Pulmonary embolism medical therapy
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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]
Overview
In most cases, anticoagulant therapy is the mainstay of treatment. For details, visit treatment approach. This chapter discusses the recommended doses.
Treatment Protocol[1]
Stabilize the patient
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Initial Treatment options (≤5 Days)
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| Long term treatment (≥3 Month) (INR target, 2.0-3.0) | |||||||||||||||||||
| Extended treatment (Indefinite) (INR target, 2.0-3.0 OR 1.5-1.9) | |||||||||||||||||||
Parenteral Anticoagulants[2]
Heparin
- Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
- Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
- The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
- Efficacy of heparin in the initial treatment of DVT or PE is highly dependent on dosage.
- Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
- If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
- The dose for acute coronary syndrome is lower as compared to the treatment of DVT
- The main side effects are heparin-induce thrombocytopenia and osteoporosis.
- One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.
Low molecular weight heparin
- LMWH is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
- The recommended doses for treatment of PE/DVT are:
- Enoxaparin : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for VTE prophylaxis.
- Tinzaparin : 175 U/Kg body weight (once daily).
- The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of Enoxaparin should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.
Factor Xa Inhibitors[2]
- Fondaparinux binds to antithrombin and inhibits factor Xa.
- A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
- Recommended dosages for treatment of DVT or PE are:
- Patient weighing <50 Kg (110 lb): 5 mg (once daily).
- Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
- Patient weighing >100 Kg (220 lb): 10 mg (once daily).
Direct thrombin inhibitors
- Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.
Hirudin
- The recommended dose of IV lepirudin for heparin induced thrombocytopenia is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.
- The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
- When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.
Bivalirudin
- Recommended dose of Bivalirudin is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
- Dose reduction should be considered in patients with moderate to severe renal impairment.
Argatroban
- Argatroban is used for the treatment and prevention of heparin-induced thrombocytopenia associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of heparin-induced thrombocytopenia.
- Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.
Warfarin
References
- ↑ Agnelli G, Becattini C (2010). "Acute pulmonary embolism". N Engl J Med. 363 (3): 266–74. doi:10.1056/NEJMra0907731. PMID 20592294.
- ↑ 2.0 2.1 2.2 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
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