Venous Thromboembolism Prevention in the Morbidly Obese Medically Ill Patient: A Pharmacological Analysis of the Predictability of Prophylactic Weight-Based Enoxaparin Dosing.

Background and Introduction:

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in hospitalized patients. It is a well-known complication in patients after major surgery or trauma. More recently, medically ill patients have been identified as another high risk group with up to 15% of patients experiencing VTE in the absence of prophylaxis. 1 Several studies have found the use of enoxaparin, dalteparin, and fondaparinux to be safe and effective in reducing risk of VTE by 45% to 63% in medically ill patients. 1-3 Additionally, enoxaparin has been found to be at least as safe and effective as unfractionated heparin for VTE prophylaxis. 4 Enoxaparin 40 mg once daily has been shown to be a safe and effective prophylactic therapy in hospitalized patients. 1

In thromboprophylaxis studies, including those investigating enoxaparin 40 mg once daily, morbidly obese patients (greater than or equal to 35 kg/m2) have been grossly under-enrolled. This is problematic for several reasons. First, the drug distribution is weight dependent and therefore, anticoagulant levels will differ according to a patient's weight. 5 Secondly, the FDA approved doses are fixed doses that do not take into account body weight. Thirdly, obese patients are at greater risk for failure in preventing VTE and obese patients are probably at greater risk for developing VTE. 6 Lastly, morbidly obese patients are becoming quite common as the population as a whole is becoming more obese.

Even with this information, there are no standards of VTE prophylaxis in obese patients. Optimal means of delivering safe and effective thromboprophylaxis in this group is unknown. When using LMWH's, consensus recommendations have been to monitor peak anti-Xa activity targeting a level of 0.1-0.2 units/mL. 5 However, many hospitals do not have access to anti-Xa monitoring. Studies evaluating the predictability of weight-based prophylactic dosing of tinzaparin have demonstrated that anti-Xa levels are predictably achieved and therefore, laboratory monitoring may not be necessary with this dosing strategy.7 However, tinzaparin is not widely utilized in the U.S. and uncertainties remain about whether predictable anti-Xa levels can be achieved with a weight-based prophylactic regimen using the more commonly used drug enoxaparin. If weight-based dosing with enoxaparin is shown to result in predictable anti-Xa activity in obese patients, the need for monitoring would be obviated.

Objectives: The primary objective is to evaluate the predictability in achieving target anti-Xa activity levels in morbidly obese medically ill patients using weight-adjusted (0.5 mg/kg) once daily prophylactic dose of enoxaparin. The secondary objective is to gain information to evaluate the pharmacokinetic curve of enoxaparin in obese patients over 18 hours after the second dose.