RESPIRATORY MEDICINE MADE SIMPLE : TREATMENT OF PULMONARY EMBOLISM

 

TREATMENT OF PULMONARY EMBOLISM

Anticoagulation for Pulmonary Embolism

Unfractionated heparin therapy

In patients with acute PE, anticoagulation with IV UFH, LMWH, or fondaparinux is preferred over no anticoagulation. Most patients with acute PE should receive LMWH or fondaparinux instead of IV UFH. If IV UFH is chosen, an initial bolus of 80 U/kg or 5000 U followed by an infusion of 18 U/kg/h or 1300 U/h should be given, with the goal of rapidly achieving and maintaining the aPTT at levels that correspond to therapeutic heparin levels. Fixed-dose and monitored regimens of subcutaneous UFH are available and are acceptable alternatives.

Low-molecular-weight heparin therapy

Current guidelines for patients with acute PE recommend LMWH over IV UFH (grade 2C) and over SC UFH (grade 2B).  In patients being treated with LMWH, once-daily regimens are preferred over twice-daily regimens (grade 2C). The choice between fondaparinux and LMWH should be based on local considerations to include cost, availability, and familiarity of use.

LMWHs have many advantages over UFH. These agents have a greater bioavailability, can be administered by subcutaneous injections, and have a longer duration of anticoagulant effect. A fixed dose of LMWH can be used, and laboratory monitoring of aPTT is not necessary.

Direct thrombin inhibitors and factor Xa inhibitors

Apixaban, dabigatran, rivaroxaban, and edoxaban are alternatives to warfarin for prophylaxis and treatment of PE. Apixaban, edoxaban, and rivaroxaban inhibit factor Xa, whereas dabigatran is a direct thrombin inhibitor.

Rivaroxaban

Rivaroxaban (Xarelto) is an oral factor Xa inhibitor approved by the FDA in November 2012 for the treatment of DVT or PE, and to reduce risk of recurrent DVT and PE following initial treatment.

Fondaparinux

In patients with acute PE, fondaparinux as initial treatment is favored over IV UFH and over SC UFH.The choice between fondaparinux and LMWH should be based on local considerations to include cost, availability, and familiarity of use. Fondaparinux is a synthetic polysaccharide derived from the antithrombin binding region of heparin. Fondaparinux catalyzes factor Xa inactivation by antithrombin without inhibiting thrombin.

 

Warfarin therapy

A vitamin K antagonist such as warfarin should be started on the same day as anticoagulant therapy in patients with acute PE. Parenteral anticoagulation and warfarin should be continued together for a minimum of at least five days and until the INR is 2.0.

The anticoagulant effect of warfarin is mediated by the inhibition of vitamin K–dependent factors, which are II, VII, IX, and X. The peak effect does not occur until 36-72 hours after drug administration, and the dosage is difficult to titrate.

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