The Use of Fondaparinux in Preventing Thromboembolism in High-Risk Trauma Patients
Trauma patients are at high risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE). The incidence of DVT varies greatly from 5-63, depending on the patient’s individual risk factors, modality of prophylaxis, and methods of detection. The incidence of pulmonary embolism (PE) may be as low (0.3-4.3%) but carries a mortality of 20-50% which makes prevention of DVT of the utmost importance. The trauma community continues to search for a more perfect method of DVT prophylaxis. At San Francisco General Hospital, we are currently enrolling patients into a study where we are using fondaparinux in place of the current standard, enoxaparin. Fondaparinux has been studied in orthopedic populations and its efficacy may be superior to enoxaparin, however, the drug’s efficacy and safety has not yet been established in trauma patients. This study is sponsored by the manufacturer of the drug, GlaxoSmithKline.
The study is designed to include all patients over 18 years of age admitted to the trauma service after acute injury who have at least one risk factor for DVT. Risk factors for DVT are defined as age greater than forty years, pelvic fractures, lower extremity fractures, shock, spinal cord injury, head injury, major operative procedure, ventilator requirements greater than three days, and venous injury.
Patients are then sub-grouped into those who can get pharmacologic anticoagulation and those who cannot, secondary to a clinical contraindication such as a head injury or renal failure. Patients who can get pharmacologic anticoagulation are given fondaparinux for DVT prophylaxis during their hospital stay. Patients who cannot get pharmacologic anticoagulation get mechanical compression devices until the treating physicians believe it is safe to start anticoagulation, at which point the patient will be given fondaparinux. All participants in the study undergo ultrasound surveillance of both upper and lower extremities for DVTs on arrival and weekly thereafter for up to three weeks. At the end of three weeks, the patient’s participation ends, fondaparinux is discontinued regardless of the patient’s subgroup, and choice of DVT prophylaxis is left up to the treating physicians.
A secondary aim is to study how fondaparinux affects anti-Xa activity in these patients. To do so, we are collecting anti-Xa activity at the drug’s trough and peak around the 3rd or 4th dose.
We have enrolled 106 patients in the study and enrollment ended in June, 2008. Ninety-nine patients were subgrouped to get fondaparinux. Ten patients initially had contraindications for fondaparinux, but the majority of these patients crossed over to getting fondaparinux after the first week of hospitalization. Thus far, we have noted two DVTs, one in a posterior tibial vein in an ambulating patient and one in the axillary and brachial vein of an ICU patient. Both patients were receiving fondaparinux at the time of DVT diagnosis. Regarding adverse events, several patients have had decreases in hematocrits that were treated with blood transfusions. In no case was the decrease attributed to the fondaparinux but rather to the patient’s injuries. In all these cases, only a single dose of fondaparinux was held.
The goal of this project is to demonstrate that this drug is as least as effective as enoxaparin (projected DVT rate of less than 5%) and that it is safe to use. After evaluation of the data, including the anti-Xa activity, a multi-center study may be initiated to establish the effectiveness of this drug in preventing post-injury thromboembolic events. The data is being analyzed in preparation for publication. This project is coordinated by JP Lu, MD, a mid-level surgery resident who has spent her research year at the San Francisco Injury Center.