Venous thromboembolism in trauma patients: A review

doi:10.1067/msy.2001.114558

Surgery

Volume 130, Issue 1, July 2001, Pages 1-12

https://doi.org/10.1067/msy.2001.114558 Get rights and content

Abstract

Surgery 2001;130:1-12.

Section snippets

Incidence

The first reports of PE and DVT after trauma were from autopsy studies. In 1934, McCartney² documented that in 1604 trauma autopsies, PE was the cause of death in 61 patients (3.8%). In another necropsy study of trauma patients in 1961, Sevitt and Gallagher³ found a 65% incidence of DVT and a 20.3% incidence of PE. In a medical examiner report of 950 fatal injuries, Fitts et al⁴ found that PE was the cause of death in 143 patients (15%). In a 1976 autopsy study, Coon⁵ found that 14.3% of the

Pathophysiology

In 1856, Virchow¹¹ described a triad of conditions associated with the development of venous thrombosis. These included intimal injury, stasis, and hypercoagulability. All 3 conditions are frequently seen in the trauma patient soon after injury. Intimal injury may be present as a result of direct tissue destruction of venous blood vessel walls from the inciting traumatic event. Stasis may occur as a result of paralysis, immobilization, or decreased blood flow caused by hemorrhagic shock.

Risk factors for venous thromboembolism

Several studies have demonstrated high-risk factors for the development of VTE in trauma patients. Knudson et al⁶ showed that 4 variables were strongly associated with the occurrence of thromboembolic complications: older age (49 ± 23 versus 36 ± 17 years), days immobilized (23 ± 15 versus 10 ± 13 days), transfusions received (11 ± 12 versus 3 ± 5 U packed red cells), and a prolonged initial partial thromboplastin time (39 ± 28 versus 26 ± 5 seconds). Shackford et al⁷ observed that patients

Deep vein thrombosis

There are several diagnostic modalities used to detect DVT in trauma patients. These include physical examination, venography, impedance plethysmography, and ultrasound. Impedance plethysmography, although widely used in the past, will not be discussed here because it is a rarely used diagnostic modality, replaced primarily by ultrasound.

The most readily available and easiest to perform diagnostic modality to detect DVT in trauma patients is physical examination. Unfortunately, it is the least

Standard prophylaxis

SCH and VCB are the 2 prophylactic agents most commonly used in trauma patients. Heparin is a mucopolysaccharide of 6000 to 30,000 d that occurs naturally in the mast tissue cells of the lung, liver, and intestine. Its anticoagulant properties, thought to be the result of its strong electronegative charge, allow it to combine with many different proteins, including those of the coagulation cascade. Heparin works by combining with antithrombin III and forming a complex that inactivates

Investigational prophylaxis

Low-molecular-weight heparins (LMWH) are distillates of unfractionated heparin (UFH) of molecular weight 4000 to 5000 d (compared with 6 to 30,000 d for UFH). One effect of the smaller molecular weight is a longer plasma half-life resulting from fewer interactions with cells, platelets, and plasma proteins. Below a molecular weight of about 5.6 d, the LMWH tend to lose anti-IIa activity (and hence an inability to be reliably monitored with activated partial thromboplastin time).⁴⁸ They do

Complications

The most common complication related to pharmacologic prophylaxis with heparin is bleeding. This is of paramount concern in trauma patients with multi-system injuries who are at especially high risk for serious fatal complications from bleeding diathesis. Brathwaite et al⁷⁶ retrospectively reviewed the outcome of 70 “low-risk” trauma patients who were treated with anticoagulation for VTE. Complications developed in 36% of the patients, some of which were life threatening (3 subdural hematomas,

Decision analysis on prophylactic measures after trauma

The decision on which prophylactic measure to use on each patient is not always easy and not always based on irrefutable data in the literature. As such, venous thromboprophylaxis is still a relatively inexact science. Despite these limitations, a few practical guidelines may prove useful in the decision analysis based on our management protocols at our institution (University of Vermont College of Medicine).

1.
A patient who is not considered at high risk (as previously discussed) and is

Future directions

During the past 5 years, several factors have been discovered that contribute to thrombosis in the role of coagulation abnormalities. It has now been demonstrated that resistance to activated protein C (first described in 1993)⁸⁶ caused by a mutation in clotting factor V (factor V Leiden) is prevalent in up to 5% of the general population.87, 88 Likewise, hypercoagulable abnormalities such as high levels of factor VIII (up to 11% of the general population)⁸⁹ or hyperhomocystinemia (up to 5% of

Summary

VTE is a problem that continues to plague trauma patients. Many of Virchow's triad (intimal injury, stasis, hypercoagulability) may already be present in the trauma patient with the time of their injury and may explain why there is a 7% to 12%6, 7 incidence of DVT and a 2% to 3%⁹ incidence of PE, despite adequate prophylaxis in recent studies. The highest-risk injuries appear to be those with spine fracture or spinal cord injury,4, 8 head injury,1, 2 lower-extremity fracture,1, 7, 8 and pelvic

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Cited by (94)

The effectiveness of venous thromboembolism prophylaxis interventions in trauma patients: A systematic review and network meta-analysis
2023, Injury
Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review provides evidence for the use of VTE prophylactic interventions in trauma patients to produce evidence-based guidelines.
A PRISMA-compliant review was conducted from Sep 2021 to June 2023, using Embase, Medline and Google Scholar. The inclusion criteria were: randomized-controlled trials (RCTs) in English published after 2000 of adult trauma patients comparing VTE prophylaxis interventions, with a sample size higher than 20. The network analysis was conducted using RStudio. The results of the pairwise comparisons were presented in the form of a league table. The quality of evidence and heterogeneity sensitivity were assessed. The primary outcome focused on venous thromboembolism (VTE), and examined deep vein thrombosis (DVT) and pulmonary embolism (PE) as separate entities. The secondary outcomes included assessments of bleeding and mortality. PROSPERO registration: CRD42021266393.
Of the 7,948 search results, 23 studies with a total of 21,312 participants fulfilled screening criteria, which included orthopaedic, spine, solid organ, brain, spinal cord, and multi-region trauma. Of the eight papers comparing chemical prophylaxis medications in patients with hip or lower limb injuries, fondaparinux and enoxaparin were found to be significantly superior to placebo in respect of prevention of DVT, with no increased risk of bleeding. Regarding mechanical prophylaxis, meta-analysis of two studies of inferior vena cava filters failed to provide significant benefits to major trauma patients.
Enoxaparin and fondaparinux are safe and effective options for VTE prevention in trauma patients, with fondaparinux being a cheaper and easier administration option between the two. Inconclusive results were found in mechanical prophylaxis, requiring more larger-scale RCTs.
Does tranexamic acid increase venous thromboembolism risk among trauma patients? A prospective multicenter analysis across 17 level I trauma centers
2023, Injury
The early use of tranexamic acid (TXA) has demonstrated benefit among some trauma patients in hemorrhagic shock. The association between TXA administration and thromboembolic events (including deep vein thrombosis (DVT), pulmonary embolism (PE) and pulmonary thrombosis (PT)) remains unclear. We aimed to characterize the risk of venous thromboembolism (VTE) subtypes among trauma patients receiving TXA and to determine whether TXA is associated with VTE risk and mortality.
We analyzed a prospective, observational, multicenter cohort data from the Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) study group. The study was conducted across 17 US level I trauma centers between January 1, 2018, and December 31,2020. We studied trauma patients ages 18–40 years, admitted for at least 48 h with a minimum of 1 VTE risk factor and followed until hospital discharge or 30 days. We compared TXA recipients to non-recipients for VTE and mortality using inverse probability weighted Cox models. The primary outcome was the presence of documented venous thromboembolism (VTE). The secondary outcome was mortality. VTE was defined as DVT, PE, or PT.
Among the 7,331 trauma patients analyzed, 466 (6.4%) received TXA. Patients in the TXA group were more severely injured than patients in the non-TXA group (ISS 16+: 69.1% vs. 48.5%, p < 0.001) and a higher percentage underwent a major surgical procedure (85.8% vs. 73.6%, p < 0.001). Among TXA recipients, 12.5% developed VTE (1.3% PT, 2.4% PE, 8.8% DVT) with 5.6% mortality. In the non-TXA group, 4.6% developed VTE (1.1% PT, 0.5% PE, 3.0% DVT) with 1.7% mortality. In analyses adjusting for patient demographic and clinical characteristics, TXA administration was not significantly associated with VTE (aHR 1.00, 95%CI: 0.69–1.46, p = 0.99) but was significantly associated with increased mortality (aHR 2.01, 95%CI: 1.46–2.77, p < 0.001).
TXA was not clearly identified as an independent risk factor for VTE in adjusted analyses, but the risk of VTE among trauma patients receiving TXA remains high (12.5%). This supports the judicious use of TXA in resuscitation, with consideration of early initiation of DVT prophylaxis in this high-risk group.
Low-Dose Heparin Infusion as Venous Thromboembolism Chemoprophylaxis in Patients With Blunt Cerebrovascular Injury
2023, Journal of Surgical Research
Blunt cerebrovascular injury (BCVI) can result in devastating stroke. Because of operative inaccessibility, the most common treatment for BCVI is aspirin or a low-dose systemic heparin infusion. While it is assumed that low dose heparin infusion imparts venous thromboembolism (VTE) prophylaxis, this has not been evaluated in the BCVI population. The purpose of this study was to evaluate VTE rates in patients receiving low-dose heparin infusion as treatment for BCVI.
Patients diagnosed with BCVI between 2014 and 2018 were reviewed for initiation of low-dose systemic heparin treatment. VTE was defined as a deep vein thrombosis or pulmonary embolism. BCVI patients without systemic heparin treatment were compared to BCVI patients with heparin treatment for overall VTE rates. Comparisons were also made to injured patients without a BCVI in our Trauma Activation Protocol (TAP) database.
During the 5-year study period, 265 patients were identified with a BCVI. The majority (61%) were men with a median injury severity score (ISS) 22 (interquartile range [IQR]:14-33). Of these patients, 146 (55.1%) received a heparin infusion to treat BCVI. VTE was identified in eight of these patients (5.5%). Compared to TAP patients (n = 1020) who received standard dosing of VTE chemoprophylaxis, there was no difference in VTE rates compared to BCVI patients who were started on a low dose heparin infusion (3% versus 5.5%, P = 0.16). Area under the receiver operating characteristics (AUROC) was used to evaluate the predictive power of time to initiation of heparin infusion (AUC = 0.64 95% CI 0.42-0.85, P = 0.2) and time to reaching PTT goal (AUC = 0.52 95% CI 0.27-0.77, P = 0.83) as a predictor VTE events.
Low dose heparin infusion is frequently used as an initial treatment of BCVI. In injured patients with BCVI, a low dose heparin infusion is associated with a low rate of VTE, comparable to injured patients without BCVI that received standard VTE chemoprophylaxis.
Direct Oral Anticoagulants Are a Potential Alternative to Low-Molecular-Weight Heparin for Thromboprophylaxis in Trauma Patients Sustaining Lower Extremity Fractures
2021, Journal of Surgical Research
Trauma patients are at a significant risk of venous thromboembolism (VTE), with lower extremity fractures (LEF) being independent risk factors. Use of direct oral anticoagusants (DOACs) for VTE prophylaxis is effective in elective orthopedic surgery, but currently not approved for trauma patients. The primary objective of this study was to compare the effectiveness and safety of thromboprophylaxis of DOACs with low-molecular-weight heparin (LMWH) in trauma patients sustaining LEF.
We included adult trauma patients admitted to trauma quality improvement program participating trauma centers (between 2013 and 2016), who sustained LEF and were started on DOACs or LMWH for thromboprophylaxis after admission. Propensity score matching was performed to compare symptomatic VTE and bleeding control interventions between the groups.
Of 1,009,922 patients in trauma quality improvement program, 167,640 met inclusion criteria (165,009 received LMWH and 2631 received DOACs). After propensity score matching, 2280 predominantly elderly (median age: 67 y) isolated femur fracture patients (median ISS: 10) were included in each group (4560 patients in total). Symptomatic VTE occurred in 1.4% of patients in both matched groups (P = 0.992). Bleeding control interventions occurred less often in the DOAC group, albeit statistically insignificant (5.8% versus 6.0%, P = 0.772).
This study found similar rates of VTE and bleeding control measures for thromboprophylaxis with DOACs or LMWH in matched trauma patients with LEF. Further prospective research is warranted to consolidate the safety of DOAC thromboprophylaxis in trauma patients with LEF. Favorable oral administration and likely increased adherence could benefit this high-risk population.
Admission thrombelastography does not guide dose adjustment of enoxaparin in trauma patients
2020, Surgery Open Science
Citation Excerpt :
Venous thromboembolism (VTE) is a significant source of morbidity and mortality in traumatically injured patients [1]. The interplay of Virchow's triad (ie, hemostasis or alteration of blood flow, endothelial injury, hypercoagulability) is often the underlying mechanism that results in development of VTE [2]. Derangements in clotting factors can occur, which produce a hypercoagulable response contributing to the formation of a thrombus [3–5].
Enoxaparin is used as chemoprophylaxis to reduce incidence of venous thromboembolism and its complications following trauma. Serum anti-Xa monitoring is used to assess efficacy but requires several doses to be administered. Thrombelastography assesses hypercoagulability and may have utility identifying high-risk patients for venous thromboembolism. The objective was to evaluate whether thrombelastography parameters could identify trauma patients requiring enoxaparin dose adjustment earlier than serum anti-Xa concentrations.
A single-center, retrospective medical record review evaluated patients admitted to a regional level I trauma center that received an admission thrombelastography and a dose of enoxaparin with a serum trough anti-Xa concentration drawn. Patients were divided into standard-dose or dose-adjusted enoxaparin. Venous thromboembolism incidence between groups and risk factors for enoxaparin dose adjustment and venous thromboembolism development were evaluated.
A total of 204 patients were included. Differences observed between groups included age (standard-dose enoxaparin, 48.5 [29.3–72] vs dose-adjusted enoxaparin, 38.5 [25–55.7] years; P = .005), admission creatinine clearance (standard-dose enoxaparin, 92.9 [67.4–113.4] vs dose-adjusted enoxaparin, 102.1 [83.8–129.2] mL/min; P = .017), and time to venous thromboembolism prophylaxis initiation (standard-dose enoxaparin, 23.8 [11.2–36.4] vs dose-adjusted enoxaparin, 34.5 [18.3–52.7] hours; P = .004). No differences in thrombelastography parameters or venous thromboembolism incidence were observed. No independent risk factors for enoxaparin dose adjustment were identified; however, risk assessment profile score > 10 was an independent risk factor for venous thromboembolism development.
No relationship between admission thrombelastography and need for enoxaparin dose adjustment in trauma patients was observed. As thrombelastography continues growing in clinical use, it is prudent to investigate other potential applications. Currently, thrombelastography should not be used to guide enoxaparin dosing.
Post-TBI splenectomy may exacerbate coagulopathy and platelet activation in a murine model
2020, Thrombosis Research
Traumatic brain injury (TBI) induces acute hypocoagulability, subacute hypercoagulability, and persistently elevated risk for thromboembolic events. Splenectomy is associated with increased mortality in patients with moderate or severe TBI. We hypothesized that the adverse effects of splenectomy in TBI patients may be secondary to the exacerbation of pathologic coagulation and platelet activation changes.
An established murine weight-drop TBI model was utilized and a splenectomy was performed immediately following TBI. Sham as well as TBI and splenectomy alone mice were used as injury controls. Mice were sacrificed for blood draws at 1, 6, and 24 h, as well as 7 days post-TBI. Viscoelastic coagulation parameters were assessed by rotational thromboelastometry (ROTEM) and platelet activation was measured by expression of P-selectin via flow cytometry analysis of platelet rich plasma samples.
At 6 h following injury, TBI/splenectomy demonstrated hypocoagulability with prolonged clot formation time (CFT) compared to TBI alone. By 24 h following injury, TBI/splenectomy and splenectomy mice were hypercoagulable with a shorter CFT, a higher alpha angle, and increased MCF, despite a lower percentage of platelet contribution to clot compared to TBI alone. However, only the TBI/splenectomy continued to display this hypercoagulable state at 7 days. While TBI/splenectomy had greater P-selectin expression at 1-h post-injury, TBI alone had significantly greater P-selectin expression at 24 h post-injury compared to TBI/splenectomy. Interestingly, P-selectin expression remained elevated only in TBI/splenectomy at 7 days post-injury.
Splenectomy following TBI exacerbates changes in the post-injury coagulation state. The combination of TBI and splenectomy induces an acute hypocoagulable state that could contribute to an increase in intracranial bleeding. Subacutely, the addition of splenectomy to TBI exacerbates post-injury hypercoagulability and induces persistent platelet activation. These polytrauma effects on coagulation may contribute to the increased mortality observed in patients with combined brain and splenic injuries.

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^*: Reprint requests: Frederick Rogers, MD, Fletcher Allen Health Care, Department of Surgery, 111 Colchester Ave, FL 466, Burlington, VT 05401.

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Clinical ReviewVenous thromboembolism in trauma patients: A review*

Abstract

Section snippets

Incidence

Pathophysiology

Risk factors for venous thromboembolism

Deep vein thrombosis

Standard prophylaxis

Investigational prophylaxis

Complications

Decision analysis on prophylactic measures after trauma

Future directions

Summary

Am J Surg

Surgery

Am J Surg

Lancet

Cardiovasc Surg

Ann Vasc Surg

J Am Coll Surg

J Vasc Interv Rad

Ann Vasc Surg

Chest

Blood

Blood

Lancet

The epidemiology of traumatic death: a population-based analysis

Arch Surg

Pulmonary embolism following trauma

Surg Gynecol Obstet

Venous thrombosis and pulmonary embolism: a clinicopathologic study in injured and burned patients

Br J Surg

An analysis of 950 fatal injuries

Surgery

Risk factors in pulmonary embolism

Surg Gynecol Obstet

Thromboembolism following multiple trauma

J Trauma

A prospective study of venous thromboembolism after major trauma

N Engl J Med

Pulmonary embolism in major trauma patients

J Trauma

“False negatives” and “false positives” in acute pulmonary embolism: a clinical-postmortem comparison

Cardiologia

Gesammele abhandlungen zue wissenschaft-licher medizin, von meidinger sohn

Franfur-ann-Main

Coagulation changes in elective surgery and trauma

Ann Surg

Alterations in coagulation and fibrinolytic system in acute trauma

J Trauma

D-dimer levels correlate with pathologic thrombosis in trauma patients

J Trauma

Prophylactic vena cava filter insertion in severely injured trauma patients. Indicators and preliminary results

J Trauma

Post trauma thromboembolism prophylaxis

J Trauma

Prevention of venous thromboembolism after injury: an evidence-based report—part II: analysis of risk factors and evaluation of the role of vena cava filters

J Trauma

Deep vein thrombosis and pulmonary emboli in neurosurgical patients: a review

J Neurosurgery

Roentgen diagnosis of venous thrombosis in the leg

Arch Surg

Contrast venography of the leg: diagnostic efficacy, tolerance, and complication rates with ionic and nonionic contrast media

Radiology

Posttraumatic venous thrombosis

Arch Surg

Systematic lower limb phlebography in acute spinal cord injury in 147 patients

Paraplegia

The detection and management of proximal deep venous thrombosis in patients with acute acetabular fractures: a follow-up report

J Ortho Trauma

Detection of deep-vein thrombosis by real-time B-mode ultrasonography

N Engl J Med

Diagnosis of deep vein thrombosis in asymptomatic high-risk patients

Haemostasis

Prospective ultrasound evaluation of venous thrombosis in high-risk trauma patients

J Trauma

Femoral catheters and deep venous thrombosis: a prospective evaluation with venous duplex sonography

J Trauma

Prevention of venous thromboembolism in trauma patients

J Trauma

Clinical Review
Venous thromboembolism in trauma patients: A review*