/publications/health-system-edition/2012/May-2012/Pharmacist-Rounds1

Ambulatory Care: Anticoagulation

Author: Whitney D. Maxwell, PharmD, BCPS

Ambulatory Care: Anticoagulation

Case

RT is a 44-year-old woman with a history of right lower extremity deep vein thrombosis (DVT) 1 month after surgery for right tibia fracture repair, morbid obesity (weight = 177 kg), and tobacco dependence. She was initiated on warfarin therapy and enoxaparin 170 mg subcutaneously BID for DVT treatment, but could not tolerate warfarin due to extreme malaise. The patient was subsequently transitioned to fondaparinux 10 mg subcutaneously daily as monotherapy and anti-Xa monitoring was recommended by the hematology clinic. The primary care provider ordered an anti-Xa level for 3 to 4 hours post-dose, which resul-ted as 1.04 anti-Xa IU/mL. The clinical pharmacist was consulted to assist with interpretation of the level.

Answer

Fondaparinux is a parenterally administered selective factor Xa inhibitor that is FDA approved for treatment of venous thomboembolism (VTE). Currently, the safety and efficacy of fondaparinux use in patients with morbid obesity is not well established due to the scarcity of literature in this population. The recommended treatment dosage for VTE in patients weighing more than 100 kg is 10 mg subcutaneously daily, but for patients in significant excess of 100 kg, as in this patient’s case, the ability of the 10-mg daily dose to provide adequate anticoagulation is uncertain.

Fondaparinux use for short-term treatment of DVT in obesity was evaluated in the MATISSE-DVT trial, which was published in the Annals of Internal Medicine in 2004. In the MATISSE-DVT study, 119 study subjects weighed >100 kg and received fondaparinux 10 mg daily. There was no significant difference in the primary outcomes of VTE or major bleeding in the overall study population, but separate p values for the subgroup of patients >100 kg and the range of patient weights were not reported. Thus, the greatest weight in which fondaparinux 10 mg daily has demonstrated safety and efficacy is unknown.

Anti-Xa levels can be used to assess low molecular weight heparin’s (LMWH’s) antithrombotic activity in obese patients. However, because fondaparinux is a direct Factor Xa inhibitor and not an LMWH, the LMWH anti-Xa assay that was ordered for this patient cannot be interpreted. A fondaparainux-specific anti-Xa assay would be required instead. The utility of a fondaparinux-specific anti-Xa assay for this patient is also limited by the absence of a definitive correlation between fondaparinux anti-Xa levels and safety and efficacy outcomes. Additionally, fondaparinux doses of greater than 12 mg were associated with increased risk of puncture site bleeding in acute coronary syndrome patients in the PENTUA study, so the utility of fondaparinux monitoring in obesity is limited by the inability to safely recommend higher doses. The pharmacist’s role in this patient’s case was to describe limitations of the current clinical evidence and prevent interpretation of a lab test that was ordered incorrectly.


Dr. Maxwell is clinical assistant professor in the department of clinical pharmacy and outcomes sciences at South Carolina College of Pharmacy in Columbia, South Carolina.