Review Article

Venous Thromboembolism
Prophylaxis in Spine Surgery

Abstract
Christopher K. Kepler, MD, MBA Venous thromboembolism (VTE) is a source of morbidity and mortality
James McKenzie, MD in patients undergoing orthopaedic surgery. A substantial body of
literature supports the use of VTE prophylactic agents in patients
Tyler Kreitz, MD
undergoing lower extremity surgery. Treatment options include early
Alexander Vaccaro, MD, PhD, mobilization, mechanical prophylaxis via pneumatic compression
MBA
devices, pharmacologic agents, and venous filters. No consensus has
been established regarding utilization or timing of VTE prophylaxis
measures after spine surgery. The risk of VTE in patients undergoing
spine surgery is not well characterized and varies substantially by the
procedure and degree of neurologic compromise. In addition, the risk
of clinically notable VTE must be weighed against the risk of
postoperative bleeding and epidural hematoma after spine surgery.
A standardized approach to VTE prophylaxis in patients undergoing
spine surgery must take into account the available studies of risk
factors, choice of prophylactic agents, and timing of prophylaxis.

V enous thromboembolism (VTE)

From the Department of Orthopaedic
Surgery, Thomas Jefferson University
Hospitals (Dr. McKenzie), and
Rothman Institute Orthopedics,
Philadelphia, PA (Dr. Kepler,
Dr. Kreitz, and Dr. Vaccaro).
J Am Acad Orthop Surg 2018;0:1-12
DOI: 10.5435/JAAOS-D-17-00561
Copyright 2018 by the American
Academy of Orthopaedic Surgeons.
is the most common preventable
cause of hospital mortality and the
third most common cause of hospital-
associated death.1 Surgical patients
are at increased risk of VTE because
of induced prothrombotic states,
perioperative venous stasis, and re-
duced mobility. Early mobilization
of patients may be delayed because
of postoperative pain and neurologic
compromise, increasing the risk of
VTE.2 The incidence of VTE after
spine surgery is poorly defined, with
estimates ranging from 0.3% to 31%,
which suggests substantial variability
according to comorbidities, includ-
ing the degree of neurologic com-
promise.3 No consensus has been
established regarding perioperative
VTE prophylaxis in patients under-
going spine surgery. The risk of clin-
ically notable VTE must be weighed
against the risk of postoperative
bleeding and epidural hematoma.4 In
the discussion of perioperative VTE
chemoprophylaxis for spine surgery
patients, Bono et al,5 representing
the 2009 North American Spine So-
ciety work group, found insufficient
evidence to definitively recommend
the routine use of chemoprophylaxis
in patients undergoing elective spine
surgery.
Prevalence and Risk
Factors
Perioperative VTE risk in patients
undergoing spine surgery can be
stratified on the basis of the anatomic
segment (ie, cervical versus tho-
racolumbar), surgical approach (ie,
posterior, anterior, or combined),
or the degree of neurologic compro-
mise (Table 1). Oglesby et al6 evalu-
ated the incidence of VTE after
273,396 cervical procedures from the
National Inpatient Sample database
from 2002 to 2009. Risk factors were

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Venous Thromboembolism Prophylaxis in Spine Surgery

stratified by approach, patient demo-
graphics, and comorbidities. Overall,
the rate of VTE was 5.0 per 1,000
procedures (0.5%), with patients
experiencing deep vein thrombosis
(DVT) or pulmonary embolism having
an average length of stay of 22.6 days
and a 10-fold increase in mortality
compared with those without VTE,
whose length of stay averaged 4.3
days. Patients undergoing posterior
cervical fusion had the highest rate of
VTE (13.4 per 1,000 patients; odds
ratio [OR], 2.3), with increased risk in
men (OR, 1.8) and in patients with
postoperative anemia (OR, 4.8), elec-
trolyte and fluid disturbances (OR,
2.2), and/or pulmonary vascular
pathology (OR, 3.70). Oglesby et al6
concluded that many VTE risk factors
after cervical surgery mirror the overall
risk factors for perioperative compli-
cations, including comorbidities,
immobility, and hypercoagulability.
In another large, retrospective data-
base review, Sebastian et al7 evaluated
the incidence of VTE in 43,777
patients undergoing thoracolumbar
surgery from 2005 to 2012 using
the American College of Surgeons
National Surgical Quality Improve-
ment Program database. They found
low rates of DVT (0.7%) and pul-
monary embolism (0.5%) in all
patients undergoing thoracolumbar
surgery. The increased incidence was
statistically significant for patients
undergoing corpectomy, with rates of
3.8% and 1.7% for DVT and pul-
monary embolism, respectively, in
these patients. In addition, hospital
length of stay .6 days (OR, 4.07),
diagnosis of malignancy (OR, 1.77),
paraplegia (OR, 1.76), albumin ,3
(OR, 1.73), surgical time .193
minutes (OR, 1.43), body mass index
(BMI) .40 (OR, 1.49), and American
Society of Anesthesiologists class $4
(OR, 1.54) were all independent risk
factors for VTE after thoracolumbar
surgery. Patients with a length of stay
,3 days had a reduced incidence of
VTE (OR, 0.43), suggesting a benefit
of early mobilization and expedited
rehabilitation. Both retrospective da-
tabase studies demonstrated a low
incidence of VTE (0.5% to 0.7%).
Patients with prolonged surgical times,
neurologic compromise, delayed mo-
bilization, and comorbidities such as
malnutrition and malignancy may be
at increased risk of VTE.
Anterior lumbar procedures may
place patients at additional risk of VTE.
Ballard et al8 retrospectively evalu-
ated 617 patients who underwent
procedures with an anterior thoracic
and/or thoracolumbar approach by
a single vascular surgeon and found
a perioperative DVT rate of 2%. The
risk increased markedly in patients
with BMI .30 (P , 0.018) and
those undergoing multilevel (.2)
exposures (P , 0.001). The authors
concluded that although the incidence
of VTE is greater with the anterior
thoracolumbar approach than with
the posterior approach, anterior
thoracolumbar surgery has a low
overall risk of VTE and may be safely
performed. An earlier, more aggres-
sive VTE prophylactic regimen may be
considered in patients undergoing
anterior thoracolumbar approaches.
A patient’s risk of perioperative
VTE may also be stratified according
to comorbidities and history of
thrombotic events. A 2016 meta-
analysis of 12 retrospective studies
by Wang et al9 reported a 2% risk of
postoperative VTE among 34,597
patients undergoing spine surgery.
The authors of the study found that
preoperative ambulatory disability
(OR, 4.80), diabetes (OR, 2.12), and
hypertension (OR, 1.59) were the
major independent risk factors for
VTE after spine surgery. Surgical time
(,2 versus .2 hours), BMI, smok-
ing, fusion procedure, and age were
not associated with an increased risk
of perioperative VTE.9 An evalua-
tion of 22,434 spine surgeries sam-
pled from the American College of
Surgeons National Surgical Quality
Improvement Program database
from 2006 to 2010 demonstrated a
1.1% rate of VTE (ie, 0.8% for DVT
and 0.3% for pulmonary embolism).
Nine patient-specific risk factors
were associated with VTE, including
hypertension (OR, 2.08), dependent
functional status (OR, 4.34), malig-
nancy (OR, 6.83), inpatient status
(OR, 7.13), paraplegia (OR, 3.74),
and quadriplegia (OR, 5.63).10 Both
retrospective studies identified patients
with reduced mobility and functional
status as being at higher risk of peri-
operative VTE after spine surgery,
suggesting a benefit of a more
aggressive VTE prophylaxis regi-
men in this population.
Patients with spinal cord injury (SCI)
may be at higher risk of VTE, com-
pared with other patients, because of
immobility, neurologic disability, and
other injuries. Matsumoto et al11 per-
formed a prospective study of 29

Dr. Kepler or an immediate family member has received research or institutional support from Medtronic, Pfizer, and Zimmer Biomet.
Dr. Vaccaro or an immediate family member has received royalties from Aesculap and Globus Medical; serves as a paid consultant to Atlas
Spine, Gerson Lehrman Group, Guidepoint Global, HealthpointCapital, InVivo Therapeutics, MedaCorp, Medtronic, NuVasive, and Stryker;
has stock or stock options held in Advanced Spinal Intellectual Properties, Atlas Spine, Avaz Surgical, Bonovo Orthopedics, Computational
Biodynamics, Cytonics, Dimension Orthotics, ElectroCore, Flagship Surgical, FlowPharma, Gamma Spine, Globus Medical, Innovative
Surgical Designs, Insight Therapeutics, NuVasive, Paradigm Spine, Parvizi Surgical Innovations, Prime Surgeons, Progressive Spinal
Technologies, Replication Medical, Spine Medica, Spine Wave, Spineology, Stout Medical, Vertiflex, and Vexim; and serves as a board
member, owner, officer, or committee member of AOSpine and Flagship Surgical. Neither of the following authors nor any immediate family
member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this article: Dr. McKenzie and Dr. Kreitz.

2 Journal of the American Academy of Orthopaedic Surgeons

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 Christopher K. Kepler, MD, MBA, et al

Table 1
Studies Determining Perioperative VTE Risk
Study Design No. of Level of
Study (Procedure) Patients Intervention Results Evidence

Oglesby Retrospective 273,396 Analysis of incidence, Posterior cervical fusion had IV

et al6 database review risk factors, and higher VTE incidence than
(anterior/posterior mortality for DVT/ anterior cervical fusion had.
cervical spine pulmonary embolism Male sex, teaching-hospital
decompression status, pulmonary
and/or fusion) circulation, and electrolyte
disorders were associated
with increased VTE risk.
Sebastian Retrospective 43,777 Analysis of incidence 0.7% DVT rate and 0.5% IV
et al7 database review and timing of DVT/ pulmonary embolism rate
(thoracolumbar pulmonary embolism within 30 d of surgery.
decompression and multivariate Corpectomy had highest risk
and/or fusion) analysis of DVT/ of DVT/pulmonary
pulmonary embolism embolism. BMI . 40,
risk factors paraplegia, American
Society of Anesthesiologists
class .4, length of stay .7
d, and other factors were
associated with increased
VTE risk.
Ballard Retrospective 617 Analysis of DVT/ Two percent incidence of DVT III
et al8 single-surgeon pulmonary embolism, overall. Substantial increase
case series wound complications, in risk of DVT in patients with
(anterior and hospital obese BMI or multilevel disk
thoracolumbar readmission after exposure.
spine exposure) anterior
thoracolumbar surgery
Wang et al9 Meta-analysis 34,597 Pooled analysis of 12 Two percent incidence of VTE I
(degenerative studies on risk factors overall. Patients with
cervical/ for DVT/pulmonary preoperative ambulatory
thoracolumbar embolism after dysfunction, hypertension,
spine degenerative spine lumbar surgery, and/or
decompression/ surgery diabetes had a markedly
fusion) increased risk of VTE.
Piper et al10 Retrospective 22,434 Analysis of clinical 1.1% rate of VTE (DVT, 0.8%; III
database review factors associated with pulmonary embolism, 0.3%).
(unspecified spinal VTE in spine surgery Preoperative risk factors
surgery) patients included hypertension,
dependent functional status,
malignancy, inpatient status,
paraplegia, and
quadriplegia.
Matsumoto Prospective cross- 29 (18 cervical Routine D-dimer and 41.3% rate of VTE after III
et al11 sectional study and 10 postoperative surgery at a median time of
(acute SCI) thoracolumbar) ultrasonographic postoperative day 7.5.
screening for DVT Higher risk of postoperative
after surgery for acute VTE with more severe
SCI without paralysis (66.3% of patients
preoperative with VTE had severity of A or
anticoagulation B on the American Spinal
Cord Association
Impairment Scale).
(continued )
BMI = body mass index, DVT = deep vein thrombosis, SCI = spinal cord injury, VTE = venous thromboembolism

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Venous Thromboembolism Prophylaxis in Spine Surgery
Table 1 (continued )
Studies Determining Perioperative VTE Risk
Study Design
Study (Procedure)
Agarwal Prospective
and randomized
Mathur12 controlled study
(acute SCI; injury
type not specified)
BMI = body mass index, DVT = deep vein thrombosis, SCI = spinal cord injury, VTE = venous thromboembolism
patients with acute SCI (ie, 19 cervical
and 10 thoracolumbar) who under-
went surgery within 24 hours of injury
without anticoagulant therapy. They
routinely screened for postoperative
DVT via D-dimer testing, ultraso-
nography, and physical examination
on postoperative days 1, 3, 7, 14, and
28. In this study, 12 patients (41.4%)
had DVT developed at a median time
of postoperative day 7.5. At the time
of presentation, 66% of these patients
were classified as A or B on the
American Spinal Cord Association
Impairment Scale, measuring the
severity of paralysis. All the DVTs
were distal to the popliteal fossa. The
authors concluded that acute SCI
with paralysis may warrant post-
operative VTE screening. Agarwal
and Mathur12 performed a pro-
spective randomized controlled trial
of 297 patients with acute SCI
undergoing nonsurgical treatment,
with 166 patients receiving 5,000 IU
of unfractionated low-dose heparin
starting at the time of randomiza-
tion (on average 8 days after injury)
for 90 days and 131 patients not
receiving anticoagulation. Both
populations received physical ther-
apy. Screening venous Doppler
ultrasonography was performed in
patients demonstrating an increase
in calf girth of 2 cm with concomi-
tant fever. The incidence of DVT
had no significant difference between
4 Journal of the American Academy of Orthopaedic Surgeons
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No. of
Patients Intervention
297 Patients with acute SCI Three patients (1.8%) in the
randomized to receive study group and four patients
5,000 IU of low-dose
heparin for 90 d versus had DVT, which was not a
no anticoagulation,
with VTE screening
based on symptoms of need to be individualized on
DVT
groups, with three (1.8%) in the
study group and four (3.0%) in
the experimental group (P . 0.05).
The authors concluded that VTE
screening may be necessary only in
patients with clinical symptoms of
VTE and may be population depen-
dent.12 Higher-level studies with
standardized protocols are needed to
determine the utility of VTE screening
in patients with acute SCI.
Postoperative Epidural
Hematoma Risk
The risk of a clinically significant
VTE event must be weighed against
the risk of postoperative hemorrhage
associated with prophylactic anti-
coagulation. In a systematic level I
review of 16 studies, Glotzbecker
et al13 reported a 0.2% overall inci-
dence of postoperative epidural
hematoma. The incidence ranged from
zero to 0.7%. Six of the 16 studies
included chemical VTE prophylaxis
consisting of low-molecular-weight
heparin (LMWH) or unfractionated
heparin (UFH). Ten studies used no
chemical VTE prophylactic agent. No
notable difference in epidural hema-
toma incidence was found among the
studies.13 The authors concluded
that epidural hematoma is a rare yet
devastating complication that requires
further study to determine risk fac-
Level of
Results Evidence
II
(3.0%) in the control group
statistically significant
difference. Screening may
a case-by-case basis.
tors. Schroeder et al14 performed a
multicenter retrospective level III
study including 16,582 patients from
23 institutions undergoing cervical
spine surgery. They found a 0.090%
incidence of epidural hematoma. All
patients with epidural hematoma
had neurologic deficit, which per-
sisted in 33% of these patients at
6-week follow-up even with prompt
diagnosis and treatment.14 Both stud-
ies had a low incidence (,1.0%) of
epidural hematoma, with substantial
morbidity occurring in patients with
the complication.
Mechanical Prophylaxis
External Compression
Devices
Intermittent pneumatic compression
(IPC) and sequential compression
devices (SCDs) are effective nonin-
vasive methods of postoperative VTE
prophylaxis. These devices provide
intermittent circumferential compres-
sion to the patient’s leg, improving
venous blood flow in the lower
extremity, and their use and efficacy
after total joint arthroplasty have
been well documented.15 However,
the efficacy of these devices in VTE
prevention after spine surgery has
not been sufficiently described. In a
prospective efficacy assessment of
100 single-level anterior cervical

diskectomy and fusions and 100
multilevel anteroposterior cervical
decompression procedures using IPC
with postoperative Doppler ultra-
sonography, Epstein16 reported VTE
rates of 1% and 7%, respectively,
with a 2% rate of pulmonary embo-
lism in the latter group. This incidence
of VTE is comparable to previously
cited rates of VTE in studies using
LMWH.16 This study by Epstein16
was limited by the lack of direct
comparison with chemical VTE
prophylaxis and the lack of a con-
trol group. In addition, all patients
were routinely screened regardless
of symptoms. Routine screening for
DVT is not recommended because
the clinical significance of DVTs
distal to the popliteal fossa has
come into question, particularly in
the orthopaedic literature.
A different retrospective study by
Epstein,17 which included 139 pa-
tients undergoing posterior lam-
inectomy and fusion, demonstrated a
DVT rate of 2% and a pulmonary
embolism rate of 0.7%, which is
comparable to the incidences asso-
ciated with LMWH regimens. Ferree
and Wright18 compared the efficacy
of SCDs with that of IPC in the
prevention of DVT in 185 patients
undergoing posterior lumbar decom-
pression and fusion. All patients
underwent postoperative venous
duplex ultrasonography at 7 days
postoperatively regardless of symp-
toms. The use of SCDs demonstrated a
significant reduction in postoperative
DVT compared with the use of elastic
compression stockings (P , 0.05). The
four DVTs found were asymptomatic
and were in the elastic compression
stocking group. Early mobilization
was encouraged for both groups.18
Despite the lack of high-quality
studies demonstrating the efficacy of
external compression devices, specif-
ically in spine patients, their routine
use should be included in all spine
postoperative protocols. External
compression devices are minimally
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invasive, are easy to apply, and may
reduce the risk of VTE events by
preventing venous stasis (Table 2).
Inferior Vena Cava Filters
An inferior vena cava (IVC) filter is
an endovascular device designed to
physically block substantial throm-
bosis from reaching the pulmonary
vasculature. Placement requires an
invasive endovascular procedure.
These devices have been used in
patients undergoing spine surgery
who demonstrate preoperative DVT,
who have a contraindication for an-
ticoagulation, or who are at high risk
of VTE. Within these parameters,
IVC filters have shown considerable
efficacy in reducing the risk of pul-
monary embolism. Leon et al19
retrospectively reviewed 74 patients
identified as being at high risk of
VTE who received IVC filters before
posterior thoracolumbar surgery.
Patients were considered to be at
high risk of VTE if they had a history
of VTE, malignancy, or thrombo-
philia; underwent a staged procedure;
were bedridden for .2 weeks pre-
operatively; and/or had an estimated
anesthesia time of .8 hours. Most of
the patients included in the study had
two to four high-risk comorbidities
documented before surgery. The
authors found 27 DVTs (31%),
with 18 (24.3%) being proximal to
the popliteal fossa, and one pul-
monary embolism (1.3%) during
routine weekly imaging with color
duplex Doppler ultrasonography of
the bilateral lower extremities in
all patients. Only one complication
(1.3%) related to DVT prophylaxis
(failed IVC filter deployment) occurred
during the study. The authors con-
cluded that in a population at high risk
of VTE, IVC filters were associated
with a very low rate of pulmonary
embolism. However, no control group
was used in the study.19
A comparable case series of 12
patients undergoing multilevel
Christopher K. Kepler, MD, MBA, et al
thoracolumbar surgery who were at
elevated risk of VTE or had a contra-
indication for medical anticoagulation
demonstrated that two patients (17%)
had entrapped thrombi on retrieval of
their IVC filters postoperatively.20 Ten
patients (83%) had their IVC filters
successfully retrieved with no compli-
cations or pulmonary embolism events
at follow-up. The authors concluded
that pulmonary embolism occurs in
this high-risk population and that IVC
filters can protect against pulmonary
embolism and be safely removed if
necessary.20 In both studies, the only
methods of perioperative prophylaxis
were the use of IPC devices and early
ambulation when possible. In patients
at high risk of VTE who are under-
going major spine surgery, IVC filters
may be a useful adjunct for the
prevention of pulmonary embolism
(Table 2).
Early Mobilization
Early inpatient postoperative mobi-
lization, with physical therapy eval-
uation, is a safe and effective
modality to reduce the risk of VTE
after surgery.2,7 Early mobilization
also is associated with reduced hos-
pital length of stay, reduced risk of
pneumonia, and improved func-
tional outcomes.21
Pharmacologic
Prophylaxis
Subcutaneous Heparin
Delivered subcutaneously, UFH
binds to and activates antithrombin
III, resulting in inhibition of throm-
bin, factor Xa, and other proteases
in the clotting cascade. Few studies
have evaluated the efficacy of and
risks associated with UFH use after
spine surgery. A 2014 retrospective
review by Cox et al3 compared
short- and long-term outcomes of
patients undergoing spine surgery
using a VTE protocol of SCDs and
5
Venous Thromboembolism Prophylaxis in Spine Surgery

Table 2
Studies Evaluating Mechanical VTE Prophylaxis
Study Design No. of Level of
Study (Procedure) Patients Intervention Results Evidence

Epstein16 Prospective cohort 200 (100 in Prospective efficacy analysis One DVT and no pulmonary
(single-level ACDF each
versus multilevel AP cohort)
CDF)
Epstein17 Prospective case
series (multilevel
lumbar
decompression/
fusion)
Ferree and Prospective cohort
Wright18 study (posterior
lumbar laminectomy
and/or fusion)
Leon et al19 Retrospective case
series (complex and/
or staged spinal
surgery)
Dazley Retrospective clinical
et al20 case series (major
spinal surgery)
II
of IPCs for VTE prevention embolism in the single-level
in 100 patients undergoing ACDF group. Seven DVTs
ACDF versus 100 patients in the AP CDF group, with
undergoing AP CDF, with two pulmonary embolisms.
postoperative The effectiveness of IPCs
ultrasonographic was comparable to that of
evaluation chemical prophylaxis, with
no risk of bleeding.
139 Prospective analysis of IPCs Four DVTs and one III
in prevention of VTE with pulmonary embolism (2.8%
postoperative and 0.7%, respectively)
ultrasonographic comparable to VTE rates
evaluation with chemoprophylaxis
185 Comparison of IPC (111 Four DVTs in the elastic III
patients) versus elastic compression stockings
compression stockings (84 group (2% incidence); none
patients) for VTE in IPC group (P , 0.05). No
prevention with pulmonary embolism in
postoperative either group. No
ultrasonographic statistically significant
evaluation difference in the rate of
DVT based on the surgery
type.
74 Evaluation of the safety and 27 DVTs (31%) overall with IV
efficacy of prophylactic IVC one pulmonary embolism
filter placement in the high- (1.3%) found at follow-up.
risk patient population with One complication (1.3%) in
venographic follow-up the placement of IVC filters
preoperatively.
12 Retrospective evaluation of Two patients (17%) had III
12 patients at high risk of entrapped thrombi on
VTE with prophylactic IVC retrieval of IVC filters. Ten
filter placement for patients (83%) had IVC
pulmonary embolism filters retrieved
incidence/overall successfully.
complications

ACDF = anterior cervical diskectomy and fusion, APCDF = anterior-posterior cervical diskectomy and fusion, DVT = deep vein thrombosis, IPC =
intermittent pneumatic compression, IVC = inferior vena cava, VTE = venous thromboembolism

5,000 IU of UFH three times daily,
either preoperatively or on the day
of surgery, compared with their
previous protocol of SCDs only.
A total of 941 patients in the
SCD-only group were compared
with 992 patients in the UFH
group, with approximately 60% of
patients undergoing thoracolumbar
procedures and 40% undergoing
cervical procedures. The authors
found a significant reduction in
postoperative DVTs in the UFH
group (25 versus 10; P = 0.009),
with similar rates of pulmonary
embolism (six versus five) and epi-
dural hematoma (six versus four).
The authors did not discuss wound
complications related to UFH use.3
The results of this retrospective
study suggest a benefit of early
chemoprophylaxis with UFH in
addition to SCDs in the reduction
of postoperative DVT risk with no
concomitant increase in the risk of
substantial postoperative hemor-
rhage. However, the study may
have been underpowered to dem-
onstrate statistical significance in
evaluating the risk of postopera-
tive epidural hematoma. The rou-
tine use of postoperative UFH for
VTE prophylaxis in patients un-
dergoing spine surgery may re-
duce the incidence of postoperative
DVT, but additional high-quality
studies of large populations are
necessary to assess its safety profile
(Table 3).

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Low-molecular-weight
Heparin
LMWH agents are derived from UFH
and similarly bind to antithrombin III,
inhibiting clotting factor X and indi-
rectly inhibiting thrombin. Evidence
suggests that indirect inhibition of
thrombin may reduce the risk of
bleeding associated with pro-
phylactic anticoagulation.22 An
advantage of LMWH is that its long
half-life allows for daily dosing of the
medication, potentially improving
compliance on an outpatient basis.23
Few retrospective studies have evalu-
ated the efficacy of and risks associ-
ated with the use of LMWH agents as
VTE prophylaxis. A single-institution
retrospective review of 1,954 spine
procedures (ie, 503 cervical, 152 tho-
racic, and 1,299 lumbar) by Gerlach
et al24 evaluated the incidence
of postoperative DVT and epidu-
ral hematoma in patients receiving
nadroparin and SCDs for VTE pro-
phylaxis. Patients received 2,850 IU of
nadroparin daily until discharge. The
SCDs were applied intraoperatively
and postoperatively during hospitali-
zation. Eight patients (0.4%) had
postoperative epidural hematomas
requiring secondary surgery on post-
operative days 1 to 3. One fibular vein
DVT (0.05%) was found in a patient
with unilateral leg swelling. This study
demonstrated a low incidence of peri-
operative VTE and epidural hemor-
rhage with the use of nadroparin but
did not include a control group for
comparison.24
A retrospective review of 367
patients undergoing decompression
and fusion procedures for the man-
agement of degenerative spine disease
(ie, 241 lumbar, 126 cervical; mean 3.7
levels treated) evaluated the efficacy and
risks of postoperative enoxaparin.25
The study used 40 mg daily dosing
of enoxaparin, with SCD use start-
ing at 10:00 PM on postoperative
day 1. No epidural hematomas
occurred in the cohort. Ten patients
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(2.7%) had postoperative DVT, and
four patients (1.1%) had pulmonary
embolism. The authors concluded
that enoxaparin may be safe to start
within 36 hours after spine surgery.25
Compared with other patients, pa-
tients with SCI are at higher risk
of VTE because of immobility and
increased comorbidities.2 A pro-
spective, randomized, blinded mul-
ticenter study compared the efficacy
of UFH/IPC initiated on post-
operative day 1 versus LMWH alone
in the prevention of VTE in 107
patients who underwent surgery for
the management of cord-level (C2 to
T12) SCIs. Patients were randomized
to receive 5,000 IU of UFH every 8
hours with the use of IPC or enox-
aparin 30 mg twice daily. Primary
outcome measures included the inci-
dence of DVT assessed by duplex
ultrasonography and contrast venog-
raphy studies on postoperative day 14.
No difference was found in the inci-
dence of VTE between groups, with
31 of 49 patients receiving UFH
(63.3%) and 38 of 58 patients
receiving LMWH (65.5%) having a
diagnosis of VTE (P = 0.81). The
UFH group had a significantly
higher incidence of pulmonary
embolism than the LMWH group
(ie, nine versus three; P = 0.03), but
no incidence of fatal pulmonary
embolism occurred in either group.
The patients received no baseline
screening for DVT preoperatively,
and the study had a substantial
attrition rate, resulting in small
study populations and possible over-
representation of VTEs26 (Table 3).
Vitamin K Antagonists
Warfarin exerts antithrombotic effects
through inhibition of the enzyme
vitamin K epoxide reductase, which
helps activate clotting factors II, VII,
IX, and X. Data on the use of warfarin
after spine surgery are limited. Rokito
et al27 prospectively evaluated the
efficacy of warfarin in the prevention
Christopher K. Kepler, MD, MBA, et al
of VTE in patients undergoing tho-
racolumbar surgery. In this study, 110
patients undergoing thoracolumbar
surgery were randomized into three
groups: group 1 (42 patients) received
compression stockings, group 2 (33
patients) received compression stock-
ings and SCDs, and group 3 (35
patients) received compression stock-
ings and a 10-mg preoperative dose of
warfarin and postoperative dosing to
a goal international normalized ratio
of 1.8 to 2.0. The incidence of VTE
was compared with that of a non-
randomized control group of 219
patients receiving either SCDs or
compression stockings. All patients
received duplex ultrasonographic
imaging of the bilateral lower
extremities between postoperative
days 5 and 7. None of the ran-
domized patients was symptomatic
for DVT, and no DVT was found
on screening. One DVT was found
in the nonrandomized group. The
overall incidence of DVT was
0.3%. Two patients receiving warfa-
rin (5.7%) had excessive blood loss
(.800 mL). Given the low incidence
of DVT overall, the authors con-
cluded that chemical prophylaxis
such as warfarin may not be neces-
sary and carries a risk of bleeding
perioperatively.27 The North Amer-
ican Spine Society, in their review of
antithrombotic therapies,5 refer-
enced the study by Rokito et al27 and
agreed with their conclusions, sug-
gesting that the study provided level
III therapeutic evidence that the
bleeding risk of warfarin outweighed
its potential benefit in VTE prevention,
with SCDs and compression stockings
providing similar prophylaxis.
Factor X Inhibitors
Factor X inhibitors act by directly
antagonizing factor Xa in the clotting
cascade. These agents have the advan-
tage of daily oral dosing requiring
no routine monitoring. Disadvantages
include the lack of a reversal agent to
7
Venous Thromboembolism Prophylaxis in Spine Surgery
Table 3
Studies Evaluating Pharmacologic Prophylaxis
Study
Cox et al3
Gerlach et al24
Strom and Frempong-
Boadu25
Spinal Cord Injury
Thromboprophylaxis
Investigators26
bid = twice a day, DVT = deep vein thrombosis, IPC = intermittent pneumatic compression, LMWH = low-molecular-weight heparin, SCD = sequential
compression device, SCI = spinal cord injury, UFH = unfractionated heparin, VTE = venous thromboembolism
8 Journal of the American Academy of Orthopaedic Surgeons
Copyright Ó the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Study Design No. of Level of
(Procedure) Patients Intervention Results Evidence
Retrospective 1,933 Review of two In the SCD group, 25 patients III
cohort (cervical/ protocols (SCDs (2.7%) had DVT, 6 patients
thoracolumbar only versus SCD (0.6%) had pulmonary
decompression/ and 5,000 IU of UFH embolism, and 6 patients
fusion) three times daily), (0.6%) had postoperative
evaluating the epidural hematoma. In the
incidence of VTE SCD/UFH group, 10 patients
postoperatively (1.0%) had DVT, 5 patients
(0.5%) had pulmonary
embolism, and 4 patients
(0.4%) had epidural
hematoma. This reduction in
DVT after implementation of
the protocol was statistically
significant (P = 0.009).
Retrospective 1,954 Evaluation of the use The hemorrhage rate among IV
case series of nadroparin and patients receiving nadroparin
(cervical/ incidence of was 0.4% (8 of 1,954 patients).
thoracolumbar postoperative Ten (77%) of the 13 patients
decompression/ hematoma with major postoperative
fusion) hematoma demonstrated
progressive neurologic deficit,
which resolved in 6 patients
and resulted in hematoma-
related morbidity in 4 patients
(31%). Only one patient
(0.05%) in this series had
clinically evident DVT. No
patients had pulmonary
embolism.
Retrospective 367 Evaluation of the No patients receiving LMWH 24 IV
single-surgeon safety and efficacy to 36 hr after surgery had
case series of LMWH as VTE postoperative hemorrhage
(cervical/lumbar prophylaxis 24 to 36 (95% confidence interval,
laminectomy hr after zero to 0.8%). Nearly half of
and/or fusion) decompression/ the study population
fusion for the underwent lower extremity
management of ultrasonography or chest CT.
degenerative spine Acute VTE was diagnosed in
disease 14 patients (3.8%; 95%
confidence interval, 2.1%–
6.3%).
Prospective 107 Comparison of UFH/ Among 107 assessable I
randomized IPC versus LMWH patients, the incidence of VTE
multicenter 30 mg bid, was 63.3% with UFH/IPC
cohort study evaluating DVT, versus 65.5% with enoxaparin
(surgical pulmonary (P = 0.81). The incidence of
management of embolism, and pulmonary embolism was
SCIs from C2 to major bleeding after 18.4% with UFH/IPC versus
T12) 2 wk of prophylaxis 5.2% with enoxaparin (P =
0.03). Among all randomized
patients, the incidence of
major bleeding was 5.3% with
UFH/IPC versus 2.6% with
enoxaparin (P = 0.14).
(continued )
 Christopher K. Kepler, MD, MBA, et al

Table 3 (continued )
Studies Evaluating Pharmacologic Prophylaxis
Study Design No. of Level of
Study (Procedure) Patients Intervention Results Evidence

Du et al28 Prospective 665 Oral rivaroxaban 10 No difference was found in VTE I

randomized mg daily versus outcomes (P . 0.05) or in
controlled trial subcutaneous postoperative bleeding (P .
(lumbar surgery) parnaparin 40 mg 0.25).
daily for VTE
prophylaxis,
evaluating efficacy
in prevention of
bleeding
Cuellar et al34 Retrospective 200 Evaluation of patients The acetylsalicylic acid II
cohort study with cardiac stents continuation group had a
(cervical or undergoing spinal shorter hospital length of stay
lumbar surgery, with 100 on average (4.1 6 2.7 versus
decompression/ patients continuing 6.2 6 5.8 d; P , 0.005), as
fusion) acetylsalicylic acid well as a reduced surgical
perioperatively and time (210 6 136 versus 266
100 discontinuing 6 143 min; P , 0.01). No
acetylsalicylic acid notable difference was found
perioperatively, to in estimated blood loss (642
assess 6 905 versus 697 6 1,187),
perioperative the amount of blood products
morbidity transfused, overall rate of
intraoperative and
postoperative complications
(8% versus 11%), or 30-
d hospital readmission rate
(5% versus 5%). No clinically
notable spinal epidural
hematoma was observed in
either of the study groups.
Rokito et al27 Prospective 329 110 randomized None of the randomized group II
randomized patients in three had symptoms of DVT, and no
controlled study groups (ie, DVT was found on screening.
compression One of the nonrandomized
stockings; SCDs patients had DVT (overall
and compression incidence 0.3%). Two patients
stockings; in the warfarin group had
compression major blood loss (.800 mL).
stockings and
warfarin) versus 219
nonrandomized
patients (ie,
compression
stockings or SCDs),
examining DVT
incidence and
perioperative
complications, with
all patients receiving
postoperative
Doppler
ultrasonography

bid = twice a day, DVT = deep vein thrombosis, IPC = intermittent pneumatic compression, LMWH = low-molecular-weight heparin, SCD = sequential
compression device, SCI = spinal cord injury, UFH = unfractionated heparin, VTE = venous thromboembolism

Month 2018, Vol 0, No 0 9

Copyright Ó the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Venous Thromboembolism Prophylaxis in Spine Surgery
manage severe hemorrhage. Factor Xa
inhibitors include rivaroxaban and
apixaban, both of which have demon-
strated efficacy in the prevention of
VTE events without increased post-
operative bleeding in lower extremity
surgery. Data regarding their use after
spine surgery are limited. One pro-
spective randomized trial, by Du
et al,28 compared the efficacy of
postoperative rivaroxaban versus
parnaparin (LMWH) in the pre-
vention of VTE and postoperative
bleeding in patients undergoing lum-
bar surgery. In this study, 665 patients
were randomized to either daily oral
rivaroxaban (10 mg) or daily sub-
cutaneous injection of parnaparin (40
mg) beginning 6 to 8 hours post-
operatively for 14 days. No difference
was found in the incidence of symp-
tomatic VTE between the patients
receiving rivaroxaban (0.9%) and
those receiving parnaparin (1.9%);
P . 0.25. In addition, no difference
was found in postoperative bleeding
events between the rivaroxaban group
(6.2%) and the parnaparin group
(6.2% and 5.2%, respectively; P .
0.5). Two patients (0.5%) receiving
rivaroxaban required secondary sur-
gery for the management of clinically
notable postoperative hematoma, and
seven patients (2%) had clinically
notable wound drainage resulting in
delayed wound healing or infection
(Table 3). Rivaroxaban offered efficacy
equivalent to LMWH in the prevention
of VTE with similar incidence of
postoperative hematoma formation in
patients undergoing lumbar surgery.28
Antiplatelet Agents
Acetylsalicylic acid (ie, aspirin) and
thienopyridines (eg, clopidogrel) exert
an irreversible effect on platelet aggre-
gation that can last up to 7 to 10
days.29 A growing body of evidence
supports the use of acetylsalicylic acid
over other chemoprophylactic agents
in the reduction of clinically significant
VTE, wound drainage, and infection
10
Copyright Ó the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
in patients undergoing lower extrem-
ity arthroplasty.30,31 Antiplatelet
agents are not considered for VTE
chemoprophylaxis in patients under-
going spine surgery because of their
effect on early hemostasis and the
risk of postoperative bleeding and
epidural hematoma.29,32 In fact,
antiplatelet agents are often dis-
continued as early as 1 week before
spine surgery because of the risk of
postoperative epidural hematoma.33
A recent retrospective cohort study by
Cuellar et al34 compared perioperative
outcomes of 100 patients with cardiac
stents undergoing lumbar spine sur-
gery in whom acetylsalicylic acid was
stopped 5 days before surgery com-
pared with 100 patients who con-
tinued their acetylsalicylic acid
regimen perioperatively. The authors
found no difference in the estimated
blood loss, postoperative complica-
tion rate, or 30-day readmission rate
between the groups, while the patients
continuing their regimen had reduced
surgical times and a shorter average
hospital length of stay.34 Although
this study may suggest that the peri-
operative use of antiplatelet agents is
safe in patients undergoing spine sur-
gery, it is limited by its retrospective
nature and the number of patients.
Because postoperative epidural
hematomas occur infrequently, fur-
ther studies with larger study pop-
ulations are necessary to determine the
safety of antiplatelet agents in patients
undergoing spine surgery (Table 3).
Timing of Prophylaxis
No consensus has been reached
regarding the timing of chemoprophy-
laxis in patients undergoing spine sur-
gery. Ploumis et al35 surveyed 47 spine
surgeons regarding their timing of VTE
prophylaxis in elective and SCI
patients. For SCI patients, 27 respon-
dents (57.4%) reported initiating VTE
prophylaxis between postoperative
days 0 and 2, with 18 respondents
Journal of the American Academy of Orthopaedic Surgeons
(38.3%) beginning it on postoperative
days 3 to 7. For non-SCI patients,
equal numbers of surgeons (21
[44.7%] each) responded that they
initiated VTE prophylaxis on post-
operative days 0 to 2 and on post-
operative days 3 to 7.35 The results
suggest that surgeons may be more
aggressive in the timing of VTE pro-
phylaxis in SCI patients than in other
patients.
A retrospective level III review of
206 patients undergoing surgery for
the management of traumatic cervi-
cal or thoracolumbar spine fractures
compared the outcomes of patients
receiving early (zero to 48 hours after
surgery) versus late (.48 hours after
surgery) initiation of LMWH for
anticoagulation.36 Patients received
subcutaneous heparin 5,000 IU twice
daily (6 patients), dalteparin 5,000
IU daily (36 patients), enoxaparin 40
mg daily (89 patients), or enoxaparin
30 mg twice daily (75 patients). Forty-
eight patients (23.3%) received early
VTE prophylaxis, and 158 patients
(76.7%) received late VTE pro-
phylaxis. No patients had epidural
hematoma or postoperative bleeding
necessitating intervention in either
group. Thirteen patients (6.2%) had
VTEs (11 DVTs; 2 pulmonary emb-
olisms), 12 of which occurred in the
late prophylaxis group. In addition,
patient age $45 years (OR, 5.12; P =
0.048) and concomitant traumatic
brain injury (OR, 6.94; P = 0.031)
were independently associated with an
increased risk of VTE. The authors of
the study concluded that pharmaco-
logic VTE prophylaxis initiated within
48 hours of surgical fixation of trau-
matic spine fractures does not increase
the risk for bleeding, progression of
neurologic injury, or postoperative
complications, while reducing the rate
of VTE.36
A systematic review of five studies
(three of which were randomized
controlled trials) by Christie et al37
evaluated the timing of VTE pro-
phylaxis in 1,948 patients with acute

SCI. The authors of the review gave
strong recommendations to start
VTE prophylaxis, specifically LMWH,
within 72 hours of SCI and within 24
hours after surgery for fixation of
acute SCI. Timing of VTE prophylaxis
should be determined on a case-by-
case basis, with the limited evidence
suggesting that in patients with SCI,
the risk of VTE is higher and may
warrant earlier and more frequent
VTE prophylaxis, whereas patients
undergoing elective procedures may
require only postoperative mechanical
VTE prophylaxis, given the low inci-
dence of VTE. Randomized controlled
trials evaluating the timing of VTE
prophylaxis in a homogeneous pop-
ulation are needed.
Authors’ Experience
At our institution, all patients under-
going spine surgery are treated with
pneumatic compression devices peri-
operatively and throughout their
hospital stay unless medically contra-
indicated. Early postoperative mobili-
zation is emphasized. All patients are
mobilized within 12 hours of surgery
by either physical therapy or nursing
staff unless mobilization is otherwise
contraindicated. Patients undergoing
posterior lumbar surgery below the
cord level receive 5,000 IU of heparin
subcutaneously every 8 hours starting
on postoperative day 1 at 6:00 AM.
Patients undergoing cervical spine or
posterior thoracolumbar surgery at
the cord level receive subcutaneous
heparin starting on postoperative day
2. Patients undergoing anterior tho-
racolumbar surgery receive 30 mg of
enoxaparin daily starting on post-
operative day 1 because of concern
for increased VTE risk with great
vessel manipulation. Postoperatively,
patients are not routinely screened for
VTE unless they demonstrate con-
cerning clinical findings or evaluation
is recommended by the medical con-
sultant overseeing the patient’s con-
Month 2018, Vol 0, No 0
Copyright Ó the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
dition. Management of postoperative
VTE is coordinated with the recom-
mendations of vascular medicine spe-
cialists, with the patient’s clinical
circumstance taken into account.
Patients with a history of VTE who
are scheduled for elective spine surgery
will receive a preoperative vascular
medicine consultation, and the use of
an IVC filter may be considered if
indicated.
Summary
Venous thromboembolism is an infre-
quent complication with the potential
for substantial morbidity after spine
surgery. Patients with reduced mobil-
ity, especially after SCI, are at increased
risk of VTE. The risk of VTE compli-
cations is higher in patients who
undergo longer surgical procedures,
patients with more comorbidities,
especially history of malignancy or
clotting disorder, and patients with
preoperative immobility. Early ambu-
lation and ICP use have been shown to
be beneficial in the prevention of VTE.
In higher-risk patient populations, IVC
filters can be considered. Pharmaco-
logic prophylaxis should be reserved
for patients who will likely have
longer surgical times, multilevel
thoracolumbar surgery, and anterior
thoracolumbar surgical approaches.
The risk of epidural hematoma after
pharmacologic prophylaxis is low, but
this complication carries a high risk of
substantial morbidity. More robust,
prospective studies with higher levels
of evidence are needed to determine the
optimal type and timing of VTE pro-
phylaxis for both degenerative and
traumatic spine surgery patients.
References
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table of contents. In this article, ref-
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Christopher K. Kepler, MD, MBA, et al
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