemotherapy) is ongoing (Class I; Level of Evidence A). 5. In children with DVT, the use of LMWH monotherapy may be reasonable (Class IIb; Level of Evidence C).

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Guidelines Resources

• Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

• Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension (A Scientific Statement From the American Heart Association).