Treatment of deep vein thrombosis and pulmonary embolism
- Prevention of thrombus growth
- Symptomatic relief
- Prevention of DVT and PE recurrence
Treatment of DVT and PE with anticoagulants
|ACCP recommendation||Grade of recommendation|
aNo Grade of recommendation available for rivaroxaban or dabigatran.
ACCP, American College of Chest Physicians; DVT, deep vein thrombosis; LMWH, low molecular weight heparin; PE, pulmonary embolism; UFH, unfractionated heparin; VKA, vitamin K antagonist.
|Acute DVT or PE||Parenteral anticoagulation (overlapping with a VKA) or rivaroxaban||1Ba|
|LMWH or fondaparinux suggested over:|
|PE with hypotension||Thrombolytic therapy (for patients who do not have high risk of bleeding)||2C|
|DVT or PE without cancer||VKA suggested over LMWH||2C|
|LMWH suggested over dabigatran or rivaroxaban||2Ca|
|DVT or PE with cancer||LMWH suggested over VKA||2B|
|VKA suggested over dabigatran or rivaroxaban||2Ba|
|Duration of anticoagulant therapy|
|Proximal DVT or PE||3 months recommended over shorter duration||1B|
|First proximal DVT or PE provoked by surgery or a non-surgical transient risk factor||3 months||1B (2B if provoked by a nonsurgical risk factor and a low/moderate risk of bleeding)|
|Unprovoked DVT or PE||Extended therapy if risk of bleeding is low/moderate||2B|
|3 months if risk of bleeding is high||1B|
|DVT or PE associated with active cancer||Extended therapy recommended over 3 months therapy||1B (2B if risk of bleeding is high)|
Approved anticoagulants for treatment of DVT and PE
|AT, antithrombin; bid, twice daily; CI, confidence interval; DVT, deep vein thrombosis; INR, international normalized ratio; LMWH, low molecular weight heparin; od, once daily; PE, pulmonary embolism; s.c., subcutaneous; UFH, unfractionated heparin; VKA, vitamin K antagonist.|
|UFH||Factor Xa and thrombin (indirect via AT)||Weight-adjusted s.c. bolus dose followed by i.v. infusion; overlapping with a VKA for at least 5 days and until INR >2.0 for 2 consecutive days|
|LMWH||Factor Xa and thrombin (indirect via AT)||Weight-adjusted s.c. regimen; overlapping with a VKA for at least 5 days and until INR >2.0 for 2 consecutive days||COLUMBUS358|
|Fondaparinux||Factor Xa (indirect via AT)||Weight-adjusted s.c. regimen (standard dose 7.5 mg) od; overlapping with a VKA for at least 5 days and until INR >2.0 for 2 consecutive days359||MATISSE DVT359
|VKA||Vitamin K (inhibits synthesis of Factors II, VII, IX and X)||Oral, commenced in parallel with initial parenteral agent, which is then discontinued once INR is in the range 2.0–3.0352
For warfarin, typical induction 5 mg (for older, frailer patients) or 10 mg (for younger, healthier patients) od for 2 days, followed by adjusted-doses to maintain a target INR of 2.5 (range, 2.0–3.0)
Treatment continues for 3–12 months depending on risk factors, or longer if risk factors for recurrence persist
|Cochrane Database Systematic Review361|
|Rivaroxaban (Treatment of DVT and prevention of recurrent VTE only||Factor Xa (direct)||Oral, 15 mg bid for 3 weeks then 20 mg od Oral 15 mg bid for 3 weeks then 15 mg od for patients with moderate (CrCl 30–49 ml/min) or severe (CrCl 15–29 ml/min) renal impairment.319 A reduction of the dose from 20 mg od to 15 mg od should be considered if the patient’s assessed risk of bleeding outweighs the risk of recurrent DVT and PE||EINSTEIN DVT362
Other treatment approaches for DVT and PE
- 20 - Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med. 2004;351(3):268-277.
- 337 - Kearon C, Akl EA, Comerota AJ et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis: American College of Chest Physicians evidence-based clinical practice guidelines (9th Edition). Chest 2012;141:e419S–e494S.
- 319 - Bayer Pharma AG. Xarelto® (rivaroxaban) Summary of Product Characteristics. 2012. Available at: [accessed 21 September 2012].
- 358 - The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997;337:657–662.
- 359 - Büller HR, Davidson BL, Decousus H et al. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med 2004;140:867–873.
- 360 - The Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003;349:1695–1702.
- 352 - Torbicki A, Perrier A, Konstantinides S et al. 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 2008;29:2276–2315.
- 361 - Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev 2006:CD001367.
- 362 - The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499–2510.
- 363 - The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287–1297.
- 364 - Almoosa K. Is thrombolytic therapy effective for pulmonary embolism? Am Fam Physician 2002;65:1097–1102.
- 8 - Tapson VF. Acute pulmonary embolism. N Engl J Med. 2008;358(10):1037-1052.
- Venous thromboembolism
- A condition in which a blood clot (thrombus) forms in a vein, which in some cases then breaks free and enters the circulation as an embolus, finally lodging in and completely obstructing a blood vessel, e.g., in lungs causing a PE. The term encompasses both DVT and PE.
- The use of medication or medical devices to prevent the formation of blood clots.
- Not through the alimentary canal but rather by injection through another route.
- Vitamin K
- An essential cofactor in the carboxylation of glutamic residues on the procoagulant forms of Factors II, VII, IX, and X. This ultimately leads to increased formation of thrombin and fibrin.
- A vitamin K antagonist. Most commonly used oral anticoagulant in chronic prevention or treatment of VTE.
- Coagulation monitoring
- Coagulation monitoring is practice of checking a specific coagulation parameter in order to adjust the dose. A precise adjustment of the drug intake allows the patient to stay within a defined therapeutic range, which is measured by prothrombin time or International Normalized Ratio (INR).
- Factor Xa
- The activated form of Factor X. It catalyses the conversion of prothrombin to thrombin in conjunction with other cofactors.
- An anticoagulant that exerts its activity by binding to antithrombin and greatly increasing its activity. The principal coagulation factors inhibited by heparin are Factors IIa and Xa. It is administered by intravenous or subcutaneous injection.
- Oral, direct Factor Xa inhibitor.
- Vitamin K antagonists
- Vitamin K antagonists block the regeneration of the reduced form of vitamin K.