Original Article: Deep Venous Thrombosis and Pulmonary Embolism: Current Therapy

Issue Date: March 1, 2017

See additional reader comments at: https://www.aafp.org/afp/2017/0301/p295.html

To the Editor: We read the article on venous thromboembolism (VTE) with interest and appreciate that the authors highlight the different treatment options for this disease state. Given the limited data regarding treatment of VTE in patients who are morbidly obese (body mass index [BMI] of 40 kg per m² or more) and that the current prevalence of morbid obesity in the United States is around 8%,¹ family physicians must keep weight and BMI in mind when considering direct oral anticoagulants and low-molecular-weight heparin (LMWH) for VTE treatment.

The International Society on Thrombosis and Haemostasis offers some guidance.² Standard dosing of direct oral anticoagulants should still be considered for VTE prevention and treatment for patients with a BMI less than or equal to 40 kg per m² or weight less than or equal to 264 lb (120 kg). For patients with a BMI greater than 40 kg per m² or weight more than 120 kg, direct oral anticoagulants should not be considered a first-line therapy because of limited clinical data and evidence suggesting decreased exposure, concentration, and half-lives at the weight extremes.

However, the International Society on Thrombosis and Haemostasis suggests that for patients who are morbidly obese who cannot use a vitamin K antagonist (warfarin [Coumadin]), physicians might consider checking anti–factor Xa peak and trough levels (for apixaban [Eliquis], edoxaban [Savaysa], and rivaroxaban [Xarelto]). It should be noted that all data regarding anti– factor Xa levels used tests specifically calibrated for the drug being tested or mass spectrometry drug levels. Continuing the direct oral anticoagulant is reasonable if the level falls within the expected range, but changing to a vitamin K antagonist is recommended, if possible, if the drug level is below the therapeutic range.²

If a vitamin K antagonist and bridging with LMWH is used, it is also important to note the limited data and different pharmacokinetic and pharmacodynamic properties in patients who are morbidly obese. The LMWH agent enoxaparin (Lovenox) has no official dosing recommendations for these patients,³ but data in this population suggest that a reduced weight-based dose (less than 1 mg per kg) is warranted.^4,5 A retrospective cohort of 99 patients with BMI greater than 40 kg per m² or weight more than 331 lb (150 kg) showed that more than 50% of patients had supratherapeutic peak anti–factor Xa levels using normal weight-based dosing of 1 mg per kg of enoxaparin.⁴ A prospective dosing study also showed an average enoxaparin dose of 0.71 mg per kg for therapeutic effects.⁵ Therefore, it is also important for physicians to consider starting LMWH at lower doses and consider monitoring peak anti–factor Xa concentrations in patients who are morbidly obese.

In Reply: We thank Drs. Gibbs and Sheley for raising an important issue regarding our article. We agree that direct oral anticoagulant use in patients with a BMI greater than 40 kg per m² has not been adequately studied and should be avoided. Although monitoring peaks and troughs in anti–factor Xa levels in patients who are morbidly obese and treated with factor Xa inhibitors may help safely guide therapy in this population, these laboratory assays are not readily available to most family physicians. In our experience, treatment of acute VTE in patients who are morbidly obese is most safely achieved by using intravenous unfractionated heparin and concomitant warfarin.