CHAPTER 100 DIAGNOSIS AND TREATMENT OF DEEP VENOUS THROMBOSIS: DRUGS AND FILTERS

The association between injury and venous thromboembolic events is well accepted in trauma patients. The incidence in deep venous thrombosis varies from 7% to 58% depending on the demographics of the patients, nature of the injuries, method of detection, and the type and timing of prophylaxis used in the study population.¹^–⁴ It is thought that the high incidence of deep venous thrombosis in the trauma population can be attributed to the altered physiologic states and anatomic derangements that often coexist in these patients. Virchow’s triad of stasis, vessel injury, and hypercoagulability often are present in these patients. Venous stasis is promoted by prolonged bed rest, patient immobilization, paralysis, and hypoperfusion, none of which are uncommon in trauma patients. In addition, hypercoagulability may be induced by diminished levels of antithrombin III, suppression of fibrinolysis, or other alterations in the coagulation system. Finally, the presence of endothelial damage, caused by direct vascular injury, can result in intimal damage and eventually thrombus.

Prevention of thromboembolic events in patients that are simultaneously at high risk for deep venous thrombosis (DVT) formation and bleeding poses a difficult challenge to the trauma surgeon. This challenge is compounded by the fact that more than 60% of DVTs are clinically occult.^5,⁶ The usual signs and symptoms of DVT, such as swelling and pain, are often obscured by injury.

Many studies have been completed in an attempt to stratify trauma patients into high-risk subgroups for the development of DVT. Traditionally, pelvic and lower extremity fractures, head injury, and prolonged immobilization are considered critical risk factors for DVT formation.^1,^2,^4,^7,⁸ In addition, large volume blood transfusions raise the likelihood of DVT. Current evidence clearly implicates spinal cord injury and spinal fractures as high-risk conditions.⁹ Older age also predisposes to thrombosis, although the exact transition point is unclear.¹⁰^–¹² Other factors that may also place patients at a higher risk for DVT development, but are not well studied or agreed upon, include injury severity score (ISS) and large transfusion volume.

The nidus for thrombus formation occurs at the time of injury, thus trauma patients do not have the opportunity for true prophylaxis. Concomitant conditions may prohibit usual prophylaxis techniques by days to weeks. In contrast, patients undergoing elective surgery receive preemptive intervention prior to any inciting event. This differentiation likely explains the sharp difference in the incidence of DVT in the trauma population as well as why standard methods of prophylaxis are less effective in preventing posttraumatic venous thromboembolism.

CURRENT THERAPIES

Definitive randomized controlled clinical studies on prophylactic measures in trauma patients with multiple injuries do not exist. Unlike other surgical patients, injured patients are a heterogeneous group who have an isolated injury or any combination of injuries making stratification extremely complicated. Additionally many patients are excluded from one type of prophylactic measure or another by the nature of their injury. With these limitations in mind, there is literature to help guide the development of prophylactic regimens.

SEQUENTIAL COMPRESSION DEVICES

The use of sequential compression devices (SCD) is attractive because of the low complication rate associated with their use. However, with the exception of head injured patients, SCDs have been shown to offer little benefit over no specific prophylaxis.¹³ Problems with mechanical compression devices in trauma patients are accessibility and compliance. Many trauma patients require casting or external fixation limiting accessibility to the lower extremity, making use of mechanical compression devices difficult or impossible. Shackford et al.⁷ noted that venous compression devices could not be placed at all in 35% of trauma patients because of traction, edema, external fixators, or casts. Lack of compliance is a major contributing factor in the failure of mechanical compression devices in trauma patients. Given the short-lived antithrombotic effect of SCD, even limited periods of noncompliance may encourage clot formation.^7,¹⁴ In a prospective study of 227 patients, only 19% were fully compliant with physician orders for SCD prophylaxis.¹⁵ Venous foot pumps, once thought of as a substitute for SCD in situations in which the calves were inaccessible, have been shown to be insufficient prophylaxis.

LOW-DOSE HEPARIN

In the general surgery population, low-dose heparin decreases the rate of DVT formation. Although the low rate of bleeding complications associated with the use of low-dose heparin would make it well suited for use in trauma, several studies reveal low-dose heparin to be relatively ineffective in preventing DVT in the subset of higher-risk trauma patients.¹⁶^–¹⁸

LOW-MOLECULAR-WEIGHT HEPARIN

Low-molecular-weight heparin (LMWH) gained popularity in the late 1990s as an effective method of DVT prophylaxis in trauma patients. In a randomized double-blinded trial comparing LMWH to low-dose heparin in trauma patients, LMWH reduced the overall DVT rate by 30%, although both groups had a high incidence of DVT formation.¹⁷ Subsequent clinical evaluations and recent guidelines support the safety and efficacy of enoxaparin in trauma patients who do not have substantial bleeding risk.^16,¹⁹^–²³ Clinical experience with other LMWH is increasing in the trauma population. A single-center evaluation of 743 high-risk trauma patients who received dalteparin 5000 IU SQ daily reported rates of proximal DVT and nonfatal PE as 3.9% and 0.8%, with a corresponding 3% rate of significant bleeding.²⁴ Preliminary data in spinal cord injury suggest that dalteparin 5000 IU daily and enoxaparin 30 mg twice daily have comparable bleeding risks while providing similar protection from DVT.²⁵ Caution is necessary in extrapolating therapeutic equivalence among LMWH agents, due to differences in dose equivalences, pharmacokinetics, administration times and DVT/PE diagnosis used in clinical trials.

INFERIOR VENA CAVA FILTERS

Trauma patients are often not candidates for adequate pharmacologic prophylaxis or therapeutic anticoagulation when a DVT is documented. These patients may, however, be candidates for the placement of an inferior vena cava filter. Currently there are no randomized and very few prospective studies on the use and long-term outcomes of inferior vena cava filters (IVC filters). IVC filters do not prevent DVT formation. They are intended to reduce the risk of pulmonary embolism (PE), and specifically, fatal pulmonary embolism. It should be noted that this has not been consistently proven, especially when used prophylactically. Some, in fact, argue that IVC filters actually promote DVT formation and may result in caval thrombosis and the long-term postphlebitic syndrome.²⁶^–²⁸ Other authors report a decrease in the incidence of pulmonary embolism versus historical controls. Still others cite no change in the incidence of pulmonary embolism, persistence of morbidity from DVT, or long-term outcomes. Filter complications include migration, tilt, caval perforation, and PE.^26,²⁹^–³³ In 2002, the Eastern Association for the Surgery of Trauma published its practice management guidelines for the prevention of venous thromboembolism in trauma patients. Although there were no class I data to support prophylactic vena cava filter placement in high-risk trauma patients, there was a reasonable amount of retrospective and case series data to support the recommendation for consideration of prophylactic vena cava filter insertion in high-risk patients who cannot receive anticoagulation.²² DVT formation in the trauma patient is theorized to result from local effects of the inflammatory response in combination with venous stasis. The at-risk period in these patients is relatively short and well-defined, making the use of permanent vena cava filters, with their associated risks, less appealing. Retrievable vena cava filters, on the other hand, are thought to offer the same protection as permanent filters during the period of greatest risk, while later retrieval might avoid long-term risk.^34,³⁵ Although several filters have the indication for temporary use and, therefore, would be appropriate in trauma patients, recent literature shows a significant number of “temporary filters” are not retrieved for reasons including lack of follow-up by patients, technical difficulty, and ongoing risk that exceed the time window for filter removal.³⁶^–³⁹ There are also concerns about embolization and the need for anticoagulation during retrieval of temporary IVC filters, which may outweigh the benefit that these temporary filters provide.