Fondaparinux (Arixtra) is an indirect factor Xa inhibitor. It lacks cross-reactivity with heparin-induced antibodies and can be administered to patients diagnosed with HIT. Since it is 100 percent renally cleared, the patient must have a creatinine clearance of at least 30 mL/minute and preferably more than 50 mL/minute. It is typically weight-dosed, with 5 mg/day SC prescribed daily for patients less than 50 kg, 7.5 mg daily if the patient weighs 50–100 kg, and 10 mg/day SC for patients weighing more than 100 kg.

Rivaroxaban (Xarelto) is an oral direct factor Xa inhibitor. It may be used for acute and long-term treatment of DVT. As with LMWHs, it may not be appropriate for use in patients with renal insufficiency. It is typically started at 15 mg orally twice daily for three weeks, then 20 mg orally each day. It has been shown to be non-inferior to LMWHs, with similar or fewer major hemorrhages.

Apixaban (Eliquis), another factor Xa inhibitor, is administered at 10 mg orally twice daily for 10 days, then at 5 mg daily thereafter. Edoxaban (Savaysa), the third approved factor Xa inhibitor, is typically dosed at 60 mg orally per day, although it has been dosed at 15–30 mg daily for patients weighing less than 60 kg or with a creatinine clearance of 15–50 mL/minute. All of the factor Xa inhibitors are relatively expensive compared to warfarin, with 30-day cost to pharmacy cited in the $277–$315 range.⁸

There are no approved reversal agents for the factor Xa inhibitors. It should be noted that several molecules are being studied as potential reversal agents for NOACs.⁹ When there is an effective reversal agent available, NOAC indications may broaden.² It is unclear how effective prothrombin complex concentrates (PCCs) are in reversing anticoagulation effects of the factor Xa inhibitors, but they may be a treatment option for now until specific antidotes are approved.

Dabigatran etexilate (Pradaxa) is a direct thrombin inhibitor dosed typically at 150 mg twice daily orally for patients with creatinine clearance of more than 30 mL/minute after seven to 10 days of parenteral anticoagulation. It is approved for treatment of VTE in the United States. For emergency bleeding or for preparation for emergency surgery, a monoclonal antibody idarucizumab (Praxbind) is available to reverse its effects, given in 2.5 gm IV for two doses, no more than 15 minutes apart.9 Supratherapeutic levels of dabigatran may occur in patients with decreased renal function.

Conclusions

The emergency physician has a variety of options for managing patients with DVT as outpatients. Clearly, patients’ renal function, reliability, and support system will dictate the optimal treatment course.