Venous Thromboembolism in Trauma: The Role of Anticoagulation and Inferior Vena Cava Filters

Abstract

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality among patients with severe trauma. Historically, prophylactic inferior vena cava filters (IVCFs) were used in high-risk trauma patients with suspected risk factors for VTE, including prolonged immobilization, and concurrent contraindication to anticoagulation. Mounting data regarding the efficacy of IVCF in this cohort, as well as concerns regarding morbidity of an in situ IVCF, have challenged this practice paradigm. In this review, we discuss the comanagement of VTE and trauma, including anticoagulation and the use of IVCF.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality among patients with severe traumatic injuries. ¹ Prospective studies have shown that proximal deep vein thrombosis (DVT) occurs in as many as 18% of trauma patients and pulmonary embolism (PE) in 11% (vs. 1 to 2 per 1,000 patients per year in nontraumatic patients). ^{1 2} In patients with more severe injuries, especially involving the pelvic or long bones, studies suggest that VTE can occur in up to 80% of patients. ² Fatal PE accounts for more than 12% of all deaths and 6% of preventable death after major trauma. ^{2 3 4 5 6} Classically, acquired VTE is believed to occur through some combination of Virchow's triad, which includes stasis, endothelial injury, and hypercoagulability. By virtue of their injuries and the ensuing clinical sequelae, the majority of patients with severe trauma are thus at high risk for development of VTE; immobility secondary to injuries results in venous stasis, severe injury activates a prothrombotic state through dysregulation of the coagulation cascade, and trauma can result in direct damage to the endothelium. ^{7 8 9 10} Moreover, pharmacologic VTE prophylaxis is often directly contraindicated in trauma patients due to the presence of active bleeding or the risk of developing active bleeding in critical structures, such as the central nervous system, in the presence of anticoagulation. Historically, these factors have been the impetus for prophylactic inferior vena cava filter (IVCF) placement, often early in the clinical course. ² In this review, we discuss the use of anticoagulation and IVCF in the prevention of PE in trauma patients through an examination of literature that both supports and challenges their use.

Pharmacologic Prophylactic Anticoagulation in Trauma

Pharmacologic prophylactic anticoagulation should be considered as first-line prophylaxis before IVCF placement. Numerous systemic reviews and meta-analyses of randomized controlled trials have demonstrated significantly reduced risk for DVT with the use of prophylactic anticoagulation, although no reduction in PE or mortality. ^{11 12 13 14 15 16 17} Two randomized trials demonstrated lower risks of DVT with low-molecular-weight heparin (LMWH) compared to unfractionated heparin. While several new medical agents for the prevention of VTE are now available, these medications have not yet been thoroughly studied in patients with traumatic injury and are neither routinely used nor recommended. Compared to unfractionated heparin, LMWH is preferred for its improved bioavailability, longer half-life, and improved efficacy against factor Xa while inducing less of an effect on platelets and microvascular permeability, two factors which are thought to contribute to anticoagulation-related hemorrhage. ¹⁸ Based on these data, the American College of Chest Physicians (ACCP) recommend that all hospitalized trauma patients who do not have a contraindication to pharmacologic antithrombotic therapy receive prophylactic dose LMWH in addition to lower extremity mechanical compression. ¹⁹

While no high-level evidence is available regarding dosage of LMWH among trauma patients, several studies have suggested that prophylactic dosing does not achieve adequate anti-Xa levels, and that therapeutic dosing may be required. ^{20 21 22} However, increased dosages achieving adequate anti-Xa levels may result in higher bleeding risk. In a study of 45 trauma or surgical patients, higher fixed dosage of LMWH used to achieve target anti-Xa levels resulted in increased risk of bleeding complications. ²³ Together, these data raise the concern that the required effective dosage in trauma patients may not be permissible in those with severe injuries or those with a high risk for hemorrhage.

Pharmacologic VTE prophylaxis in patients with solid organ injury or traumatic brain injury (TBI) remains the most controversial topic in management. Historically, any anticoagulation was deemed contraindicated in TBI; however, there is mounting evidence demonstrating that it may be both safe and efficacious. In a retrospective study of over 3,000 patients, early initiation of pharmacologic VTE prophylaxis within 72 hours halved the rate of VTE without an increase in risk of death or surgical intervention for new or expanding intracranial hemorrhage. ²⁴ Several similar studies have corroborated these results in patients treated within 24 to 48 hours. ^{25 26} These data culminated in guidelines by the American College of Surgeons and Brain Trauma Foundation, who support early initiation of LMWH in the setting of stable head CT imaging. ²⁷

Observational studies in patients with solid-organ trauma and stabilized hemoglobin have not shown increased rates of bleeding with prophylactic pharmacologic thromboprophylaxis initiated within 48 hours. ^{28 29 30} However, no definitive guidelines are available. Therefore, several experts have recommended the initiation of VTE prophylaxis within 48 hours, after the hemoglobin has stabilized as defined by minimal change in a 24-hour time period.

Historical Use of Inferior Vena Cava Filters in Patients with Traumatic Injury

The risk of VTE is highest in the early clinical course and sharply rises if pharmacologic prophylaxis is delayed beyond 72 to 96 hours. ³¹ In one study, up to 37% of symptomatic PE occurred within the first 4 days. ³² Since there is often concern for evolving or developing hemorrhage in the immediate posttraumatic period (particularly among those with head or solid-organ trauma), IVCFs have classically been considered as a reasonable alternative to pharmacologic prophylaxis in severely injured patients. ^{33 34}

Historically, support for the use of IVCFs in trauma patients has been driven by small retrospective and observational studies. Several early case series suggested that prophylactic IVCF in trauma patients reduced the risk of symptomatic and fatal PE when IVCFs are used in patients who do not receive pharmacologic thromboprophylaxis. ^{5 33 34} These data culminated in the 2002 Eastern Association of Trauma (EAST) guidelines suggested that prophylactic IVCF be considered for high-risk trauma patients with suspected prolonged immobilization and with a contraindication to prophylactic medical anticoagulation ( Table 1 ). ³⁵

Table 1. EAST guidelines for prophylactic IVC filter placement in trauma patients (Level III evidence).

Prophylactic IVC filter insertion should be considered in very high-risk trauma patients without documented DVT or PE:
Who cannot receive anticoagulation because of increased bleeding risk
High risk for bleeding complications for 5–10 days after injury would include those with intracranial hemorrhage, ocular injury with associated hemorrhage, solid intra-abdominal organ injury (i.e., liver, spleen, kidney), and/or pelvic or retroperitoneal hematoma requiring transfusion. Other risk factors for bleeding include cirrhosis; active peptic ulcer disease; end-stage renal disease; and coagulopathy caused by injury, medication, or congenital/hereditary. In addition, it appears that age is a significant risk factor for VTE, but it is unclear at what age risk of VTE significantly increases. The need to place a prophylactic VCF may be increased in an older patient with one of the earlier-mentioned injuries
Who have an injury pattern rendering them immobilized for a prolonged period of time, including the following:
1. Severe closed head injury (GCS score <8)   2. Incomplete spinal cord injury with paraplegia or quadriplegia   3. Complex pelvic fractures with associated long-bone fractures   4. Multiple long-bone fractures

Abbreviations: DVT, deep vein thrombosis; EAST, Eastern Association for the Surgery of Trauma; GCS, Glasgow Coma Scale; IVC, inferior vena cava; PE, pulmonary embolism; VCF, vena cava filter.

Since the 2002 EAST guidelines, several studies have reported that in situ IVCFs are associated with a host of previously unsuspected device-related complications, including device fracture, component embolization, DVT, inferior vena cava thrombosis, and device perforation into adjacent retroperitoneal structures. ³⁶ As the costs and potential risks of IVCF have become more apparent, there has been an increase in scrutiny of the appropriate indications for filter use.

A few systematic reviews and meta-analyses aimed at assessing the benefits of IVCF in trauma patients have resulted in conflicting results. A large systemic review and meta-analysis demonstrated an association between IVCF placement and lower incidence of PE and fatal PE in trauma patients. ³⁷ However, several others have failed to corroborate a similar conclusion. ^{38 39} Most of the available and included studies compare IVCF placement in addition to anticoagulation to anticoagulation alone, which ultimately fails to address whether IVCFs are beneficial in traumatic patients with active contraindications to anticoagulation. As such, the role of IVCF in trauma has historically been a topic of debate, with dramatically different management patterns throughout the United States. ^{40 41} Variability in the available data has resulted in conflicting guidelines from ACCP, EAST, and the Society of Interventional Radiology (SIR). ^{13 35 42} While EAST and SIR suggest prophylactic IVC filter use for high-risk patients with a contraindication to anticoagulation, the ACCP does not.

Recent Evidence in the Use of IVCF in Trauma Patients

Two recent studies have provided the highest quality analyses to date regarding the use of IVCF in the setting of trauma. A 2017 retrospective study aimed to assess whether IVCF use in trauma patients affected overall mortality. Stratified propensity matching of Injury Severity Score, head and neck Abbreviated Injury Score, age, sex, and race/ethnicity were used to select a matching control population. ⁴³ Among 451 trauma patients with an IVCF versus 1,343 matched controls without a filter, at a mean follow-up of 3.8 years, there was no significant difference in overall mortality in patients without an IVCF in those who survived beyond 24 hours. When assessing in-hospital mortality, there were significantly lower rates of inpatient death among patients with IVCF relative to the controls. The IVCF group had significantly higher Extremities Abbreviated Injury Scale scores, which historical data suggests is an increased risk factor for VTE among trauma patients. Therefore, the IVCF group could reasonably be expected to have increased rate of VTE, morbidity, and mortality. As there were significantly lower rates of inpatient death in the IVCF group and no difference at long-term follow-up, it may be suggested that the placement of IVCF may negate mortality from PE, especially in the immediate posttraumatic time period when the majority of trauma-related VTE morbidity and mortality occurs. However, this study was limited by the lack of propensity matching based on indications of IVCF insertion, and indications for IVCF were not reported for either group.

Only one randomized trial assessing the efficacy of IVCF in trauma patients has been performed ⁴⁴ ; this study enrolled 240 patients who underwent randomization for placement of a retrievable IVCF. All patients who were planned to receive anticoagulants within 72 hours from admission were excluded. Pharmacologic anticoagulation was initiated as soon as clinically feasible. Endpoints included symptomatic PE, death from any cause at 90 days, and DVT at 90 days. This study found that the incidence of symptomatic PE or death was not statistically lower in those receiving an IVCF at 90 days. In patients who survived 7 days and did not receive anticoagulation within 7 days, no patients with IVCF had symptomatic PE versus 5 patients in the control group. Among patients who did not receive anticoagulation within 7 days, 69% had intracranial hematomas or hemorrhage.

Other Considerations

The Angel catheter (Mermaid Medical, Stenlose, Denmark) is a device intended for mechanical caval prophylaxis in critically ill patients at high risk for PE. It consists of a self-expanding closed-cell design nitinol IVCF which is permanently attached to a triple lumen central venous catheter and is deployed from a femoral vein access. The major advantage of this device is the concurrent placement of a central venous catheter along with “guaranteed” retrieval of the filter when the catheter is removed. However, if central venous access is no longer needed and the catheter removed, a second procedure for IVCF placement would be needed to maintain mechanical prophylaxis. There are limited data evaluating its efficacy and safety, and no specific study of its use in trauma patients has been performed. A few small studies have shown favorable safety profiles and efficacy in preventing PE. ^{45 46 47 48}

A number of PE risk scoring systems have been developed in trauma patients which may help stratify patients into high-risk groups that may benefit more from a prophylactic IVCF. ^{49 50 51} No previous studies have included a predictive scoring system when deciding which patients should receive prophylactic IVCF, and an interesting area of future research may be to incorporate such a scoring system to identify a subgroup of patients who have significantly increased benefit to IVCF placement. Select centers have used such scoring systems to assist in clinical decision making when assessing whether placement of an IVCF is appropriate.

Conclusion and Our Recommendations

Venous thromboembolism in patients with severe trauma can have a significant, deleterious role in patient outcomes. When possible, anticoagulation use should be first-line therapy. When this is not possible, careful patient selection for the placement of prophylactic IVCF is important for maximizing clinical benefit, while reducing risks associated with an in situ filter. At our center, management decision in patients with severe trauma without known VTE is taken in a multidisciplinary fashion. In patients whom are expected to have active contraindications to anticoagulation for greater than 7 days, especially in those with TBI, we advocate for the placement of an IVCF based on currently available evidence. As always, anticoagulation should be restarted as soon as clinically feasible, with prompt removal of the IVCF once no longer indicated. However, much work remains to be done to optimize outcomes for these patients; in addition to refining our understanding of which patients are most likely to benefit from an IVCF, we must also gather higher quality data to determine which trauma patients are truly at the greatest risk of VTE.