Deep vein thrombosis medical therapy
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Resident Survival Guide |
Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] ; Kashish Goel, M.D.; Assistant Editor(s)-In-Chief: Justine Cadet
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Deep Vein Thrombosis Microchapters |
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Diagnosis |
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Treatment |
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Special Scenario |
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Trials |
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Case Studies |
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Deep vein thrombosis medical therapy On the Web |
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Risk calculators and risk factors for Deep vein thrombosis medical therapy |
For the algorithms about the treatment choices, click here.
Overview
Anticoagulation therapy is the mainstay of the treatment of deep vein thrombosis (DVT). The medical treatment of DVT consists of an initial parenteral anticoagulation therapy and a long term anticoagulation therapy. The primary purpose of treatment is to prevent further clot extension, acute pulmonary embolism, recurrence of thrombosis, and late complications such as post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension. The treatment of DVT with parental anticoagulation should be initiated in case of intermediate or high suspicion of suspected DVT even before the diagnostic confirmatory tests are complete. The choice of parental anticoagulation include: low molecular weight heparin (LMWH), fondaparinux, IV unfractionated heparin (UFH) and SC-UFH; however, the administration of LMWH (once daily rather than twice) and fondaparinux is recommended over IV-UFH and SCUFH. Parental anticoagulation therapy should be administered for at least 5 days and until the INR is equal or more than 2 for more than 24 hours. Patients who receive long term therapy with anticoagulation should be assessed regularly for the risks vs benefits of anticoagulation therapy.[1] An abnormal D-dimer level at the end of treatment may signal the need for continued treatment in patients with their first unprovoked proximal deep-vein thrombosis.[2]
Parenteral Anticoagulation Therapy
Heparin
- Heparin binds to the enzyme inhibitor antithrombin III (AT). The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa.
- The side effects of heparin include bleeding, heparin-induced thrombocytopenia and osteoporosis.[3] In patients with suspected or confirmed heparin-induced thrombocytopenia, lepirudin or argatroban should be used.
- The anticoagulant effects of heparin can be reversed with IV protamine sulfate.[3]
Heparin Dosage
Shown below is a table depicting the dosage of heparin for the treatment of DVT. Note that the dose of heparin used in the treatment of acute coronary syndrome is lower than that used for the treatment of PE.[3]
| Mode of administration of Heparin | Dosage |
| IV injection | 80 U/kg as bolus, followed by 18 U/kg/h, OR 70 U/kg as bolus, followed by 15 U/kg/h for stroke or cardiac patients[4] |
| SC injection | 333 U/kg as bolus, followed by 250 U/kg[4] |
Adjustment of Heparin Dosage According to aPTT
aPTT should be monitored during treatment with Heparin. Prolongation of apTT correlates with an elevated serum concentration of heparin and requires adjustment of the dosage. Shown below is a table depicting the variation in the dosage according the aPTT.
| aPTT | Variation in the dosage[5] |
| < 1.2 x control (<35 s) | Bolus: 80 U/kg Infusion rate: increase by 4 U/kg/h |
| 1.2-1.5 x control (35-45 s) | Bolus: 40 U/kg Infusion rate: increase by 2 U/kg/h |
| 1.5-2.3 x control (46-70 s) | Continue the same dosage |
| 2.3-3.0 x control (71-90 s) | Infusion rate: decrease by 2 U/kg/h |
| > 3.0 x control (>90s) | Stop infusion for a period of 1 hour, then Infusion rate: decrease by 3 U/kg/h |
Platelet Monitoring
Among patients started on heparin, if the risk of heparin induced thrombocytopenia is more than 1%, monitor platelet count every 2 to 3 days from the 4th until the 14th day of treatment or until the discontinuation of heparin.[1]
Low Molecular Weight Heparin
- LMWH is used as a first line therapy for the initial anticoagulation therapy for PE among patients with non-high risk PE.[3]
- In addition, LMWH can also be used for the long term anticoagulation treatment for PE, but vitamin K antagonist are recommended as first line therapy. However, among cancer patients with provoked PE, LMWH is the first line therapy for the long term anticoagulation treatment.[3] LMWH is preferred in pregnancy to avoid the known teratogenic effects of warfarin.
- LMWH is administered subcutaneously and does not require routine coagulation monitoring.
- The recommended doses for treatment of PE are:[3]
- Enoxaparin : 1 mg/Kg body weight (twice daily) OR 1.5 mg/kg once daily
- Tinzaparin : 175 U/Kg body weight (once daily)
Fondaparinux
- Fondaparinux is used as a first line therapy for the initial anticoagulation therapy for PE among patients with non-high risk PE. The antithrombotic activity of fondaparinux sodium is the result of antithrombin III (ATIII)-mediated selective inhibition of factor Xa. Fondaparinux does not require routine coagulation monitoring.
- Recommended doses for the treatment of PE depend on the weight of the patient:
- Weight <50 Kg: 5 mg (once daily)
- Weight between 50 Kg to 100 Kg: 7.5 mg (once daily)
- Weight >100 Kg: 10 mg (once daily)
Oral Anticoagulation Therapy
Vitamin K Antagonist
- Vitamin K antagonist is the first line therapy for long term anticoagulation treatment of pulmonary embolism, with the exception of patients with cancer among whom LMWH is preferred over warfarin.[1]
- Warfarin should be started as soon as possible following the initiation of parenteral anticoagulation therapy, preferably at the same day. Parenteral anticoagulation therapy should be continued for at least 5 days concomitantly with warfarin until INR reaches 2.[1]
- Warfarin is administered as follows:
- NSAIDs, COX2 selective NSAIDs and some antibiotics should be avoided when warfarin is administered.[4]
Factor X Inhibitors
Rivaroxaban is an oral factor X inhibitors that can be used in the long term treatment of PE.
Direct Thrombin Inhibitors
Dabigatran is an oral direct thrombin inhibitors that can be used in the long term treatment of PE.
Thrombolysis
Catheter-Directed Thrombolysis
- Catheter-Directed Thrombolysis for acute DVT has been evaluated in small randomized trials and have shown that it may preserve venous valve function, reduce post-thrombotic syndrome and improve quality of life. However, evidence regarding mortality, recurrent VTE and major bleeding is lacking.
- According to ACCP guidelines[1], catheter-directed thrombolysis should be considered only in patients who meet all of the following criteria:
- Iliofemoral DVT
- Symptoms < 14 days
- Good functional status
- Life expectancy ≥1 year
- Low risk of bleeding
ACCP Recommendations[1]
| “ |
1. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C). 2. In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal. |
” |
Systemic Thrombolysis
- A Cochrane meta-analysis of randomized controlled trials showed reduced incidence of post-thrombotic syndrome and increased the vein patency, but it was associated with increased risk of bleeding.[6]
- Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
- Further, ACCP[1] recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.
- Major Contraindications
- Structural intracranial disease
- Previous intracranial hemorrhage
- Ischemic stroke within 3 mo
- Active bleeding
- Recent brain or spinal surgery
- Recent head trauma with fracture or brain injury
- Bleeding diathesis
- Relative Contraindications
- Systolic BP >180 mm Hg
- Diastolic BP >110 mm Hg
- Recent bleeding (nonintracranial)
- Recent surgery
- Recent invasive procedure
- Ischemic stroke more that 3 mo previously
- Anticoagulation (eg, VKA therapy)
- Traumatic cardiopulmonary resuscitation
- Pericarditis or pericardial fl uid
- Diabetic retinopathy
- Pregnancy
- Age >75 y
- Low body weight (eg, <60 kg)
- Female sex
- Black race
ACCP Recommendations[1]:
| “ |
1. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C). 2. In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal. |
” |
Compression Stockings
Three randomized control trial conducted in Europe[7] [8]have found, that after the diagnosis of first-episode of proximal DVT, the daily use of knee-high graduated compression stockings (ECS) for 2 years is associated with marked reductions in the frequency of Post-thrombotic syndrome (PTS).
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".[7] The stockings in almost all trials were stronger than routine anti-embolism stockings and were used with 20-30 mm Hg or 30-40 mm Hg pressure gradient. Most trials used knee-high stockings. A cochrane meta-analysis of randomized controlled trials reported a reduced incidence of post-phlebitic syndrome.[9] The number needed to treat, that is, to prevent one case of post-thrombotic syndrome was 4 to 5 patients.[10]
2012 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis (DO NOT EDIT)[1]
Recommendations for Initial Choice of Treatment in Patients with Acute DVT of the Leg (DO NOT EDIT)[11]
| Grade 1 |
| "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 (Level of evidence B)" |
| "2. In patients with acute DVT of the leg and whose home circumstances are adequate, we recommend initial treatment at home over treatment in hospital (Level of evidence B)." |
| "3. 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 (Level of evidence B)." |
| "4. In patients with acute DVT of the leg, we recommend against the use of an inferior vena cava (IVC) filter in addition to anticoagulants (Level of evidence B)." |
| "5. In patients with acute proximal DVT of the leg and contraindication to anticoagulation, we recommend the use of an IVC filter (Level of evidence B)." |
| Grade 2 |
| "1. In patients with acute DVT of the leg, we suggest LMWH or fondaparinux over IV UFH (Level of evidence C) and over SC UFH (Level of evidence B) for LMWH;(Level of evidence C) for fondaparinux)." |
| "2. In patients with acute DVT of the leg treated with LMWH, we suggest once- over twice-daily administration (Level of evidence C)." |
| "3. In patients with acute proximal DVT of the leg, we suggest anti coagulant therapy alone over catheter-directed thrombolysis (CDT) (Level of evidence C)." |
| "4. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Level of evidence C)." |
| "5. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over operative venous thrombectomy (Level of evidence C)." |
| "6. 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 (Level of evidence B)." |
| "7. In patients with acute DVT of the leg, we suggest early ambulation over initial bed rest (Level of evidence C)." |
ACCP 2012 Guidelines: Recommendations for Duration of Anticoagulant Therapy (DO NOT EDIT)[11]
| Grade 1 |
| "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 (Level of evidence B)" |
| "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 (Level of evidence B)" , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Level of evidence B) , or (iii) extended therapy (Level of evidence B 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 (Level of evidence B) , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Level of evidence B), and (iii) extended therapy if there is a high bleeding risk (Level of evidence B) ." |
| "4. In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor , we recommend treatment with anticoagulation for 3 months over treatment of a longer time-limited period (eg, 6 or 12 months) (Level of evidence B) or extended therapy (Level of evidence B) 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 (Level of evidence B) . 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 high bleeding risk, we recommend 3 months of anticoagulant therapy over extended therapy (Level of evidence B). " |
| "7. In patients with a first VTE that is an unprovoked isolated distal DVT of the leg, we recommend 3 months of anticoagulant treatment in those with a high bleeding risk (Level of evidence B)." |
| "8. 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 (Level of evidence B)". |
| "9. In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually)." |
| "10. 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 (Level of evidence B)". |
| Grade 2 |
| "1. In patients with DVT of the leg and active cancer, if there is a high bleeding risk, we suggest extended anticoagulant therapy (Level of evidence B)." |
| "2. 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 (Level of evidence B)." |
| "3. In patients with a second unprovoked VTE who have a high bleeding risk, we suggest 3 months of anticoagulant therapy over extended therapy (Level of evidence B)." |
| "4. In patients with a proximal DVT of the leg provoked by a nonsurgical transient risk factor,We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (Level of evidence B)." |
| "5.In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor , we suggest treatment with anticoagulation for 3 months over treatment of a shorter period (Level of evidence C). " |
| "6. 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 (Level of evidence B)." |
| "7. In patients with a second unprovoked VTE, we suggest extended anticoagulant therapy in those with a moderate bleeding risk (Level of evidence B). " |
AHA 2011 Guidelines for Duration of Anticoagulant Therapy (DO NOT EDIT)[12]
| Class I |
| "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 (Level of Evidence: A) " |
| "2. Patients with first-episode IFDVT related to a major reversible risk factor should have anticoagulation stopped after 3 months (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 (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 (Level of Evidence: A). " |
| Class IIb |
| "1. In children with DVT, the use of LMWH monotherapy may be reasonable (Level of Evidence: C). " |
ACCP 2012 Guidelines: Recommendations for Intensity of Anticoagulant Effect (DO NOT EDIT)[11]
| Grade 1 |
| "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 (Level of evidence B)". |
ACCP 2012 Guidelines: Recommendations for Treatment of Isolated Distal DVT (DO NOT EDIT)[11]
| Grade 1 |
| "1. 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 (Level of evidence B). " |
| "2. 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 (Level of evidence B) ; we recommend anticoagulation if the thrombus extends into the proximal veins (Level of evidence B). " |
| Grade 2 |
| "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 (Level of evidence C)." |
| "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 (Level of evidence C)." |
| "3. In patients with acute isolated distal DVT of the leg who are managed with serial imaging, we suggest anticoagulation if the thrombus extends but remains confined to the distal veins (Level of evidence C)." |
ACCP 2012 Guidelines: Recommendations for Treatment of Asymptomatic DVT of the Leg (DO NOT EDIT)[11]
| Grade 2 |
| "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 (Level of evidence B)". |
ACCP 2012 Guidelines: Recommendations for Treatment in Special Situations (DO NOT EDIT)[11]
| Grade 2 |
| "1. In patients with DVT of the leg and no cancer, we suggest VKA therapy over LMWH for long-term therapy (Level of evidence C) . For patients with DVT and no cancer who are not treated with VKA therapy, we suggest LMWH over dabigatran or rivaroxaban for long-term therapy (Level of evidence C)". |
| "2. In patients with DVT of the leg and cancer, we suggest LMWH over VKA therapy (Level of evidence B). In patients with DVT and cancer who are not treated with LMWH, we suggest VKA over dabigatran or rivaroxaban for long-term therapy (Level of evidence B). |
| "3. In patients with DVT of the leg who receive extended therapy, we suggest treatment with the same anticoagulant chosen for the first 3 months (Level of evidence C). |
ACCP 2012 Guidelines: Recommendations for Post-Thrombotic Syndrome (DO NOT EDIT)[11]
| Grade 2 |
| "1. In patients with acute symptomatic DVT of the leg, we suggest the use of compression stockings (Level of evidence B). " |
| "2. In patients with PTS of the leg, we suggest a trial of compression stockings (Level of evidence C). " |
| "3. In patients with severe PTS of the leg that is not adequately relieved by compression stockings, we suggest a trial of an intermittent compression device (Level of evidence B). " |
| "4. In patients with PTS of the leg, we suggest that venoactive medications (eg, rutosides, defibrotide, and hidrosmin) not be used (Level of evidence C). " |
ACC/AHA 2011 Guidelines- Recommendations for Initial Anticoagulation for Patients With IFDVT (DO NOT EDIT)[12]
| Class I |
| "1. In the absence of suspected or proven heparin-induced thrombocytopenia, patients with IFDVT should receive therapeutic anticoagulation with either intravenous UFH (Level of Evidence: A), UFH by subcutaneous injection (Level of Evidence: B), an LMWH (Level of Evidence: A), or fondaparinux (Level of Evidence: A)." |
| "2. Patients with IFDVT who have suspected or proven heparin-induced thrombocytopenia should receive a direct thrombin inhibitor (Level of Evidence: B)" |
ACC/AHA 2011 Guidelines- Recommendations for Long-Term Anticoagulation Therapy for Patients With IFDVT (DO NOT EDIT)[12]
| Class I |
| "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 (Level of Evidence: A)." |
| "2. Patients with first-episode IFDVT related to a major reversible risk factor should have anticoagulation stopped after 3 months (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 (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 (Level of Evidence: A)" |
| Class IIa |
| "1. In children with DVT, the use of LMWH monotherapy may be reasonable (Level of Evidence: C)" |
ACC/AHA 2011 Guidelines- Recommendations for Use of Compression Therapy (DO NOT EDIT)[12]
| Class I |
| "1. Patients with iliofemoral DVT should wear 30– to 40–mm Hg knee-high graduated ECS on a daily basis for at least 2 years (Level of Evidence: B)." |
| Class IIa |
| "1. In patients with prior iliofemoral DVT and symptomatic PTS, daily use of 30– to 40–mm Hg knee-high graduated ECS is reasonable (Level of Evidence: C)." |
| Class IIb |
| 1. In patients with prior iliofemoral DVT and severe edema, intermittent sequential pneumatic compression followed by daily use of 30– to 40–mm Hg knee-high graduated ECS may be considered (Level of Evidence: B). |
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 {{http://www.wikidoc.org//index.php/Template:Cite_journal{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ et al.| title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268 }}
- ↑ Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A; et al. (2006). "D-dimer testing to determine the duration of anticoagulation therapy". N Engl J Med. 355 (17): 1780–9. doi:10.1056/NEJMoa054444. PMID 17065639. Review in: Evid Based Med. 2007 Apr;12(2):45 Review in: ACP J Club. 2007 Mar-Apr;146(2):29
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Garcia DA, Baglin TP, Weitz JI, Samama MM (2012). "Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e24S–43S. doi:10.1378/chest.11-2291. PMID 22315264. Unknown parameter
|month=ignored (help) - ↑ 4.0 4.1 4.2 Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ; et al. (2012). "Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e152S–84S. doi:10.1378/chest.11-2295. PMC 3278055. PMID 22315259.
- ↑ Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P; et al. (2008). "Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)". Eur Heart J. 29 (18): 2276–315. doi:10.1093/eurheartj/ehn310. PMID 18757870.
- ↑ Watson L, Armon M. "Thrombolysis for acute deep vein thrombosis". Cochrane Database Syst Rev: CD002783. PMID 15495034.
- ↑ 7.0 7.1 Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E; et al. (2004). "Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial". Ann Intern Med. 141 (4): 249–56. PMID 15313740. Review in: ACP J Club. 2005 Jan-Feb;142(1):7
- ↑ Partsch H, Kaulich M, Mayer W (2004). "Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome". Int Angiol. 23 (3): 206–12. PMID 15765034.
- ↑ Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M. "Non-pharmaceutical measures for prevention of post-thrombotic syndrome". Cochrane Database Syst Rev: CD004174. doi:10.1002/14651858.CD004174.pub2. PMID 14974060.
- ↑ Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G (2006). "Review on the value of graduated elastic compression stockings after deep vein thrombosis". Thromb Haemost. 96 (4): 441–5. PMID 17003920.
- ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ (2012). "Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): 7S–47S. doi:10.1378/chest.1412S3. PMID 22315257. Unknown parameter
|month=ignored (help) - ↑ 12.0 12.1 12.2 12.3 Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK (2011). "Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association". Circulation. 123 (16): 1788–830. doi:10.1161/CIR.0b013e318214914f. PMID 21422387. Retrieved 2012-02-11. Unknown parameter
|month=ignored (help)