Proceedings from the 2022 Consensus Conference to Implement Optimal Venous Thromboembolism (VTE) Prophylaxis in Trauma

Abstract

On May 4–5, 2022, a meeting of multidisciplinary stakeholders in the prevention and treatment of venous thromboembolism (VTE) after trauma was convened by the Coalition for National Trauma Research (CNTR), funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH/NHLBI), and hosted by the American College of Surgeons (ACS) in Chicago, Illinois. This consensus conference gathered more than 40 in-person and 80 virtual attendees, including trauma surgeons, other physicians, thrombosis experts, nurses, pharmacists, researchers, and patient advocates. The objectives of the meeting were two-fold: 1) to review and summarize the present state of the scientific evidence regarding VTE prevention strategies in injured patients, and 2) to develop consensus on future priorities in VTE prevention implementation and research gaps.

To achieve these objectives, the first part of the conference consisted of talks from physician leaders, researchers, clinical champions, and patient advocates to summarize the current state of knowledge of VTE pathogenesis and prevention in patients with major injury. Video recordings of all talks and accompanying slides are freely available on the conference website. (https://www.nattrauma.org/research/research-policies-templates-guidelines/vte-conference/) Following this curriculum, the second part of the conference consisted of a series of small-group breakout sessions on topics potentially requiring future study. Through this process, research priorities were identified and plans of action to develop and undertake future studies were defined.

The 2022 Consensus Conference to Implement Optimal VTE Prophylaxis in Trauma answered the National Trauma Research Action Plan call to define a course for future research into preventing thromboembolism after trauma. A multidisciplinary group of clinical champions, physicians, scientists, and patients delineated clear objectives for future investigation to address important, persistent key knowledge gaps. The series of papers from the conference outline the consensus based on the current literature and a roadmap for research to answer these unanswered questions.

On May 4–5, 2022, a meeting of multidisciplinary stakeholders in the prevention and treatment of venous thromboembolism (VTE) after trauma was convened by the Coalition for National Trauma Research (CNTR), funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH/NHLBI), and hosted by the American College of Surgeons (ACS) in Chicago, Illinois. This consensus conference gathered more than 40 in-person and 80 virtual attendees, including trauma surgeons, other physicians, thrombosis experts, nurses, pharmacists, researchers, and patient advocates. The objectives of the meeting were two-fold: 1) to review and summarize the present state of the scientific evidence regarding VTE prevention strategies in injured patients, and 2) to develop consensus on future priorities in VTE prevention implementation and research gaps.

To achieve these objectives, the first part of the conference consisted of talks from physician leaders, researchers, clinical champions, and patient advocates to summarize the current state of knowledge of VTE pathogenesis and prevention in patients with major injury (Table 1). Video recordings of all talks and accompanying slides are freely available on the conference website. (https://www.nattrauma.org/research/research-policies-templates-guidelines/vte-conference/) Following this curriculum, the second part of the conference consisted of a series of small-group breakout sessions on topics potentially requiring future study (Table 2). Fostering future scientific leaders in the field, these breakout sessions were facilitated by early-career trauma surgeon recipients of four CNTR Young Investigator Travel Awards and two early-career trauma surgeons supported by the American Association for the Surgery of Trauma (AAST) and the Eastern Association for the Surgery of Trauma (EAST) in conjunction with established surgeon-scientist mentors. Through this process, research priorities were identified and plans of action to develop and undertake future studies were defined.

Table 1.

Overview of Organizers, Funded Early-Career Trauma Surgeon Travel Awardees, Speakers and Topics at the 2022 Consensus Conference to Implement Optimal Venous Thromboembolism (VTE) Prophylaxis in Trauma

Conference Co-Directors
Todd Costantini, MD	University of California San Diego
Elliott R. Haut, MD PhD	Johns Hopkins University
Funded Early-Career Trauma Surgeon Travel Awardees
Navpreet Dhillon, MD	University of Maryland	NIH/NHLBI Funded
Ashanthi Ratnasekera, MD	Christiana Hospital	NIH/NHLBI Funded
Morgan Schellenberg, MD	University of Southern California	NIH/NHLBI Funded
Amanda Teichman, MD	Rutgers Robert Wood Johnson	NIH/NHLBI Funded
Lucy Z. Kornblith, MD	University of California San Francisco	AAST Funded
James Byrne, MD, PhD	Johns Hopkins University	EAST Funded
Speakers	Organization	Topic
Eileen Bulger, MD	Harborview Medical Center	Welcome and Opening Remarks
William Geerts, MD	Sunnybrook Health Sciences Centre	Overview of VTE in Trauma: Where have we been? Where are we going?
Eric Ley, MD	Cedars-Sinai Medical Center	Current Evidence-based Guidelines for VTE Prophylaxis
Ajai Malhotra, MD	University of Vermont	VTE as a Hospital Quality Indicator
Truman Milling, MD	University of Texas at Austin	Restarting Anticoagulation after Intracranial Hemorrhage
Bellal Joseph, MD	University of Arizona	DVT in Trauma: The Good, The Bad, and The Future
Thomas Beaumont, MD	University of California San Diego	VTE Prophylaxis: Neurosurgery Perspectives
Anna Miller, MD	Washington University in St. Louis	VTE Prophylaxis: Orthopedic Surgery Perspectives
M. Margaret Knudson, MD	University of California San Francisco	Overview and Update on CLOTT Studies
Elliott R. Haut, MD PhD	Johns Hopkins University	Overcoming Barriers to Delivering VTE Prophylaxis
Alok Khorana, MD	Case Western Reserve University	VTE Prophylaxis Post-Discharge
Mary Cushman, MD	University of Vermont	Health Disparities in VTE
Leslie Lake	National Blood Clot Alliance	The Patient Perspective
Rachel Kruer, PharmD	Indiana University Health	The Future of Pharmacologic VTE Prophylaxis: Are Direct Oral Anticoagulants the Answer?
Deborah Stein, MD	University of Maryland	The Aspirin Study: From ADAPT to PREVENT CLOT
John Fanikos, RPh MBA	Brigham & Women’s Hospital	Does Aspirin Have a Role in VTE Prevention in Trauma?
Todd Costantini, MD	University of California San Diego	Current Research Gaps: Review of National Trauma Research Agenda (NTRAP) Delphi Survey Results
Avery Nathens, MD PhD	Sunnybrook Health Sciences Centre	Utilizing the TQIP Infrastructure to Measure Outcomes and Implementation
Elliott R. Haut, MD PhD	Johns Hopkins University	Implementation Science Approaches and Outcome Measurement
Andrei Kindzelski, MD PhD Thuy-Vy Do, PhD Margie Shofer, BSN MBA COL Andrew Cap, MD	NHLBI – NIH PCORI AHRQ US Army Inst. of Surgical Research	Extramural Funding Opportunities and Priorities

VTE- Venous Thromboembolism

TQIP- Trauma Quality Improvement Program

CLOTT - Consortium of Leaders in the Study of Traumatic Thromboembolism

NIH/NHLBI- National Institutes of Health / National Heart, Lung, and Blood Institute

PCORI- The Patient Centered Outcomes Research Institute

AHRQ- Agency for Healthcare Research & Quality

Table 2.

Topics for Break-out Sessions to Determine Future Research Priorities at the 2022 Consensus Conference to Implement Optimal Venous Thromboembolism (VTE) Prophylaxis in Trauma

Timing of initiation of VTE prophylaxis for patients with high-risk injuries

Implementation of best practice early VTE prevention

Novel pharmacologic agents for VTE prevention

New approaches to optimizing VTE prevention

Extending VTE prophylaxis after acute hospitalization

Treatment of trauma-associated de novo pulmonary thrombosis

The Patient Perspective: Central to the Mission

The patient must remain central to every mission in health care. Leslie Lake, the volunteer President of the National Blood Clot Alliance (NBCA), joined the conference to share her experience. When Leslie was struck by the sudden onset of shortness of breath in 2018, she did not expect ever to be standing before a room of medical professionals to tell her story four years later. Her interaction with the healthcare system would be formative. She presented to a busy emergency department in New York City, where she would subsequently undergo nine hours of waiting punctuated by evaluations that seemed unrelated to her symptoms, including three gynecologic examinations. On the verge of being discharged home with a diagnosis of fibroids, one provider prompted a CT angiogram of the chest which identified a pulmonary embolism (PE). She was promptly admitted to the intensive care unit.

Leslie passionately told her story of the considerable disconnect between her experience as a patient and the medical infrastructure around her. She received minimal information and so set about educating herself about blood clots. Discharged on apixaban, she found that her outpatient supports were few and opinions regarding her care plan were conflicting. Her journey of self-education led her to the NBCA. This organization’s website gave her the knowledge and language to advocate for herself (https://www.stoptheclot.org). She also found that as a finance professional, she was in a position that enabled her to navigate a complex health system to gain access to the ongoing medical care she needed. Through this process, she was struck by despair and anger that many people would not have been in a similar position to advocate for themselves. Leslie chose to act, to work so that others might not have to experience the disconnect that she had. She joined the NBCA Board of Directors and soon became its volunteer President.

The NBCA is a non-profit, patient-led advocacy organization founded in 2003 (1). Its formation stemmed from a collaboration between patients and researchers at the Centers for Disease Control (CDC), and work with the CDC is ongoing. Four-fifths of the NBCA’s Board of Directors are survivors or family members of those afflicted by VTE, and it is part of the organization’s charter that 50% of board members are patients. The organization’s mission is to advance the prevention, early diagnosis, and treatment of life-threatening thromboembolism. Supported by a Medical and Scientific Advisory Board, public engagement and education are the primary part of this mission.

Since 2015, the signature Stop the Clot, Spread the Word^® initiative has reached more than 100 million people through its online resources (1). Several aspects of NBCA’s initiatives seek to target disparities in the incidence, treatment, and outcomes of VTE. Specifically, the Health Disparities Initiative is a quality improvement initiative aimed at improving health outcomes for African Americans affected by blood clots in rural areas, and the Health Equity Institute consists of an advisory council of Black VTE patients and healthcare providers focused on improving care in predominantly Black communities (2). The Women and Blood Clots initiative is dedicated to women’s unique risks and care needs, including VTE associated with hormone replacement therapy, birth control, and pregnancy. The Sports and Wellness Institute seeks to raise awareness that athletes are a vulnerable, often underdiagnosed population.

Patients remain at the center of the NBCA mission. Patients Educating Patients (PEP Talk) is a patient-driven support community. The Critical Look at Understanding the Emotional Suffering (CLUES) Blood Clot Study seeks to evaluate the emotional well-being of VTE patients, recognizing that post-traumatic stress is common among survivors (3).

Taken together, through the advocacy and work of patients like Leslie Lake, the NBCA provides a forum for VTE researchers to remain connected with the patient experience to ensure that this remains central to their mission. NBCA has provided the critically important patient voice to numerous PCORI funded projects related to VTE in trauma and non-trauma patient populations.

A Brief History of Venous Thromboembolism Research in Injured Patients

Dr. William Geerts led off the scientific curriculum of the conference, providing context with his nearly 30-year experience as one of the pre-eminent researchers in the field of VTE after trauma. Thromboembolism as a life-threatening complication after injury was first described long before the current era of trauma specialization. Paul von Bruns reported the occurrence of PE after fracture in 30 patients, many of which were fatal, in 1885 (4). Sevitt and Gallagher, in an autopsy series from the Birmingham Accident Hospital published in 1961, found deep vein thromboses (DVT) in 81% of trauma decedents (5). Of most significant concern, the authors concluded that more than 1% of all trauma admissions died of PE. In one of the first venography studies of trauma survivors published in 1967, Freeark et al. found that DVT occurred in 35% of immobilized patients, many of which were sub-clinical (6). Despite these findings, the pervasive opinion of the time was that “routine prophylactic treatment with anticoagulation may produce more trouble than it prevents” due to residual bleeding risk. These early investigations culminated in a call for action in the first thromboprophylaxis guidelines published by the National Institutes of Health Consensus Panel on VTE in 1986 (7). It was recognized that the “risks of thromboembolic diseases… have not been defined for the general trauma population” and the “efficacy and safety of various forms of prophylaxis have not been evaluated in patients with multisystem trauma.”

Based on the recognized need for high-quality investigation, Geerts et al. performed their landmark prospective study using venography in 349 consecutive admissions with severe injury (8). No mechanical or pharmacologic thromboprophylaxis was administered in this cohort that had a mean injury severity score (ISS) of 27. Venography identified DVT in 58% of patients, 18% of which were proximal DVT. This study identified independent risk factors for VTE in trauma, a list further built upon in subsequent studies (8–12) (Table 3). These data, confirming that major trauma patients are at very high risk for developing VTE, coincided with a time of increasing recognition of trauma as a unique disease process requiring sub-specialized care. As a result, the investigation into the subject has blossomed over the past three decades (Figure 1A).

Table 3.

Risk Factors for Venous Thromboembolism (VTE) in Trauma

Age

Transfusion

Surgery

Injury severity score (ISS)

Pelvic or lower extremity fracture

Spinal cord injury

Major head injury

Major venous injury

Femoral venous catheter

Reduced mobility

Delay in VTE prophylaxis initiation

Missed doses of VTE prophylaxis

Figure 1.

Dramatic Increases Over Time for Papers Published about (A) Venous Thromboembolism (VTE) and (B) (VTE) Prophylaxis in Trauma Patients

Effective prevention of thromboembolic complications became a leading priority in trauma research (Figure 1B). Early literature proposing use of pharmacologic agents for prophylaxis against VTE (13–15), while previously viewed with skepticism out of concern for persistent risk of hemorrhage after trauma, became the focus of renewed interest. Geerts et al. compared the effectiveness of low molecular weight heparin (LMWH; enoxaparin 30mg every 12 hours) to low-dose unfractionated heparin (UH; 5000 units every 12 hours) in their randomized controlled trial of consecutive patients with severe injury (16). Enoxaparin was associated with a 30% reduced risk of DVT overall, and 58% reduced risk of proximal DVT (number needed to treat = 11), as identified on venography. Major bleeding complications occurred in only 6 of 344 patients and were comparable between groups. Subsequent observational studies reconfirm that LMWH is superior to UH for prophylaxis against VTE in trauma patients (17–19) which is suggested by most guidelines (20, 21).

With pharmacologic VTE prophylaxis being the most effective means of prevention, the safe timing of initiation of prophylaxis has become a subject of vigorous evaluation. Geerts et al. demonstrated that bleeding risk is low in the majority of patients (16). Furthermore, many VTE events occur early during the acute admission. In one mixed trauma cohort from 34 level I and II trauma centers, the median times to identify DVT and PE were 7 and 4 days, respectively (22). Similarly, Sing et al. reported that over 50% of pulmonary emboli occurred within seven days of injury (23). This risk increases with each successive day that prophylaxis is delayed (17, 22). For this reason, early initiation within 24 hours of injury should be the standard for most injured patients. Exceptions to this practice have included specific subgroups in which the perceived risk of hemorrhage or its consequences persist. These groups include patients with traumatic brain injury, spinal cord injury, vertebral or pelvic fracture, and solid organ injury. While there is evidence that timely initiation of pharmacologic VTE prophylaxis is feasible without precipitating hemorrhagic complications in these populations (24–27), this continues to be an area of ongoing clinical debate and investigation.

As thromboprophylaxis practices evolved, inferior vena cava (IVC) filters have been used as an adjunctive primary prophylactic measure in patients with perceived contraindications to prophylactic anticoagulation. While some studies have indicated that IVC filters may reduce the risk of fatal PE (28), others have shown no association with patient survival (29). Ho et al. subsequently showed in their randomized controlled trial of 240 severely injured patients that prophylactic IVC filter use did not reduce the risk of symptomatic PE or mortality (30). Added to concerns of cost, variable utilization, low rates of removal (31), and potential morbidity, these data support that IVC filter use for primary prophylaxis should be limited and highly-selective. Guidelines now recommend against the use of IVC filters as primary prophylaxis in almost all cases (20, 21, 30). The guidelines emphasize that IVC filters should be used as part of adjunctive treatment for patients diagnosed with VTE in highly-select instances, such as patients with PE or proximal DVT in whom therapeutic anticoagulation is contraindicated. In these cases, structured follow-up is required to determine when resumption of anticoagulation is safe, to ensure filter retrieval, and detect complications (32).

Further efforts to prevent potentially fatal PE have included screening high-risk, asymptomatic patients with duplex ultrasound for early identification of DVT. Research to determine the effectiveness of this approach has been confounded by wide practice variation (33). Higher screening utilization leads to surveillance bias in rates of DVT detection (12, 34), a hospital quality indicator, and does not appear to translate into lower rates of PE in mixed trauma cohorts (35, 36). However, routine duplex screening in patients with high-risk injury patterns may be justified (37) and cost-effective (38). A prospective randomized trial published in 2021 found that screening in patients with high risk-assessment scores was associated with fewer PE (39). The added benefit of this approach over and above a rigorous protocol for timely pharmacologic prophylaxis remains uncertain. Both WTA and AAST/COT guidelines recommend that routine screening only be performed in this high-risk patient subgroup.

Further optimization of pharmacologic VTE prophylaxis through dose adjustment has become a subject of great interest. Sub-therapeutic levels of anti-Factor Xa are found in the majority of trauma patients at conventional doses of LMWH (40, 41). Protocols utilizing a higher starting dose LMWH (typically 40mg every 12 hours) and dose adjustment based on anti-Factor Xa levels have been associated with reduced rates of VTE (42). However, some studies have shown no benefit to dose adjustment using anti-Factor Xa levels (43, 44), and weight-based adjustment protocols may represent a simpler, less costly approach to achieving the goal of prophylactic effect (45–47).

Current Guidelines for Optimal Venous Thromboembolism Prophylaxis After Trauma

Based on the scientific work of the past 30 years, it should now be feasible to minimize the risk of major VTE events (symptomatic or fatal PE and extensive DVT) without precipitating hemorrhage complications. This can be achieved through up-to-date, evidence-based protocols. The first published recommendations by a trauma professional organization for the prevention of VTE were the Eastern Association for the Surgery of Trauma (EAST) practice management guidelines in 2002 (48). Twenty years later, the Western Trauma Association (WTA) (21) and jointly the American Association for the Surgery of Trauma (AAST) with the American College of Surgeons Committee on Trauma (COT) (20) have published their own evidence-based algorithms. Dr. Eric Ley provided an overview of similarities and differences between these guidelines.

Agent Selection, Dose, and Timing of Initiation

Both WTA and AAST/COT guidelines recommend LMWH over UH for thromboprophylaxis. This is due to the high-quality level I and subsequent observational data that LMWH is likely superior to UH for VTE prevention (16–18). Studies that reported equivalence were likely either underpowered or could not control important factors related to patient selection (49, 50). The use of LMWH also dramatically reduces, if not eliminates, the risk of heparin-induced thrombocytopenia, which is not insignificant with UH (51, 52).

Both guidelines now recommend LMWH 40mg every 12 hours. This is an increase from the previous standard dosing (30mg every 12 hours) due to data demonstrating that the majority of patients require at least 40mg every 12 hours to achieve target levels of anti-Factor Xa (41).

Both guidelines emphasize the early initiation of pharmacologic VTE prophylaxis to reduce risk of VTE due to delay (17, 22). The WTA recommends initiation within 24 hours of injury, while the AAST/COT recommends immediate initiation in patients without active bleeding or high-risk injuries (TBI, spinal cord injury, or solid organ injury).

High Risk Injuries

While WTA and AAST/COT guidelines both prioritize early initiation of thromboprophylaxis, their approaches to achieve this in patients with TBI, spinal cord injury, or solid organ injury differ. Timely initiation in all injuries appears feasible without increasing risk of hemorrhagic complication (26, 53–59). The WTA guideline recommends initiation of prophylaxis within 24 hours of bleeding cessation, spinal fixation, or stability of intracranial hemorrhage. In contrast, the AAST/COT recommends following the Modified Berne-Norwood Criteria for TBI (54), and initiating prophylaxis within 48 hours after spinal cord or solid organ injury (58, 59). Both guidelines recommend commencing a lower dose of pharmacologic prophylaxis for these patients (LMWH 30mg every 12 hours), reflecting a lack of data to demonstrate safety of higher dosing in these populations.

Missed Doses of Pharmacologic VTE Prophylaxis

Both societies emphasize that thromboprophylaxis should be continuous and without interruption. Missed doses of VTE prophylaxis are significantly associated with increased risk of VTE (60, 61). Furthermore, the practice of holding pharmacologic prophylaxis for surgical procedures out of fear of bleeding complication is not based on evidence. In Geerts’ 1996 landmark trial, prophylaxis was not withheld for surgical procedures except for spinal fixation (for which only one pre-operative dose was held) (16).

Dose Adjustment and Special Populations

Both the WTA and AAST/COT discuss dose adjustment based on weight and anti-Factor Xa levels. The AAST/COT recommends weight-based dosing first for patients with body mass index greater than 30 kg/m² using LMWH 0.5mg/kg every 12 hours (62), a provision that is not made by the WTA. Both guidelines recommend adjusting LMWH dosing to achieve target anti-Factor Xa levels (peak 0.2 – 0.4 IU/mL or trough 0.1 – 0.2 IU/mL) after initiation, citing literature to support lower rates of VTE with this approach (41, 42, 63).

Specific populations of patients may require lower dosing of LMWH to achieve goal anti-Factor Xa levels. Creatinine clearance (CrCl) should dictate the dose required to achieve target prophylactic effect. For this reason, both guidelines agree that patients with impaired renal function (CrCl 30 – 60 mL/min) should receive lower dosing (30mg every 12 hours). This recommendation is also made for patients over 65 years of age, with very low body weight (< 50kg), or pregnant. Patients with CrCl < 30 mL/min are recommended to receive UH by both guidelines.

Deriving Consensus on Future Research Directions

Despite guidelines from two professional trauma associations based on nearly three decades of scientific evidence, the optimal practice for preventing VTE after trauma remains unclear. Practice variation persists owing to clinical uncertainty and barriers to implementing best-practice prevention into routine clinical care. Todd Costantini described results from a consensus process called the National Trauma Research Action Plan (NTRAP) (64) which has already identified four major research gaps of high priority in the area of VTE: 1) implementation of early best practice VTE prevention, 2) timing of initiation of VTE prophylaxis in patients with high-risk injuries, 3) approaches to optimizing VTE prophylaxis, and 4) evaluating use of novel pharmacologic agents for VTE prophylaxis.

Representatives from funding agencies, including the Agency for Healthcare Research & Quality (AHRQ), the National Institutes of Health / National Heart, Lung, and Blood Institute (NIH/NHLBI), the Patient-Centered Outcomes Research Institute (PCORI), and the United States Army Institute of Surgical Research, delivered a panel session titled “Extramural Funding Opportunities and Priorities.” Avery Nathens spoke about research opportunities to leverage the existing infrastructure of the American College of Surgeons Trauma Quality Improvement Program (TQIP) to perform studies (whether prospective cohort, randomized trials, or retrospective observational) and build additional data elements such as structural, process, or outcomes data points into TQIP for individual trauma centers to contribute additional data to answer these questions.

Implementation of Early Best Practice VTE Prevention

Delays in initiation and interruption of pharmacologic VTE prophylaxis significantly increase risk of DVT and potentially life-threatening PE (17, 22, 60). Furthermore, the use of VTE prophylaxis in patients with high-risk injuries remains highly variable (65). Education for clinicians, clinical decision support tools for risk assessment, patient-centered education, and computerized alerts have been demonstrated to improve prescription and adherence to VTE prophylaxis in medical and surgical patients (66–70). However, there remains a knowledge gap regarding the application, potential effectiveness, and cost of such interventions to improve implementation of VTE prophylaxis in trauma patients. Based on the breakout sessions at the VTE Consensus Conference, Ratnasekera et al. summarize the state of the literature on this subject and present their proposal for future research directions to improve implementation of VTE prophylaxis best practices (71).

Timing of Initiation of Pharmacologic VTE Prophylaxis in High-Risk Patients

Perhaps the subject of greatest clinical uncertainty is achieving timely but safe initiation of pharmacologic VTE prophylaxis in patients at high-risk for hemorrhagic complications. Patients with TBI and intracranial hemorrhage are at particularly high risk for hemorrhage expansion. For this reason, significant practice variation exists, both with respect to selection of prophylactic agent and timing. A major contributor to this practice variation is heterogeneity with respect to patterns of injury. While several studies support that timely initiation of prophylaxis can be achieved without risking harm due to hemorrhage expansion (53, 55–57), other data raise the potential for adverse events in patients with highest-risk injuries (72). However, these studies are predominantly observational in nature without adequate granularity to be conclusive. Similarly, studies that support the safety of early initiation of prophylaxis in patients with solid organ or spinal cord injuries are mainly single center or retrospective (26, 58, 59). Summarizing the evidence and discussion from the VTE Consensus Conference, Schellenberg et al. present their recommendations for future studies to clarify this knowledge gap (73).

Approaches to Optimizing VTE Prophylaxis Dosing in Trauma Patients

While the superiority of LMWH over UH for thromboprophylaxis in trauma patients has been established, the best approach to achieving optimum prophylactic effect remains unclear. Dose-adjustment based on anti-Factor Xa levels is currently recommended in WTA and AAST/COT guidelines (20, 21) based on studies that showing the benefit of reduced VTE rates (41, 42, 63). However, other studies show no association between adjustment based on anti-Factor Xa level and rates of VTE (43). There is evidence that differences in serum antithrombin III may be implicated in the association between observed anti-Factor Xa levels and effectiveness of heparinoid prophylaxis (74). Furthermore, there are studies that support a purely weight-based dosing approach to achieve adequate prophylaxis (45–47). Thromboelastographic findings have also been correlated with risk of VTE (75). A more in-depth summary of these data is presented by Teichman et al. who discuss their recommendations for future research into these mechanisms for the purpose of optimizing VTE prescription dosing prevention strategies (76).

Novel Pharmacologic Agents for VTE Prophylaxis in Trauma

While subcutaneous heparins have become the standard for pharmacologic VTE prophylaxis in trauma, there may be alternatives with similar effectiveness. Oral agents, such as aspirin or direct oral anticoagulant medications, may be preferred by patients if they could achieve the goal of prevention while avoiding repeated injections – a common reason for patient refusal (77, 78). Deborah Stein spoke about a large, ongoing PCORI-funded randomized trial comparing aspirin vs. LMWH in orthopedic trauma patients (79). Based on the VTE Consensus Conference, Dhillon et al. review the current evidence for aspirin or direct oral anticoagulant agents as VTE prophylaxis in trauma patients and makes recommendations for future research into their use (80).

Conclusions

The 2022 Consensus Conference to Implement Optimal VTE Prophylaxis in Trauma answered the National Trauma Research Action Plan call to define a course for future research into preventing thromboembolism after trauma. A multidisciplinary group of clinical champions, physicians, scientists, and patients delineated clear objectives for future investigation to address important, persistent key knowledge gaps. The series of papers from the conference outline the consensus based on the current literature and a roadmap for research to answer these unanswered questions (71, 73, 76, 80).