S P E C I A L

F O C U S

Trauma-Orthopaedics
Current concepts in deep vein thrombosis and
pulmonary embolism after trauma
Nathan A. Wigner and Derek J. Donegan

ABSTRACT
Venous thromboembolism (VTE), which includes deep venous
thrombosis (DVT) and pulmonary embolism (PE), is a leading
and potentially preventable cause of morbidity and mortality in
all hospitalized patients and particularly in the setting of trauma.
Guidelines for VTE prophylaxis have been created for elective
orthopaedic surgery procedures but little cohesive evidence
exists to guide VTE prophylaxis for trauma patients. The most
important outcome of any VTE prophylaxis strategy is its effect
on mortality from thrombosis and bleeding. Unfortunately,
current evidence suggests little to no effect of our interventions.
Although deemed a never event by entities such as Medicare,
population-based data have not shown a reduction in either the
incidence or mortality from VTE in hospitalized patients. The
purpose of this review article is to present the current literature
on VTE prophylaxis, treatment, and controversies in orthopaedic
trauma.
Key Words
DVT, PE, deep vein thrombosis, pulmonary embolism,
orthopaedic trauma

INTRODUCTION

enous thromboembolism (VTE) is a principal cause

of death in all trauma patients. It is estimated that
sudden death is the initial presentation in 25% of
patients with pulmonary embolism (PE); which, in part,
makes PE one of the most common causes of preventable
hospital-related death.1,2 As such, many national organizations have prioritized VTE prevention as a major patient
safety initiative and recommend VTE risk assessment and
explicit policy developments to prevent VTE. The purpose of
this review article is to present the current literature on VTE
prophylaxis, treatment, and controversies in orthopaedic
trauma.

SCOPE OF THE PROBLEM

Venous thromboembolism (VTE) is a major health care
problem, with an incidence of 1 per 1000 person-years
accounting for approximately 5% to 10% of US inpatient
hospitalized deaths annually. This translates to more deaths
each year from VTE than breast cancer, AIDS, and traffic
accidents combined.1 Although pharmacologic VTE prophylaxis has been shown to reduce the risk of VTE by as
much as 75% in surgical patients,3 population-based data
have not shown a reduction in either the incidence of
clinically significant VTE or the number of deaths from PE in
hospitalized patients.2
Although VTE is arguably the most common preventable
cause of mortality and morbidity in hospitalized patients,
studies have shown that VTE prophylaxis remains underutilized in the United States. In a recent retrospective review
by Schleyer et al.4 of 1555 medical and surgical acute and
intensive care patients at 33 US academic medical centers,
adherence to VTE prophylaxis for at-risk patients was
significantly lower than expected. In total they found that
compliance with VTE prophylaxis guidelines was only 48%
overall with medical and surgical intensive care patients
being 59% and 41%, respectively. As such VTE prevention
has become a patient safety priority as underscored by the
Surgeon Generals Call to Action to Prevent Deep Vein
Thrombosis and Pulmonary Embolism in 2008.1 In addition
the Agency for Healthcare Research and Quality (AHRQ)
now ranks VTE prophylaxis as among the most important
interventions to improve patient safety.5 Despite many
national organizations prioritizing VTE prevention as a
critical patient safety initiative there has been little
consensus on the development of effective and safe risk
assessment strategies not to mention policy-supported,
evidence-substantiated VTE prophylaxis protocols for trauma patients.

PATHOPHYSIOLOGY
Department of Orthopaedic Surgery, University of Pennsylvania Health
System, Philadelphia, PA
Financial Disclosure: The authors report no conflicts of interest.
Correspondence to Derek J. Donegan, MD, Department of Orthopaedic
Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street,
2 Silverstein Building, Philadelphia, PA 19104
Tel: (215) 662-3340; fax: (215) 349-5890;
e-mail: derek.donegan@uphs.upenn.edu
1940-7041 r 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

208

Current Orthopaedic Practice

It is well known that orthopaedic trauma patients are at

high risk for clinically significant VTE (Figure 1). This is
supported by numerous studies identifying injury-specific
risk factors, such as spinal cord injury, pelvic fractures, lower
extremity fractures, high injury severity, and longer ventilation times, that place patients at increased risk for
symptomatic VTE.6 Major trauma precipitates one if not
all three of Virchows triad of factors that predispose
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Critical to efficient management of PE in orthopaedic

patients is the effective stratification of patient clinical risk.
For suspected PE, the Wells Criteria is the most commonly
used clinical model for determining a patients pretest
probability of PE while hospitalized. Although a cornerstone
in the classic teaching of VTE management since its
development in the mid-90s, recent data suggests that the
Wells Criteria is limited in predicting PE risk in orthopaedic
trauma patients. Recently, Young et al.11 examined the
utility of the Wells score in predicting PE in 6854
orthopaedic trauma patients.11 Of 169 (2.74%) patients
who underwent CTPA for suspected PE, only 27 patients
(16%) had a positive PE diagnosis. More importantly, they
showed that no significant predictive relationship was
found between the traditional or the alternative Wells score
and PE diagnosis in orthopaedic trauma patients, P 0.726
and P 0.601, respectively.

COMPLICATIONS

FIGURE 1. (A and B) Representative inpatient radiographs of a multitrauma patient.

thrombus formation: hypercoagulability, endothelial injury,

and venous stasis Conventional wisdom teaches that
symptomatic VTE, namely PE, arises as a result of DVT in
the pelvis and lower extremity and ultimately embolizes to
the lungs, with a majority of these occurring after 7 days.
This not only suggests a temporal and causal relationship
between the two but, more importantly, represents an
opportunity to intervene and prevent PE.

DIAGNOSIS
The diagnosis of DVT and PE remains a challenge due to the
variability in presentation. It often is subtle, atypical, or
even silent. In a review of 695 patients, Kim et al.7 found a
27.8% rate of positive computed tomographic pulmonary
angiography (CTPA) results for PE in postoperative orthopaedic patients. In addition, current literature has failed to
show that despite the diagnostic utility of sequential duplex
ultrasound screening, its use does not decrease the risk of PE
in orthopaedic trauma.8 In fact recent American Academy of
Orthopaedic Surgery (AAOS) VTE guidelines strongly recommend against routine postoperative duplex ultrasonography screening in orthopaedic patients. Notably this is the
only strong recommendation by the AAOS.9 This also is
echoed by the Orthopaedic Trauma Association (OTA) in the
most recent OTA Evidence-Based Medicine (EBM) Committee Guidelines, recommending that duplex ultrasonography
should not be used to screen asymptomatic orthopaedic
trauma patients.10

Although PE can lead to complications and death as a result

of the disease process itself, the treatment of patients
diagnosed with PE is not trivial and carries iatrogenic risks
stemming from the requirement of immediate long-term
anticoagulation. There is concern that the increased sensitivity of CTPA has led to over-diagnosis of patients with
nonfatal disease who do not benefit from intervention.
Wiener et al.12 looked at US trends before and after the
advent of CTPA and reported an 81% increased incidence of
PE after CTPA and a 71% increase in complications from
anticoagulation.12 In regards to orthopaedic trauma patients, complications of anticoagulation, such as the risk of
surgical site bleeding have been shown to be significant not
to mention equally as common regardless of whether a
patient is low or high risk.13 In addition to the risk of
iatrogenic bleeding, DApuzzo et al.14 showed that the
diagnosis and treatment of PE doubled patient length of
stay and increased total hospital charges by approximately
70% in orthopaedic surgical patients. Despite increased use
of CTPA and better detection of PE in orthopaedic patients,
many studies have shown little to no improvement in PEassociated mortality.15

DVT/PE DISCORDANCE
Interestingly, many patients with a confirmed PE completely
lack evidence of peripheral DVT. This seemingly low
coexistence of PE and DVT after trauma has led some
investigators to question the classic dogma that PE arises
from peripheral thrombosis. In the largest analysis of
888,652 patients to date by Knudson et al.,16 9398 had
DVT, 3738 had PE, and only 20% (n 801) of those with PE
had an identifiable DVT.16 This finding has been supported
by a number of studies showing that trauma patients
diagnosed with PE rarely had concurrent DVT.
In a recent multicenter prospective study of 1822 patients
with severe blunt trauma, Brakenridge et al.17 showed that
only nine (12.3%) of 73 patients with a PE also had DVT.
Similarly, in a study by Velmahos et al.18 of 247 trauma
patients who underwent CTPA for suspected PE, only 15% of

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those found to have a PE also had a DVT of the pelvic and

proximal veins on CT venography.18 Although the argument can be made that the lack of DVT in patients
diagnosed with PE merely represents embolization of the
entire clot, cadaver studies have proven that generally only
part of the clot embolizes and significant clot burden
remains adherent to the peripheral endothelium.19
The conventional wisdom is further brought into question
because recent trauma literature has demonstrated that a
significant proportion of PE are identified early during a
patients clinical course, with many being diagnosed within
the first 24 h of hospitalization. In addition, a study
published by Benns et al.20 showed that injury-related early
PE has different clinical risk factors than other forms of VTE.
They demonstrated that only lower extremity fracture was
an independent risk factor for early PE and that differing risk
factor profiles, not to mention unique temporal patterns,
suggest that early versus late PE may represent different
clinical entities or at least distinct pathophysiologic mechanisms.20 However, it is unclear whether early PE arises from
an unknown mechanism either de novo to the pulmonary
circulation or otherwise or how lower extremity trauma
truly contributes to its development.

PROPHYLAXIS FOR VTE IN TRAUMA PATIENTS

VTE prophylaxis in trauma patients poses a unique challenge because the factors leading to thrombosis likely
develop immediately after the injury, namely before the
administration of any type of prophylactic therapy is
possible. This dilemma is compounded by the fact that
contraindications arising from associated injuries often limit
the potential options for prophylaxis in these patients.
Thus, the use of early pharmacologic thromboprophylaxis
in patients considered at increased risk of bleeding remains
controversial. A recent randomized control study by Phelan
et al.,21 assessing early versus delayed pharmacologic
thromboprophylaxis in patients with traumatic brain injury
(TBI) showed that early use did not place patients at
increased risk of intracranial bleeding when compared with
placebo.
Nonpharmacologic prophylaxis includes inferior vena
cava (IVC) filters and mechanical devices such as antiembolic
stockings and intermittent pneumatic compression devices
(IPCD). Generally nonpharmacologic modalities, such as
IPCD and IVC filters, are recommended in patients in whom
anticoagulation is contraindicated because of increased risk
of bleeding. Despite their widespread use, much of the
current literature on mechanical prophylaxis has not shown
their use in orthopaedic patients to be beneficial in
symptomatic DVT or PE prevention when compared with
no prophylaxis.22,23 In a recent systematic review and metaanalysis on prophylactic IVC filter use in trauma patients,
Haut et al.24 were unable to show that prophylactic IVC filter
placement significantly affected the incidence of PE, fatal PE,
or mortality in hospitalized trauma patients.24
In the absence of pharmacologic prophylaxis, DVT and PE
rates exceed 50% and 10%, respectively. In fact, fatal PE is
the third leading cause of death in those who survive the
first day.25 Pharmacologic prophylaxis includes low dose

unfractionated heparin (UFH); low-molecular weight heparins (LMWH), such as enoxaparin and dalteparin; aspirin,
and warfarin, along with newer classes of antithrombotic
agents. While the evidence for nonpharmacologic prophylaxis is lacking, a recent systematic review showed that
pharmacologic prophylaxis significantly reduces the risk of
DVT in hospitalized patients.26 Ultimately, this finding
raises the question: are asymptomatic end points such as
DVT effective surrogates for patient-important outcomes for
symptomatic DVT and PE in orthopaedic patients? Despite
the effect of prophylaxis on DVT, many studies have been
unable to show that thromboprophylaxis reduces risk for PE
or VTE-associated mortality in trauma patients or those
having elective orthopaedic surgery.26,27
Taking the above into account, the American College of
Chest Physicians (ACCP) and OTA EBM Committee have
recently published guidelines for pharmacologic prevention
of VTE in trauma patients. According to the latest ACCP
guidelines, the ACCP recommends the use of LMWH for
patients with major trauma as soon as it is considered safe to
do so. If deemed safe, the ACCP recommends starting
LMWH either 12 h or more preoperatively or 12 h or more
postoperatively. This is echoed by the latest OTA guidelines
that recommend initiating LMWH therapy (enoxaparin
30 mg, twice a day) and IPCD within 24 h unless contraindications are present such as TBI, solid organ injury less
than 24 h, ongoing hemorrhage, or the use of a concurrent
epidural catheter. With regard to pharmacologic duration, the
ACCP recommends 10 to 14 days of pharmacologic prophylaxis in the setting of hip fractures and 35 days for other major
orthopaedic surgery. The OTA was unable to find reliable
evidence to recommend a specific duration of pharmacologic
strategies; rather this should be shared decision between
physicians and patients on an individual basis.9,28
It is clear that VTE is one of the major problems of trauma
patients. Unfortunately, there are neither sufficient highquality studies nor consensus to provide the optimal balance
between safe and efficient prophylaxis in these patients. To
this end, our institution has developed our own risk-based
VTE practice management protocol for trauma patients in
collaboration with General Surgery Trauma (Figure 2).
This current protocol is based on the literature suggesting
that trauma patients who develop VTE tend to be more
severely injured. The protocol stratifies patients into
moderate risk, high risk, and very high or refractory risk
patients. Once stratified, the algorithm suggests the use of
IPCD and LMWH. Additionally, our protocol uses screening
duplex ultrasound in high and very high-risk patients.
While this is the current protocol being used at our
institution, the pathway is routinely reevaluated and
changed based on emerging literature.

CONCLUSION
VTE, which includes DVT and PE, is a leading and
potentially preventable cause of morbidity and mortality
in all hospitalized patients, especially those with trauma. At
this time, there is little consensus for the optimal prophylactic regimen. Fortunately, evidence-based medicine groups

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Current Orthopaedic Practice

FIGURE 2. Hospital of the University of Pennsylvania Deep Venous Thrombosis Prophylaxis Clinical Practice Guidelines. aBased on Eastern Association for
the Surgery of Trauma (EAST) 1998 guidelines and 2001 update. bRefractory risk factors based on Baldwin et al.6 study. Low-molecular weight heparin
(LMWH) is used unless contraindicated. AIS, Abbreviated Injury Score; CHF, congestive heart failure; DVT, deep vein thrombosis; GCS, Glasgow Coma
Scale; IVC, inferior vena cava; ISS, Injury Severity Score; LE, lower extremity; PE, pulmonary embolism; SCD, sequential compression devices. (Reprinted
with permission from Baldwin et al.6).

have recently been developed to help answer this question

and allow for best practices to be initiated.

2.

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