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 Table of Contents  
Year : 2020  |  Volume : 4  |  Issue : 1  |  Page : 12-14

Timing and dose of pharmacological thromboprophylaxis in adult trauma patients

1 Department of Critical Care Medicine (MBC 94), King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
2 Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
3 Department of Critical Care Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
4 Department of Biostats and Epidemiology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Date of Submission05-Feb-2020
Date of Decision17-Feb-2020
Date of Acceptance24-Feb-2020
Date of Web Publication30-Apr-2020

Correspondence Address:
Mohammed Bawazeer
Department of Critical Care Medicine (MBC 94), King Faisal Specialist Hospital and Research Centre, P. O. Box: 3354, Riyadh 11211
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sccj.sccj_10_20

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Pharmacological venous thromboembolism prophylaxis in the trauma population is considered a real challenge. Issues like the ideal time to start therapy, type and dose of the medication, and how to monitor these patients are controversial. We searched PUBMED, EMBASE, and COCHRANE Databases. We also extracted the references from major review articles and recent guidelines. The timing to start thromboembolic prophylaxis in patients with traumatic brain injuries, Spinal Cord Injuries (SCI), and solid organ injuries is not very well defined in the literature. This is because of the associated bleeding risk. At the same time, the type of chemical prophylaxis and dose are not well defined as well. In this review, we present the most up to date studies done on this topic. We discuss the areas of controversy and the challenges behind starting chemical prophylaxis. We also discuss areas of future research potentials to do multicenter studies through the Saudi Critical Care Trials Group.

Keywords: Pharmacological prophylaxis, solid organ injuries, spinal cord injury, traumatic brain injury, venous thromboembolism prophylaxis

How to cite this article:
Bawazeer M, Amer M, Maghrabi K, Amin R, De Vol E, Hijazi M. Timing and dose of pharmacological thromboprophylaxis in adult trauma patients. Saudi Crit Care J 2020;4:12-4

How to cite this URL:
Bawazeer M, Amer M, Maghrabi K, Amin R, De Vol E, Hijazi M. Timing and dose of pharmacological thromboprophylaxis in adult trauma patients. Saudi Crit Care J [serial online] 2020 [cited 2021 May 8];4:12-4. Available from: https://www.sccj-sa.org/text.asp?2020/4/1/12/283638

  Introduction Top

Venous thromboembolism (VTE) has been linked with high morbidity, mortality in all hospital admissions with increasing costs. Trauma patient's population is one of the groups at the highest risk of VTE. The reported incidence ranges from 40% to 80% without prophylaxis. Risk factors that increase the risk for VTE in trauma include spinal cord injury, pelvic fracture, femur fracture, obesity, high-energy blunt trauma, traumatic brain injury (TBI), Greenfield Risk Assessment Profile of five points or greater, and Injury Severity Score >9.[1],[2] The risk of VTE increases substantially when starting VTE prophylaxis is delayed beyond the first 24 h.[1],[2] When prophylaxis is started after 4 days of hospital admission, the risk VTE increases three-fold in the severely injured patient. The pulmonary embolism (PE) risk increases by 80% with delayed prophylaxis compared to day 1 initiation.[1],[2],[3] The major cause of delays in starting prophylaxis is the risk/benefit ratio of bleeding to clot prevention. Moreover, there is limited evidence to date to conclude robust recommendations regarding the timing and dose of pharmacological venous thromboembolism prophylaxis (PVTE-Px) [Table 1].
Table 1: American College of Chest Physicians 9th edition and eastern association for the surgery of trauma guideline for thromboprophylaxis in major trauma patients

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Patients with TBI are at high risk for VTE due to hypercoagulability resulting from the primary brain injury, immobilization, and focal motor deficits. At the same time, initiating early PVTE-Px increases the risk of extension of intracranial hemorrhage. Variability exists in clinical practice guidelines recommendation with regard to the optimal timing of safely initiating PVTE-Px in TBI. According to the brain trauma foundation, if the brain injury is stable and the benefit is considered to outweigh the risk of increased intracranial hemorrhage, prophylaxis may be considered. However, there is not enough evidence suggesting the best agent, dose, or timing.[4] The 2017 neurocritical care society guidelines recommended low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) within 24 h of TBI and 24-h postcraniotomy.[5] Early initiation of PVTE-Px is also supported by the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) Best Practice Guidelines on TBI. These guidelines referred to the modified Berne-Norwood criteria to stratify injury risk of TBI progression and recommended to start PVTE-Px within 24 h (if low risk) or 72 h (if moderate risk) of injury in patients with stable head CT scan.[3] A review of the literature showed nonstatistically significant difference in ICH expansion if PVTE-Px is started before 3 days or after 3 days in TBI patients.[6] More recently, a meta-analysis published by Mesa Galan et al. examined the safety of early PVTE-Px initiation after TBI.[7] They included four studies (1371 patients) to evaluate the efficacy of early (in the first 72 h after TBI) versus late PVTE-Px in preventing VTE. The results were in favor of early administration (odds ratio, 0.46; 95% confidence interval, 0.24–0.88; P < 0.05). There was no significant difference regarding safety. Finally, there is no consensus regarding safety of initiating thromboembolic prophylaxis in the presence of intracranial pressure (ICP) monitors. However, one recent retrospective review found no association of increased risk of bleeding extension with the use of LMWH with invasive monitoring.[8]

The spinal cord injuries patients represent is a group that has a substantially increased risk of developing VTE with an incidence ranges from 49% to 72%.[9] Starting early thromboembolic prophylaxis makes a perfect sense to lower the incidence of VTE, but it can result in complications, such as spinal hematoma. Moreover, the timing of thromboembolic prophylaxis is not well defined in the EAST and ACCP guidelines. The 2017 neurocritical care society guideline recommended starting LMWH or UFH within 72 h of admission, which is consistent with the recommendation from the American Association of Neurological Surgeons and Congress of Neurological Surgeons.[5] A study by Christie et al. suggested that thromboembolic prophylaxis should be started within 72 h after SCI, held before the spine-related surgery, and maybe recommenced within 24 h following surgery.[9] A 2-year retrospective analysis of all isolated spinal trauma patients from the ACS-TQIP who were managed nonoperatively and received early PVTE-Px showed a reduction of VTE and PE rate without any difference in blood transfusion requirement and decompressive laminectomy.[10] Chang et al. studied the safety of early PVTE-Px in patients with spinal cord injuries who were operatively managed. The study showed that early PVTE-Px was not linked with an increased risk of intraspinal hematoma expansion.[11]

Solid organs injuries (SOI) are commonly associated with abdominal trauma. Nonoperative (NOR) management of SOI has evolved dramatically in recent years in the hemodynamically stable patient.[12] With this evolution, PVTE-Px may have to be withheld in the first 24 h of admission until the hemoglobin is stable. Several retrospective studies and literature reviews demonstrated that early PVTE-Px within 48 h is linked with a reduction of VTE incidence but without increased bleeding risk. There is a 2-year retrospective study of ACS-TQIP for adult trauma patients with blunt SOI who were managed nonoperatively. The patients were divided into three groups based on the timing of PVTE-Px (early ≤48 h of injury; late >48 h of injury; and no prophylaxis group). The authors found that the early PVTE-Px group had lower incidence rates of deep-vein thrombosis (DVT) (P = 0.01) and PE (P = 0.01) when compared to the other two groups. There was no difference with regard to post prophylaxis packed red blood cell transfusions, failure of NOR management, and mortality in the three groups.[13]

Regarding the specific PVTE-Px agent, literature and guidelines suggest that LMWH is superior to UFH because it has a lower incidence rate of DVT and PE.[1],[2] With regards to the dose, neither the ACCP nor the EAST practice management guidelines give a recommendation of LMWH-specific thromboembolic prophylaxis dosing. Trauma patients are at risk of augmented renal clearance (ARC), which is reported to be 67%–85%, resulting in reduced anti-Xa level leading to reduced efficacy of LMWH.[14] Therefore, alternative regimens have been suggested in the literature, which includes a higher initial dose regimen, dose calculated according to the patients' weight, or adjusted dose based on anti-Xa level.[15]

  Conclusion Top

The current timing, drug of choice, and dose of PVTE-Px in multiply injured patients are yet to be determined. We conducted a cross-sectional, survey-based study through the Saudi Critical Care Trials Group. The survey was distributed to intensivists, trauma surgeons, general surgeons, spine orthopedics, and neurosurgeons practicing in trauma centers to assess our practice pattern of PVTE-Px initiation in TBI, SCI, and NOR-SOI and describe factors influencing decision-making in Saudi Arabia. We observed variation in PVTE-Px initiation time influenced by trauma type compared to the evidence-based clinical data and clinicians' perception. Our findings suggested limited awareness of ARC and the role of the anti-Xa level. More prospective data and randomized studies are warranted to research these clinically important questions.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Rogers FB, Cipolle MD, Velmahos G, Rozycki G, Luchette FA. Practice management guidelines for the prevention of venous thromboembolism in trauma patients: The EAST practice management guidelines work group. J Trauma 2002;53:142-64.  Back to cited text no. 1
Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic therapy and prevention of thrombosis, 9th ed.: American college of chest physicians evidence-based clinical practice guidelines. Chest 2012;141:7S-47S.  Back to cited text no. 2
The ACS TQIP Best Practice Guidelines Management of Traumatic Brain Injury. Available from: https://www.facs.org/quality-programs/trauma/tqp/center-programs/tqip/best-practice. [Last accessed on 2019 Nov 14].  Back to cited text no. 3
Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 2017;80:6-15.  Back to cited text no. 4
Sauro KM, Soo A, Kramer A, Couillard P, Kromm J, Zygun D, et al. Venous thromboembolism prophylaxis in neurocritical care patients: Are current practices, best practices? Neurocrit Care 2019;30:355-63.  Back to cited text no. 5
Abdel-Aziz H, Dunham CM, Malik RJ, Hileman BM. Timing for deep vein thrombosis chemoprophylaxis in traumatic brain injury: An evidence-based review. Crit Care 2015;19:96.  Back to cited text no. 6
Mesa Galan LA, Egea-Guerrero JJ, Quintana Diaz M, Vilches-Arenas A. The effectiveness and safety of pharmacological prophylaxis against venous thromboembolism in patients with moderate to severe traumatic brain injury: A systematic review and meta-analysis. J Trauma Acute Care Surg 2016;81:567-74.  Back to cited text no. 7
Dengler BA, Mendez-Gomez P, Chavez A, Avila L, Michalek J, Hernandez B, et al. Safety of chemical DVT prophylaxis in severe traumatic brain injury with invasive monitoring devices. Neurocrit Care 2016;25:215-23.  Back to cited text no. 8
Christie S, Thibault-Halman G, Casha S. Acute pharmacological DVT prophylaxis after spinal cord injury. J Neurotrauma 2011;28:1509-14.  Back to cited text no. 9
Khan M, Jehan F, O'Keeffe T, Hamidi M, Truitt M, Zeeshan M, et al. Optimal timing of initiation of thromboprophylaxis after nonoperative blunt spinal trauma: A propensity-matched analysis. J Am Coll Surg 2018;226:760-8.  Back to cited text no. 10
Chang R, Scerbo MH, Schmitt KM, Adams SD, Choi TJ, Wade CE, et al. Early chemoprophylaxis is associated with decreased venous thromboembolism risk without concomitant increase in intraspinal hematoma expansion after traumatic spinal cord injury. J Trauma Acute Care Surg 2017;83:1088-94.  Back to cited text no. 11
Schellenberg M, Benjamin E, Piccinini A, Inaba K, Demetriades D. Gunshot wounds to the liver: No longer a mandatory operation. J Trauma Acute Care Surg 2019;87:350-5.  Back to cited text no. 12
Skarupa D, Hanna K, Zeeshan M, Madbak F, Hamidi M, Haddadin Z, et al. Is early chemical thromboprophylaxis in patients with solid organ injury a solid decision? J Trauma Acute Care Surg 2019;87:1104-12.  Back to cited text no. 13
Cook AM, Hatton-Kolpek J. Augmented renal clearance. Pharmacotherapy 2019;39:346-54.  Back to cited text no. 14
Berndtson AE, Costantini TW, Lane J, Box K, Coimbra R. If some is good, more is better: An enoxaparin dosing strategy to improve pharmacologic venous thromboembolism prophylaxis. J Trauma Acute Care Surg 2016;81:1095-100.  Back to cited text no. 15


  [Table 1]


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