Prevention of Venous Thromboembolic Disease in Adult Nonorthopedic Surgical Patients - UpToDate

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Prevention of venous thromboembolic disease in adult

nonorthopedic surgical patients
Authors: James D Douketis, MD, FRCPC, FACP, FCCP, Siraj Mithoowani, MD, MHPE, FRCPC
Section Editors: Jess Mandel, MD, MACP, ATSF, FRCP, David A Garcia, MD
Deputy Editors: Geraldine Finlay, MD, Kathryn A Collins, MD, PhD, FACS
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2023. | This topic last updated: Feb 17, 2023.
INTRODUCTION
Venous thromboembolism (VTE; deep venous thrombosis and pulmonary embolism [PE]) is
common in the postoperative setting with over half of this population at moderate risk for
VTE [1-3]. PE is one of the most common preventable causes of in-hospital deaths following
surgery [4-8].
Nonorthopedic surgeries include surgery of the skin and soft tissues of the trunk or
extremities; surgery involving the chest, abdomen, or pelvic organs; and surgery of the head
(including brain) and neck. Our approach to the prevention of VTE in nonorthopedic surgical
patients will be reviewed here. Our approach is, for the most part, in keeping with
recommendations from several societies, including the American College of Chest Physicians
(ACCP) and the American Society of Hematology (ASH) [9-11]. Prevention of VTE in patients
undergoing orthopedic procedures (eg, joint repair/replacement) and in hospitalized
medical patients are presented separately. (See "Prevention of venous thromboembolism in
adults undergoing hip fracture repair or hip or knee replacement" and "Prevention of
venous thromboembolic disease in acutely ill hospitalized medical adults".)
ASSESS RISK FOR THROMBOSIS
The risk of postoperative VTE should be assessed prior to surgery and the patient stratified
into very low, low, moderate, or high-risk groups so that an appropriate method of VTE
prevention can be selected [12]. (See 'Baseline thrombosis risk' below and 'Thrombosis risk
model (Caprini)' below.)
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VTE risk largely depends upon the procedure but patient-related factors also play a role:
● Procedure-related – Many procedure-related factors contribute to the risk of VTE in

nonorthopedic patients including the extent and duration of surgery, intraoperative
positioning, the type of anesthesia, and postoperative mobility. In general, the highest
risk is in those undergoing major surgery (defined as surgery lasting longer than 45
minutes [13]), abdominal and thoracic cavity surgery (eg, major abdominal/pelvic or
surgery for malignancy), prolonged surgery (≥2 hours), emergency rather than elective
surgery, postoperative immobilization for ≥4 days, as well as critically ill patients who
are confined to bed (eg, extensive burns, multiple trauma, brain/spine injury) [13-16].
The risk is generally low for patients undergoing minor, typically ambulatory
procedures (eg, elective hernia repair, thyroid surgery, minor skin excision, carotid
endarterectomy).
● Patient-related – Patient-related VTE risk factors are discussed separately. (See

"Overview of the causes of venous thrombosis".)
Baseline thrombosis risk — The baseline risk of VTE associated with individual surgeries is
highly variable reflecting the wide range of surgeries within each specialty [12,17].
Importantly, estimates of baseline risk are imperfect since they use data from studies in
populations not on VTE prophylaxis and populations on prophylaxis, or use extrapolated
data from related populations.
General, abdominal/pelvic, bariatric, vascular, plastic surgery — The risk categories

(very low, low, moderate, high) correspond to the Caprini model ( table 1) discussed below,
although in practice many experts use clinical gestalt to estimate the risk. (See 'Thrombosis
risk model (Caprini)' below.)
● General/abdominal pelvic (low to high Caprini score) – Rates of symptomatic VTE

derived from untreated groups in randomized trials [18-30] have ranged from 0.5 to 1.6
percent, higher among those undergoing surgery for malignancy (up to 3.7 percent)
[6,18]. However, several studies report that VTE risk is wide in this population since it
encompasses a broad range of surgeries from laparoscopic appendectomy to open
pelvic surgery for cancer.
● Bariatric surgery (low to high Caprini score) – Observational data suggest that while
in the past rates were between 1.9 and 5.4 percent [31,32], advances in less extensive
bariatric surgery may be associated with lower rates (0.5 percent) according to data
from the American College of Surgeons National Surgical Quality Improvement
Program (ACS-NSQIP) [33].
● Noncardiac vascular surgery (low to high Caprini score) – Baseline risk in the
absence of prophylaxis is extrapolated from the population of patients undergoing
abdominal/pelvic operations since vascular procedures were commonly included in
those studies. Small observational studies comparing pharmacologic prophylaxis with
no prophylaxis in only vascular surgery patients report variable rates for open
abdominal vascular surgery (up to 10 percent) [34-41], peripheral artery surgery (1.8 to
9 percent) [42-46], venous ablation procedures (<1 percent) [47-57], and lower
extremity amputation (2 to 15 percent, higher for above knee compared with below-
knee) [37,58-62].
● Plastic and reconstructive (low to high Caprini score) – In the absence of

pharmacologic prophylaxis, the baseline risk as estimated by the American College of
Chest Physicians (ACCP) is between 0.5 to 1.8 percent based upon three observational
studies [12,63-65]. However, extrapolating from related surgical populations (breast
surgery, lower extremity bypass surgery), the estimated baseline VTE risk ranges from
low (eg, outpatient cosmetic procedures) to high (eg, reconstructive surgeries).
Cardiac, thoracic, neurosurgery, major trauma — The ACCP has provided rough

estimates of the baseline risk for VTE, in the absence of prophylaxis, for the other
nonorthopedic surgical specialties [12]. The risk categories in parenthesis below correspond
to the Caprini model, although this scoring system ( table 1) has not been validated in
these populations, and most experts use gestalt assessment. (See 'Thrombosis risk model
(Caprini)' below.)
● Cardiac surgery (moderate to high Caprini score) – Several studies have identified
rates of VTE up to 1 percent in this population (prophylaxis unknown) [6,66,67] but
older studies suggest higher rates (up to 25 percent) in the absence of prophylaxis [68-
70].
● Noncardiac thoracic surgery (moderate to high Caprini score) – Several studies

reported that the incidence of symptomatic VTE ranges from 0.18 to 7.4 percent
(highest in pneumonectomy, esophagectomy, extended resection) [6,66,71-73].
● Neurosurgery (moderate to high Caprini score) – Meta-analyses report a pooled

incidence of VTE in untreated patients between 16 and 29 percent, highest in those
undergoing craniotomy [29,30]. In studies limited to spinal surgery, the incidence of
deep vein thrombosis (DVT) ranges from 0 to 15 percent (with and without prophylaxis)
[74-80]. Limited spine surgeries for benign conditions and cervical spine surgery are
associated with less risk [74,75].
● Major trauma (moderate to high Caprini score) – While studies report an incidence
of DVT as high as 58 percent among those not receiving prophylaxis [81], these rates
may reflect the most seriously ill patients with multiple other injuries (eg, traumatic
brain and spinal injury) [82-87]. However, a 2013 systematic review, reported lower
incidences of DVT and PE in patients who received either no prophylaxis (8.7 percent)
or only mechanical prophylaxis (3.7 percent) [88]. Accurate estimates have been
hampered by a baseline risk that varies widely in this population since these patients
often undergo abdominal, vascular, neurologic, and/or orthopedic surgeries [81-87,89-
91].
Thrombosis risk model (Caprini) — Although there have been many attempts to quantitate
VTE risks, no one method has been found to be universally acceptable and many physicians
use a gestalt assessment [12-14,92-94]. Nonetheless, the most widely used model is the
Modified Caprini Risk Assessment Model (ie, Caprini score modified by the ACCP ( table 1)
[12]). The Rogers score is less frequently used and has not been externally validated [14].
Using the Caprini score, patients undergoing surgical procedures are classified according to
their estimated baseline risk (EBR) for VTE in the absence of thromboprophylaxis as (see
'Baseline thrombosis risk' above):
● Very low risk – Caprini score 0; corresponding to an EBR <0.5 percent (see 'Very low
thrombosis risk: Early ambulation' below)
● Low risk – Caprini score 1 to 2; corresponding to an EBR of about 1.5 percent (see 'Low
VTE risk: Mechanical methods' below)
● Moderate risk – Caprini score 3 to 4; corresponding to an EBR of about 3 percent (see

'Moderate or high VTE risk' below)
● High risk – Caprini score ≥5; corresponding to an EBR of at least 6 percent (see
'Moderate or high VTE risk' below)
The caveat of this model is that it has been validated, and is therefore, only applicable to
patients undergoing general (eg, breast, thyroid, parathyroid) and abdominal/pelvic surgery
(eg, gastrointestinal, urologic, gynecologic), including those who are critically ill [12,92,94-
96]. Although not validated in other populations, it is considered by most experts as
acceptable for use in those undergoing bariatric and vascular surgery. In addition, this
model underwent further modification for patients undergoing plastic/reconstructive
surgery since a validation study reported a lower risk of VTE for a given Caprini score in this
population (0.6 percent among those with a score of 3 to 4, 1.3 percent with a score of 5 to 6,
2.7 percent with a score 7 to 8, and 11.3 percent with a score of >8).
ASSESS RISK FOR MAJOR BLEEDING
For patients in whom pharmacologic VTE prophylaxis is indicated, a full history and
examination should be obtained to assess the risk for major bleeding. Major bleeding is
defined as fatal bleeding, and/or symptomatic bleeding in a critical area or organ (perhaps
requiring reexploration), and/or bleeding causing a fall in hemoglobin of ≥2 g/dL or leading
to transfusion of two or more units of whole blood or red cells [97]. When assessing the risk,
we prefer that the baseline risk be assessed first and then modified according to the
potential consequences of bleeding and individual risk factors discussed below. (See
'Estimates of baseline bleeding risk' below and 'Individual risk factors for bleeding' below
and 'Bleeding risk categories' below.)
The rate of bleeding associated with pharmacologic prophylaxis varies among patient
groups. One meta-analysis of 51 randomized trials of pharmacologic VTE prophylaxis in
general surgery patients reported that minor bleeding was common and included injection
site bruising (7 percent), wound hematoma (6 percent), drain site bleeding (2 percent), and
hematuria (2 percent) [98]. Major bleeding complications were uncommon and included
including gastrointestinal tract (0.2 percent) or retroperitoneal (<0.1 percent) bleeding.
Discontinuation of prophylaxis occurred in 2 percent of patients and subsequent reoperation
for bleeding occurred in less than 1 percent.
Estimates of baseline bleeding risk — Baseline bleeding risk has been poorly studied in
nonorthopedic surgical patients. Although several studies have attempted to elucidate
bleeding risk [12,99], risk stratification for major bleeding has been estimated by the
American College of Chest Physicians (ACCP) in the following patient groups as [12]:
● General/abdominal/pelvic surgery – 1 percent
● Bariatric surgery – <1 percent
● Plastic and reconstructive surgery – 0.5 to 1.8 percent
● Vascular surgery – 0.3 to 1.8 percent
● Cardiac surgery – 5 percent (high risk)
● Thoracic surgery – 1 percent
● Neurosurgery – Craniotomy: 1 to 1.5 percent; spinal surgery: <0.5 percent
● Major trauma – 3.4 to 4.7 percent (high risk)
Individual risk factors for bleeding — Patients with individual risk factors for bleeding
include those with active bleeding as an indication for surgery (eg, gastrointestinal bleeding,
trauma, ruptured aneurysm), patients with intracranial hemorrhage, patients who develop a
moderate or severe coagulopathy (eg, patients with liver disease), and patients with an
underlying bleeding disorder or thrombocytopenia (eg, platelet count <50,000/microL, or

<100,000/microL plus additional risk factors for bleeding). Patients with relative
contraindications include those with recurrent bleeding from multiple gastrointestinal
telangiectasias. Epistaxis and menstrual bleeding are not contraindications to
pharmacologic thromboprophylaxis. (See "Prevention of venous thromboembolic disease in
acutely ill hospitalized medical adults", section on 'Bleeding risk assessment'.)
Bleeding risk categories — Following the above assessment, bleeding risk can be

categorized as either low or high.
● Low bleeding risk – In general, patients undergoing general, abdominal-pelvic,

bariatric, vascular, and thoracic surgery that is uncomplicated tend to have lower rates
of bleeding (<2 percent) when compared with other patients.
● High bleeding risk – Patients undergoing cardiac surgery and patients with major
trauma, especially involving the brain and spine [80], are at highest risk of bleeding (>3
percent). Patients in this category also include those in whom the consequences of
bleeding are considered potentially devastating; for example, patients undergoing
neurosurgical procedures where thromboprophylaxis may result in spinal or
intracranial hemorrhage and patients undergoing plastic/reconstructive surgery where
thromboprophylaxis may result in injury or rejection of grafted tissue due to bleeding.
Similarly, patients with one or more individual risk factors for bleeding are considered
at high risk of bleeding postoperatively. Prophylaxis in this population is discussed
below. (See 'With high bleeding risk: Mechanical methods' below.)
SELECTING THROMBOPROPHYLAXIS
Options for primary VTE prophylaxis include early ambulation, pharmacologic and/or
mechanical methods. VTE prevention strategies should be individualized according to the
risk of VTE (very low, low, moderate, and high) as well as the risk and consequences of major
bleeding. (See 'Assess risk for thrombosis' above and 'Assess risk for major bleeding' above.)
The approach outlined in the sections below is, in general, consistent with international
guidelines including the American Society of Hematology (ASH), American College of Chest
Physicians (ACCP), the Asian Venous Thrombosis Forum, Korean guidelines for the
Prevention of Venous Thromboembolism, European guidelines on perioperative venous
thromboembolism prophylaxis: Executive summary, and the International Consensus
Statement on the Prevention and Treatment of Venous Thromboembolism [12,100-106].
Importantly, the approach assumes that patients are at low risk for bleeding. In addition,
the decision is fluid such that individual circumstances before, during, and after surgery may
alter the decision regarding method selection. In addition, individualizing the approach
according to individual factors is also prudent. Clinicians should also be aware that in
general, thromboprophylaxis reduces but does not eliminate VTE events and VTE-related
mortality [26,66,107,108].
Noteworthy, methods of secondary prophylaxis (eg, surveillance imaging) and inferior vena
cava filters are not recommended for VTE prevention in this population.
Various strategies to improve the use of thromboprophylaxis methods have been

demonstrated to be effective, including computerized order sets with electronic alerts, or
preprinted orders and quality improvement in the form of clinician education programs,
audit, and feedback [3,109-115]. Further efforts are required to improve the use of
thromboprophylaxis in clinical practice.
Very low thrombosis risk: Early ambulation — The risk of VTE is considered very low when
the baseline risk in the absence of prophylaxis is estimated to be less than 0.5 percent
( table 1). Very low-risk group surgeries generally include patients undergoing general or
abdominal/pelvic surgery with a Caprini score of zero or patients undergoing
plastic/reconstructive surgeries with a Caprini score of zero to two. Examples include healthy
young patients undergoing minor outpatient procedure (eg, LASIK surgery, cataract
removal, skin biopsy, benign breast biopsy, diagnostic endoscopy, nasal polyp removal,
dilatation and curettage, colposcopy, fluid removal from joint effusion).
For nonorthopedic surgical patients at very low risk of VTE, we recommend early and
frequent ambulation rather than pharmacologic or mechanical methods of prophylaxis.
Most very low-risk patients are able to ambulate easily after surgery. Mechanical methods
may be employed in the unusual circumstance where unexpected issues occur during the
procedure (eg, bleeding, more extensive surgery, which intrinsically change the risk
category) or the patient has a complication and requires admission.
Since there are no randomized trials comparing ambulation with other methods, this
approach is largely based upon the rationale that the baseline rate of VTE in this population
is too low (<0.5 percent) to warrant prophylaxis. In addition, indirect data from studies
evaluating the risk of VTE in orthopedic patients have also suggested that the risk of VTE is
lowered by 70 percent in those who ambulate on or before the second postoperative day
[116]. (See "Prevention of venous thromboembolism in adults undergoing hip fracture repair
or hip or knee replacement", section on 'Risk of thrombosis'.)
Low VTE risk: Mechanical methods — The risk of VTE is considered low when the baseline
risk in the absence of prophylaxis is estimated to be 1.5 percent ( table 1). Patients in this
category include those undergoing general or abdominal/pelvic surgery with a Caprini score
of 1 to 2 or patients undergoing plastic/reconstructive surgery with a Caprini score of 3 to 4.
Examples include those undergoing minor elective abdominal-pelvic surgery (eg,
appendectomy, laparoscopic cholecystectomy) or minor thoracic surgery (eg, diagnostic

thoracoscopy, video-assisted biopsy). Other examples include patients undergoing minor
vascular procedures (eg, vein ablation), and elective spine surgery (eg, spinal fusion [117]).
(See 'Baseline thrombosis risk' above.)
For nonorthopedic surgical patients at low risk for VTE, we suggest mechanical methods of
VTE prophylaxis rather than pharmacologic prophylaxis or no prophylaxis. The rationale for
this approach is that the risk of VTE is high enough to justify thromboprophylaxis but does
not warrant the risk of bleeding associated with pharmacologic methods. Switching to
pharmacologic methods may be appropriate in this with individual risk factors for VTE (eg,
history of recurrent VTE or cancer).
Mechanical methods of thromboprophylaxis include intermittent pneumatic compression

(IPC), graduated compression stockings (GCS, also known as elastic stockings), and the
venous foot pump (VFP). Although IPC devices may be superior and are preferred by the
ACCP, experts generally choose IPC or GCS since the data comparing one device over the
other is fundamentally flawed [12,118-120].
Intermittent pneumatic compression and venous foot pump — Data supporting the use
of IPC for the prevention of VTE in nonorthopedic surgical patients are limited. However, of
the mechanical devices (IPC, GCS, VFP), efficacy appears best with IPC use ( picture 1)
[118,120-122]. Meta-analyses of small randomized trials of mixed surgical populations
(including general, abdominal, urologic, neurosurgery, oncologic, orthopedic) report that IPC
use is superior to no prophylaxis and to GCS, and may offer additive benefit to surgical
patients on low molecular weight (LMW) heparin [12,121,123-127]. (See 'With low bleeding
risk: Combined prophylaxis' below.)
As an example, the largest meta-analysis, which included data on 16,164 patients (mostly
surgical) enrolled in 70 trials, reported that IPC was more effective than no prophylaxis in
reducing deep venous thrombosis (DVT; 7.3 versus 16.7 percent) and pulmonary embolism
(PE; 1.2 versus 2.8 percent) without any effect on mortality [123]. Although the addition of
pharmacologic prophylaxis to IPC further reduced the risk of DVT (relative risk [RR] 0.54, 95%
CI 0.32-0.91), it had no effect on the incidence of PE. In another meta-analysis of eight
studies that compared mechanical prophylaxis with LMW heparin, the risk of DVT
(symptomatic and asymptomatic) was 80 percent higher in those who had mechanical
methods of prophylaxis (RR 1.80, 95% CI 1.16-2.79) [122] with a 57 percent decrease in the
risk of major bleeding. However, patients in these studies had a range of VTE risk and many
were of moderate to high risk.
Randomized studies showing efficacy of VFP devices ( picture 2) in surgical patients are
lacking but, similar to IPC devices, they prevent thrombosis by stimulating lower limb venous
flow [128,129].
Compliance, proper fit, and discomfort are major issues with IPC devices. Devices may be
removed while the patient is ambulating but should be put back on when the patient returns
to a seated or supine position. However, reflective of practice, observational studies report
frequent errors in IPC application [130-132]. This suggests that frequent interference with
the device is common and may potentially interfere with efficacy. Battery-operated devices
may improve compliance in the future.
IPC is contraindicated in patients with evidence of leg ischemia (eg, peripheral artery
disease). Although there are no data available on skin complications of IPC use, skin
breakdown is a known complication, especially in frail, older adults, although some clinicians
use loose stockinettes underneath the device to counteract this phenomenon. In addition,
practical considerations for amputees or patients with burns or extensive skin lesions (eg,
Stevens Johnson's syndrome) may limit IPC application. In this context, although one device
can be applied to any extremity, its efficacy in the prevention of VTE is not assured and likely
limited. There is also a hypothetical concern that patients who have been immobilized for a
period of ≥72 hours without any form of prophylaxis may be at risk of dislodging recently
formed venous clot in the lower extremities. The value of clinical examination or ultrasound
in determining risk of clot dislodgement following the application of IPC in this setting is
unknown.
Optimal timing of IPC in surgical patients is poorly studied. However, one study suggested
that IPC should be started as soon as possible, preferably just before surgery or in the
operating room and continued with few interruptions until discharge [133]. (See 'Timing of
initiation' below.)
IPC devices are thought to prevent VTE by enhancing blood flow in the deep veins of the
legs, thereby preventing venous stasis [134]. IPC also reduces plasminogen activator
inhibitor-1 (PAI-1), thereby increasing endogenous fibrinolytic activity [135]. (See
"Thrombotic and hemorrhagic disorders due to abnormal fibrinolysis", section on 'PAI-1'.)
Graduated compression stockings — There is a paucity of high quality randomized trials

that have studied the efficacy of GCS for preventing VTE in the surgical population [120,136-
140]. GCS alone are effective at preventing DVT but may be less effective than
pharmacologic agents. However, GCS when combined with other prophylactic methods
appears to improve rates of DVT prevention. Of note, GCS refer to prescription-style
stockings and not antiembolism stockings, which are widely available in most facilities. (See
'With low bleeding risk: Combined prophylaxis' below.)
As examples:
● One meta-analysis of 20 randomized trials mostly surgical and orthopedic

patients(mixed populations) reported that the use of GCS alone was more effective
than no prophylaxis in the prevention of DVT (21 versus 9 percent; odds ratio [OR] 0.35,
95% CI 0.28-0.43) [141].
● In another meta-analysis of eight studies (mostly hospitalized general surgical and

orthopedic patients), the incidence of proximal DVT and PE was lower in patients
treated with GCS compared with patients without GCS (1 versus 5 percent, 2 versus 5
percent, respectively) [140]. However, addition of a second method of prophylaxis in
some of the included trials may have biased the favorable outcome associated with
GCS in this analysis.
● Trials reporting the efficacy of GCS when combined with pharmacologic prophylaxis are
discussed below. (See 'With low bleeding risk: Combined prophylaxis' below.)
The efficacy and safety of thigh- versus knee-length stockings has not been studied in
surgical patients.
Optimal timing of GCS in surgical patients is unstudied. However, in general, GCS should be
started as soon as possible, preferably before surgery, or in the operating room and
continued with few interruptions until discharge. (See 'Timing of initiation' below.)
Contraindications against their use and local skin breakdown complications are similar to
those for IPC. (See 'Intermittent pneumatic compression and venous foot pump' above.)
Moderate or high VTE risk — The risk of VTE is considered moderate when the baseline risk
in the absence of prophylaxis is estimated to 3 percent and high if it is at least 6 percent
( table 1). (See 'Baseline thrombosis risk' above.)
● Moderate-risk surgical patients have been defined as patients undergoing general or

abdomen/pelvic surgery with a Caprini score of 3 to 4 or patients undergoing
plastic/reconstructive surgery with a Caprini score of 5 to 6 ( table 1). Patients
undergoing major gynecologic and urologic surgery usually fall into the moderate risk
category [142]. In addition, patients undergoing major cardiac or thoracic surgery,
bariatric surgery, and neurosurgical procedures, and patients with nonextensive
trauma not involving the brain or spine are, at minimum, also considered moderate
risk for VTE.
● High-risk surgical patients have been defined as patients undergoing general or

abdominal/pelvic surgery with a Caprini score of 5 or more ( table 1) or patients
undergoing plastic/reconstructive surgery with a Caprini score of 7 to 8. Examples of
patients in the high-risk group are those undergoing extensive thoracic or abdominal-
pelvic surgery (eg, distal colorectal surgery, extensive pelvic surgery, lung cancer
resection, esophagectomy, brain cancer resection), major trauma (particularly if
involving the brain or spinal cord), acute spinal cord injury, or cancer surgery [143,144].
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With low bleeding risk: Pharmacologic alone — In nonorthopedic surgical patients at

moderate risk for VTE and in whom the risk of bleeding is low, we suggest pharmacologic
prophylaxis, rather than mechanical methods, while in those at high VTE risk we
recommend pharmacologic prophylaxis rather than mechanical methods. The rationale for
this approach is based upon randomized trials and meta-analyses with data for patients at
moderate risk being weaker than for those at high risk. For select patients in whom the risk
of VTE is considered to be particularly high, we suggest the addition of mechanical to
pharmacologic methods (eg, multiple risk factors, surgery for cancer). (See 'With low
bleeding risk: Combined prophylaxis' below and 'Pharmacologic dosing' below.)
Among the available agents, low molecular weight (LMW) heparin is generally the preferred
anticoagulant based upon randomized trials that report superior or similar efficacy with
unfractionated heparin (UFH) or fondaparinux, although most data show no appreciable
effect on mortality and limited effect on clinically relevant bleeding. For those with renal
insufficiency (creatinine clearance <20 to 30 mL/min) or for those in whom cost is an issue,
UFH is appropriate ( table 2). For patients in whom UFH or LMW heparin is contraindicated
(eg, heparin-induced thrombocytopenia [HIT]) or unavailable, fondaparinux or mechanical
methods are preferred. Timing of initiation and dosing of these agents are discussed below.
(See 'Administration' below.)
Many experts administer more aggressive prophylaxis in very high-risk populations in the
form of increased intensity of a pharmacologic agent (eg, three times a day UFH, twice daily
enoxaparin) and/or the addition of a mechanical device (usually IPC). Patients in this
category include those undergoing abdominal pelvic surgery with a Caprini score >8,
patients with multiple risk factors, patients undergoing craniotomy or spinal surgery for
cancer, and patients with major trauma, especially that involving the brain or spine. (See
'With low bleeding risk: Combined prophylaxis' below.)
The efficacy of pharmacologic therapy in comparison with mechanical methods, and

specifically for LMW heparin compared with other anticoagulants is summarized below:
● Pharmacologic versus no prophylaxis or mechanical methods – In general,

randomized trials and meta-analyses have shown that pharmacologic prophylaxis with
LMW heparin, low-dose UFH, and fondaparinux are superior to placebo or mechanical
devices. However, in general, the level of support from data in patients at moderate risk
is weaker than for those at high risk.
• LMW heparin – In a meta-analysis of eight trials of five different preparations of

LMW heparin that included >48,000 general and abdominal surgery patients,
compared with no prophylaxis, LMW heparin reduced the risk of symptomatic VTE
by 70 percent but resulted in a doubling of the risk of major bleeding and wound
hematomas [18].
Similar results were obtained from another meta-analysis that also included
gastrointestinal, urologic, gynecologic, and thoracic surgery patients [145].
Trials reporting the efficacy of LMW heparin combined with compression stockings
in nonorthopedic patients including those undergoing neurosurgery are discussed
below. (See 'With low bleeding risk: Combined prophylaxis' below.)
• Low-dose UFH – An early trial involving over 4000 patients established the efficacy
of low-dose UFH for reducing the incidence of fatal PE in patients undergoing major
surgical procedures compared with controls (0.7 versus 0.1 percent) [107]. Pooled
data from meta-analyses subsequently confirmed that low-dose UFH reduced the
incidence of all DVT, proximal DVT, and all PE including fatal PE, when compared
with placebo [26,98,146,147].
● LMW heparin versus other agents – Our preference for LMW heparin is based upon
direct data derived from nonorthopedic surgical populations that included randomized
trials and meta-analyses, most of which show similar or superior efficacy compared
with UFH as well as indirect data that show similar benefits in orthopedic and medical
populations. However, the quality of data is limited by the heterogeneity of study
populations eg, (wide range in risk, different surgery types) and the failure to
distinguish symptomatic from asymptomatic VTE. (See "Prevention of venous
thromboembolism in adults undergoing hip fracture repair or hip or knee
replacement" and "Prevention of venous thromboembolic disease in acutely ill
hospitalized medical adults", section on 'Low molecular weight heparin'.)
● LMW heparin versus low-dose UFH – Low-dose UFH is generally considered an

alternative to LMW heparin, when, for example, cost or renal insufficiency is an issue.
While early meta-analyses comparing low-dose UFH and LMW heparin found similar
efficacy and safety for both agents [148,149], newer analyses suggest that LMW
heparin is superior. As an example, compared with low-dose UFH, one meta-analysis of
51 randomized trials of general surgery patients reported that the rate of VTE events
was 30 percent lower in patients receiving LMW heparin without any effect on death or
bleeding [18]. However, the same efficacy was not apparent when the analysis was
confined to placebo-controlled trials. Most of the patients in these trials underwent
abdominal (particularly for gastrointestinal disease) or thoracic surgery, but some
patients underwent gynecologic or urologic surgery, mastectomy, or vascular
procedures [26,146].
Similar results of superior or similar efficacy were reported in other meta-analyses and
randomized trials that included patients undergoing gynecologic and urologic surgery
[18,145,148-151], and cancer surgery [152-158].
For patients admitted with major trauma, LMW heparin was also reported to be
superior to UFH in the prevention of both total and proximal DVTs [27,159-161].
● Fondaparinux versus UFH or LMW heparin – Fondaparinux is an alternative to LMW

heparin and UFH in patients with contraindications to heparin (eg, HIT) or when these
agents are not available. In a randomized trial (PEGASUS) of 2408 patients undergoing
major abdominal surgery, fondaparinux and the LMW heparin, dalteparin, had a
similar efficacy in reducing the rate of VTE (4.4 versus 6.1 percent) without any
increased rate of major bleeding (3.4 versus 2.4 percent) [151]. In a meta-analysis that
pooled the results from this study with studies including orthopedic patients, when
compared with LMW heparin, fondaparinux did not reduce VTE events but resulted in
an increased risk of bleeding [9]. (See "Prevention of venous thromboembolism in
adults undergoing hip fracture repair or hip or knee replacement".)
● Oral agents (warfarin, aspirin, direct oral anticoagulants) – Although oral agents
including warfarin, aspirin, direct thrombin inhibitors (eg, dabigatran) and factor Xa
inhibitors (eg, rivaroxaban, edoxaban, and apixaban) are sometimes administered in
orthopedic patients for VTE prevention, they are unstudied and are not routinely
administered in nonorthopedic surgical patients. Occasionally, for patients undergoing
general or abdominal/pelvic surgery considered at high risk for VTE in whom LMW
heparin or UFH is contraindicated or unavailable, some experts administer aspirin as
an alternative to fondaparinux or mechanical methods, although the data to support
this strategy is indirect and derived from patients undergoing major orthopedic
surgery [12]. (See "Prevention of venous thromboembolism in adults undergoing hip
fracture repair or hip or knee replacement".)
With low bleeding risk: Combined prophylaxis — Combining pharmacologic and

mechanical methods of prophylaxis are generally reserved for those considered to be at the
highest risk of VTE. Although there are a paucity of high quality studies comparing combined
methods with pharmacologic prophylaxis alone, data in general suggest that combining
methods of thromboprophylaxis offers additional protective benefit against the
development of VTE. However, the contributions of each method is unclear and most studies
are limited by incomplete blinding, small sample size, uncertain concealment, and
measurement of surrogate outcomes. No convincing data report further benefits in efficacy
when two mechanical methods are combined or added to pharmacologic agents.
As examples:
● In a large meta-analysis of 34 trials, which included data on 14,931 patients (mixed

surgical, trauma, orthopedic), the addition of IPC to pharmacologic prophylaxis
reduced the incidence of PE from 1.8 to 0.9 percent (OR 0.46, 95% CI 0.30-0.71, low-
certainty evidence) and the incidence of DVT from 9.2 to 5.5 percent (OR 0.38, 95% CI
0.21-0.70, high-certainty evidence) [162]. The results did not appear to be biased by the
inclusion of orthopedic patients in the analysis, since combined prophylaxis resulted in
a similar reduction in PE and DVT in both orthopedic and nonorthopedic surgical
patients.
● In a meta-analysis of 25 randomized trials in mixed surgical populations, adding

pharmacologic agents to GCS almost halved the rate of postoperative DVT (RR 0.56)
while the risk of bleeding almost doubled (RR 1.74) compared with GCS alone [139]. In
another meta-analysis, rates of DVT were lower in those treated with GCS plus any
other prophylactic method compared with GCS alone (4 versus 13 percent) [138].
● Several randomized trials of patients undergoing neurosurgical procedures reported

LMW heparin, when added to GCS, prevented more venographic DVT than GCS alone
(17 to 19 percent versus 26 to 32 percent) without an increased risk of bleeding
[163,164].
● In a randomized trial (APOLLO) of patients undergoing major abdominal surgery

(gastrointestinal, urologic), fondaparinux combined with IPC significantly reduced the
rate of VTE when compared with IPC alone (1.7 versus 5.3 percent) [165]. Major
bleeding was more frequent after fondaparinux (1.6 versus 0.2 percent), although none
of the bleeding events were fatal or involved a critical organ.
● In a "quasi"-randomized trial (IPC SUPER) of patients undergoing major surgery and a

Caprini score of ≥9, standard care (low molecular weight heparin plus antiembolism
stockings) combined with IPC reduced the rate of asymptomatic DVT (0.5 versus 16.7
percent) compared with standard care alone [166]. However, limitations including lack
of blinding and the inclusion of asymptomatic VTE as an endpoint prohibit firm
conclusions.
With high bleeding risk: Mechanical methods — For patients with contraindications to

pharmacologic prophylaxis (eg, active bleeding, intracranial hemorrhage, bleeding diathesis
( table 3)), patients at high risk of bleeding, or patients in whom the consequences of
bleeding are thought to be potentially catastrophic (eg, neurosurgical procedures), we
suggest mechanical methods rather than no thromboprophylaxis. Among the options, IPC is
the typical method used but data to support their use over graduated compression
stockings or VFP devices are limited. Vena cava filters should not be routinely used for VTE
prevention. (See 'Intermittent pneumatic compression and venous foot pump' above and
'Methods not recommended' below.)
Switching to or adding a pharmacologic agent, such as LMW heparin, should be done as

soon as the bleeding risk becomes acceptably low (eg, 48 to 72 hours following
neurosurgery) or the bleeding diathesis has been reversed. (See 'Assess risk for major
bleeding' above.)
SPECIFIC SURGICAL POPULATIONS
Additional data that support VTE prophylaxis in special surgical populations are discussed
separately in the followings topics:
General and abdominal/pelvic surgery
● Bariatric surgery ( table 4) (see "Bariatric surgery: Postoperative and long-term

management of the uncomplicated patient", section on 'Venous thromboembolism')
● Colon surgery (see "Overview of colon resection", section on 'Thromboprophylaxis')
● Abdominal aortic aneurysm repair (see "Open surgical repair of abdominal aortic
aneurysm", section on 'Thromboprophylaxis' and "Endovascular repair of abdominal
aortic aneurysm", section on 'Thromboprophylaxis')
● Extremity amputation (see "Lower extremity amputation", section on

'Thromboprophylaxis' and "Upper extremity amputation", section on 'Evaluation and
preparation')
● Gynecologic surgery (see "Overview of preoperative evaluation and preparation for

gynecologic surgery", section on 'Thromboprophylaxis')
Neurosurgery including neurotrauma
● Traumatic brain injury (see "Management of acute moderate and severe traumatic
brain injury", section on 'Venous thromboembolism prophylaxis')
● Spinal cord injury (see "Respiratory complications in the adult patient with chronic
spinal cord injury", section on 'Venous thromboembolism')
● Surgery for brain tumors (see "Treatment and prevention of venous thromboembolism
in patients with brain tumors", section on 'Primary prevention (VTE prophylaxis)')
Anesthesia and perioperative care
● Patients undergoing neuraxial anesthesia or analgesia (see "Neuraxial

anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet
medication" and "Perioperative management of patients receiving anticoagulants",
section on 'Neuraxial anesthesia')
● Critically ill patients including postoperative surgical patients (see "Prevention of

venous thromboembolic disease in acutely ill hospitalized medical adults", section on
'Selection of method of prophylaxis')
● Trauma patients (see "Venous thromboembolism risk and prevention in the severely
injured trauma patient", section on 'Thromboprophylaxis')
● Patients with stroke (see "Prevention and treatment of venous thromboembolism in

patients with acute stroke")
● Patients with cancer ( table 5) (see "Risk and prevention of venous thromboembolism
in adults with cancer")
● Patients who are pregnant (see "Deep vein thrombosis and pulmonary embolism in
pregnancy: Prevention")
ADMINISTRATION
Timing of initiation — The optimal timing for initiation of mechanical and/or

pharmacologic thromboprophylaxis in nonorthopedic patients is unknown and should be
individualized according to factors including timing of surgery (elective or emergency), type
and duration of surgery, the estimated risk of bleeding, and baseline risk of VTE. (See 'Assess
risk for thrombosis' above and 'Assess risk for major bleeding' above.)
Studies that specifically examine timing of pharmacologic dosing are limited. However, the
approach below is in accordance with studies that proved efficacy of pharmacologic agents
(see 'Pharmacologic dosing' below), as well as data derived from observational studies in
trauma patients (ie, patients with the highest risk of VTE and bleeding). (See "Venous
thromboembolism risk and prevention in the severely injured trauma patient", section on
'Specific trauma populations'.)
For most patients in whom thromboprophylaxis is indicated and the risk of bleeding is low,
experts agree that mechanical methods may commence just before surgery and that
pharmacologic agents should ideally commence within 2 to 12 hours preoperatively. The
exception to this rule is fondaparinux, which is typically started six to eight hours after skin
closure. In patients not considered suitable candidates for preoperative pharmacologic
thromboprophylaxis due to a contraindication to anticoagulants, a high risk of bleeding, or
potential catastrophic effect of bleeding, mechanical methods should be employed (typically
just before surgery) and pharmacologic agents started or added postoperatively, as soon as
hemostasis is achieved and it is considered safe (eg, 2 to 72 hours).
All anticoagulants have a boxed warning regarding the risk of spinal or epidural hematoma
in patients receiving neuraxial anesthesia or undergoing spinal puncture. The risk is
increased in those with indwelling epidural catheters, other drugs that impair hemostasis
(eg, anti-platelet agents), traumatic or repeated epidural or spinal puncture, or a history of
spinal surgery. Evidence-based guidelines from the American Society of Regional Anesthesia
(ASRA) are discussed separately. (See "Neuraxial anesthesia/analgesia techniques in the
patient receiving anticoagulant or antiplatelet medication" and "Perioperative management
of patients receiving anticoagulants", section on 'Neuraxial anesthesia' and "Overview of
neuraxial anesthesia", section on 'Spinal-epidural hematoma (SEH)'.)
Perioperative management of anticoagulants for patients who are therapeutically

anticoagulated is discussed separately. (See "Perioperative management of patients
receiving anticoagulants".)
Duration — In most cases VTE prophylaxis is continued until the patient becomes fully
ambulatory or until hospital discharge (typically up to 10 days). Once patients become fully
ambulatory, pharmacologic and mechanical methods of prophylaxis are generally stopped.
However, the definition of ambulatory is highly subjective such that patients who have
prolonged periods of immobility in between ambulatory periods should probably receive
continued or additional methods of prophylaxis, particularly in light of the fact that the risk
of VTE does not drop to zero upon ambulation but rather may be sustained for weeks
beyond the day of surgery [167]. In addition, 10 to 14 days of thromboprophylaxis may be
indicated in high-risk surgical patients, including those with cancer. (See "Risk and
prevention of venous thromboembolism in adults with cancer", section on 'Surgical
patients'.)
Extended pharmacologic VTE prophylaxis beyond discharge is not routinely recommended

in most nonorthopedic surgical patients except for those who undergo major abdominal
and/or pelvic surgery for cancer. Extended pharmacologic VTE prophylaxis, typically with low
molecular weight (LMW) heparin, is offered to this population who are at very high risk for
VTE for four weeks postdischarge. The optimal duration of extended prophylaxis is unknown
but is typically recommended beyond 10 days and for a period of three to four weeks for
high-risk patients who undergo major abdominal and/or pelvic surgery for cancer [12,152-
154,168-170]. (See "Risk and prevention of venous thromboembolism in adults with cancer",
section on 'Surgical patients'.)
Several meta-analyses of randomized and nonrandomized trials have demonstrated benefit

associated with extended prophylaxis in major abdominal/pelvic surgery, particularly for
cancer [28,152,154,168,171-173]. As an example, in a meta-analysis of seven randomized
trials of patients undergoing major abdominal or pelvic surgery, extended prophylaxis with
low molecular weight heparin resulted in a reduction in the overall rate of VTE (5 versus 13
percent) and rate of symptomatic VTE (1 versus 0.1 percent) without an increased risk of
bleeding (4 versus 3 percent) [173]. Oral rivaroxaban has been shown to be effective
compared with placebo in the extended duration setting among patients who undergo
laparoscopic resection for colorectal cancer [174].
Pharmacologic dosing — Pharmacologic prophylaxis is the method of choice for surgical

patients at moderate or high risk for VTE (Caprini score ≥3) ( table 1). Efficacy is discussed
above. (See 'Moderate or high VTE risk' above.)
Low molecular weight heparin — In general, LMW heparin is pharmacologic agent of

choice for preventing VTE in nonorthopedic surgical patients. (See 'With low bleeding risk:
Pharmacologic alone' above.)
A number of LMW heparin preparations are available (enoxaparin, dalteparin, tinzaparin,

nadroparin) none of which have proven superiority over the others when administered as
agents to prevent VTE. These regimens differ in detail from product label recommendations
but are generally consistent with 2012 American College of Chest Physicians (ACCP)
guidelines on antithrombotic therapy and 2013 guidelines of the American Society of Clinical
Oncology on VTE prophylaxis and treatment in patients with cancer [12,169].
Typical regimens commonly used in nonorthopedic surgical patients (assuming no renal

insufficiency at any point) are listed below. Considerations for individualizing therapy,
including adjustments required for neuraxial (ie, epidural or spinal) anesthesia, are reviewed
elsewhere. (See 'Timing of initiation' above and 'Duration' above.)
● Enoxaparin:
• Patients without cancer – 40 mg subcutaneously once daily started two hours

before abdominal surgery or about 12 hours before other surgery and 40 mg once
daily thereafter. Alternatively, 40 mg once daily started within 24 hours after surgery
once hemostasis is achieved and initiation is considered safe.
• Patients with cancer – 40 mg 10 to 12 hours before surgery and 40 mg once daily

thereafter [169]. Alternatively, 40 mg once daily started approximately 12 to 24
hours after surgery. There is variation in clinical practice especially with regards to
the administration of enoxaparin before surgery in patients with cancer. (See "Risk
and prevention of venous thromboembolism in adults with cancer", section on
'Surgical patients'.)
• Both once daily and twice daily regimens of enoxaparin have been shown to be
effective but direct comparison of these regimens are poorly studied [159]. More
aggressive prophylaxis (eg, twice daily enoxaparin and/or the addition of a
mechanical device) may be considered in very high-risk populations (eg, patients

with cancer).
● Dalteparin:
• Including patients with cancer – 5000 units subcutaneously started about 12 hours
(or evening) before surgery and 5000 units once daily thereafter.
• Although labeling in some countries recommends reduced doses in lower

thrombotic risk general surgeries (2500 units subcutaneously started 1 to 2 hours
before surgery and 2500 units daily thereafter), we use full dosing listed above
when LMW prophylaxis is indicated.
Less commonly used agents are:
● Tinzaparin (not available in the United States):
• Including patients with cancer – 4500 units subcutaneously started 12 hours before
surgery and once daily thereafter. An alternative weight-based regimen is listed in
the drug information monograph.

thrombotic risk general surgeries (3500 units subcutaneously started one to two
hours before surgery and 3500 units daily thereafter), we use full dosing listed
above when LMW prophylaxis is indicated.
● Nadroparin (not available in the United States):
• High VTE risk including patients with cancer – 38 units/kg (maximum 3800 units)
subcutaneously once daily started 12 hours before surgery; on postoperative day 4
increase dose to 57 units/kg (maximum 5700 units once daily).

thrombotic risk general surgeries (2850 units subcutaneously started one to two
hours before surgery and 2850 units daily thereafter), we use full dosing listed
above when LMW prophylaxis is indicated.
The platelet count should be monitored regularly (eg, day 5, 7, and 9) in all patients receiving
LMW heparin to detect the development of heparin-induced thrombocytopenia (HIT). All
heparin agents are contraindicated in patients with active HIT or a history of HIT, the details
of which are discussed separately. (See "Management of heparin-induced
thrombocytopenia".)
The ideal dose for patients with obesity is unknown. In patients with a BMI ≥40 kg/m2, some
experts empirically increase the standard LMW heparin dose by approximately 30 percent
[175]. Suggested doses for patients with obesity and patients undergoing bariatric surgery
are presented in the table ( table 4) and discussed separately. (See "Bariatric surgery:
Postoperative and long-term management of the uncomplicated patient", section on
'Venous thromboembolism'.)
Based upon data extrapolated from patients receiving therapeutic doses of LMW heparin,
we prefer the avoidance of these agents in patients with severe renal insufficiency (eg,
creatinine clearance 20 to 30 mL/min and end stage renal failure requiring dialysis) should it
be present upon admission. For those with mild renal insufficiency dose-adjustments can be
made according to the creatinine clearance and agent chosen, as outlined in the table
( table 2). For those who develop severe renal insufficiency during hospitalization, it is
prudent that the LMW heparin agent be discontinued and replaced with unfractionated
heparin (UFH). (See "Heparin and LMW heparin: Dosing and adverse effects".)
Low-dose unfractionated heparin — Low-dose UFH is generally considered an alternative

to LMW heparin, when, for example, cost or renal insufficiency (creatinine clearance <20 to
30 mL/min) is an issue.
Low-dose subcutaneous UFH for VTE prophylaxis is usually given as 5000 units every 12
hours starting two or more hours before surgery.
Occasionally, if the risk is assessed as particularly high, the frequency is increased to three
times daily, although data to support this dosing is lacking. In patients with cancer, 5000
units every eight hours starting two to four hours before surgery is suggested by American
Society of Clinical Oncology 2013 guidelines [169]. Factors including cost, institutional policy,
body weight, and risk of bleeding may be used to help the clinician make the decision to
choose the frequency of dosing.
The ideal dose for patients with obesity is unknown such that dosing should be
individualized on a case-by-case basis. We generally prefer to empirically treat with UFH
5000 to 7500 units twice daily; alterations in the dosing and frequency (eg, three times
per day dosing) should be tailored to individual patients [176-178].
The dose of UFH does not need to be adjusted for patients with renal insufficiency. However,
similar to LMW heparin, the platelet count should be monitored regularly (eg, day 5, 7, and
9) to detect the development of HIT, in which case UFH should be discontinued. (See
"Heparin and LMW heparin: Dosing and adverse effects", section on 'Platelet count
monitoring'.)
Fondaparinux — Fondaparinux is an alternative to LMW heparin and UFH in patients with

contraindications to heparin (eg, HIT) or when these agents are not available.
Unlike LMW heparin agents, which are often administered pre and postoperatively, in
accordance with trials that have shown benefit, fondaparinux is typically given as 2.5 mg
once daily, starting at least six to eight hours postoperatively (after skin closure). Although in
Europe, a 1.5 mg dose is suggested for individuals with creatinine clearance of 20 to 50
mL/min, the safety and efficacy of this dose has not been well-studied. One systematic
review of 17 trials reported superior efficacy of fondaparinux compared with LMW heparin
(odds ratio [OR] 0.49; 95% CI 0.38-0.64) but at the expense of an increased risk of major
bleeding (OR 1.48, 95% CI 1.15-1.9) [179]. Dosing and adverse effects of fondaparinux are
discussed separately. (See "Fondaparinux: Dosing and adverse effects".)
METHODS NOT RECOMMENDED
Screening — Secondary prevention with screening tests targeted at the early detection of

thrombosis (eg, ultrasonography) is not recommended but can be reserved for rare patients
in whom primary prophylaxis is not suitable (eg, patients with active minor bleeding); in such
cases, resumption of primary prophylaxis should be performed as soon as is feasible
[180,181]. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized
medical adults", section on 'Definition of VTE prophylaxis' and "Overview of inpatient
management of the adult trauma patient", section on 'Screening for venous
thromboembolism'.)
Prophylactic vena cava filters — Inferior vena cava (IVC) filters should generally be avoided
as prophylaxis against postoperative VTE. This approach is best supported by indirect
evidence from large populations of medical and surgical patients (PREPIC) in whom IVC
filters were placed (mostly for therapy) that reported a reduction in pulmonary embolism
(PE) but an increase in the rate of lower extremity deep venous thrombosis (DVT). These data
are discussed separately. (See "Overview of the treatment of proximal and distal lower
extremity deep vein thrombosis (DVT)", section on 'Inferior vena cava filter'.)
Smaller observational studies have confirmed similar outcomes in surgical patients:
● One retrospective study of over 6000 bariatric patients reported that compared with
those who did not receive an IVC filter, filter placement did not reduce the rate of VTE
and may be associated with an increased risk of death or serious disability [182].
● Systematic reviews and observational studies in trauma patients reported a reduction

in the rate of PE but increased rate of DVT and IVC filter complications (eg, migration)
without an effect on mortality in those treated with an IVC filter compared with those in
whom a filter was not placed [183-185]. In contrast, another randomized study
reported no difference in DVT or PE rate in trauma patients with who had an early
prophylactic IVC filter placed compared with those who did not have a filter placed
[186]. These data are discussed separately. (See "Venous thromboembolism risk and
prevention in the severely injured trauma patient".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Superficial vein
thrombosis, deep vein thrombosis, and pulmonary embolism".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Beyond the Basics topics (see "Patient education: Deep vein thrombosis (DVT) (Beyond
the Basics)" and "Patient education: Warfarin (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● Defining the population – Postoperative venous thromboembolism (VTE) is common

among patients undergoing nonorthopedic surgery. This population includes patients
undergoing general and abdominal-pelvic surgery, bariatric, vascular,
plastic/reconstructive, cardiac, and thoracic surgery as well as patients undergoing
neurosurgery and patients admitted with major trauma. (See 'Introduction' above.)
● Assess thrombosis risk – The risk of postoperative VTE depends upon procedure-
related factors (eg, anatomic location, degree of invasiveness, type and duration of
anesthesia, requirement for postoperative immobilization) and patient-related risk

factors (eg, increasing age, prior VTE, presence of malignancy) all of which need to be
assessed prior to surgery so that a risk category can be assigned and method
appropriately selected. (See 'Assess risk for thrombosis' above.)
• For patients undergoing general (eg, breast, thyroid, parathyroid) and abdominal-
pelvic (gastrointestinal, urologic, gynecologic) surgery as well as patients
undergoing bariatric, vascular, and plastic/reconstructive surgery, the modified
Caprini risk assessment score is used to classify patient into very low risk, low risk,
moderate risk, and high risk ( table 1).
• Patients undergoing major cardiac, thoracic, brain, and spinal surgery or patients
with major trauma are at minimum, moderate risk for VTE (eg, uncomplicated
cardiac, bariatric, minor thoracic or spinal surgery) and many are at high risk for VTE
(eg, craniotomy, extensive cardiac or thoracic surgery, spinal surgery for
malignancy, trauma involving brain or spine). (See 'Assess risk for thrombosis'
above.)
● Suggested approach based upon VTE risk – In nonorthopedic patients, assuming the
risk of bleeding is low, we suggest the following approach ( table 1):
• Very low risk – For most patients at very low risk of VTE, pharmacologic or
mechanical methods of thromboprophylaxis are typically not necessary since most
are fully ambulatory; thus, early and frequent ambulation is the preferred method in
this population. (See 'Very low thrombosis risk: Early ambulation' above.)
• Low risk – For patients at low risk of VTE, we suggest mechanical methods of VTE
prophylaxis, rather than pharmacologic or no thromboprophylaxis (Grade 2C).
Choosing among mechanical methods is individualized, but intermittent pneumatic
compression (IPC) devices or graduated compression stockings (GCS) are frequently
chosen. (See 'Low VTE risk: Mechanical methods' above.)
• Moderate risk – For patients at moderate risk of VTE, we suggest pharmacologic

prophylaxis, preferably with low molecular weight (LMW) heparin, rather than no
thromboprophylaxis (Grade 2B). (See 'Moderate or high VTE risk' above and
'Pharmacologic dosing' above.)
• High risk – For patients at high risk of VTE, we recommend, at minimum,

pharmacologic prophylaxis, preferably with LMW heparin, rather than mechanical
methods or no prophylaxis (Grade 1B). Combining pharmacologic with mechanical
methods of thromboprophylaxis is frequently performed in this population
especially in those at greatest risk (eg, multiple risk factors or cancer). (See
'Moderate or high VTE risk' above.)
• High bleeding risk – For nonorthopedic surgical patients with contraindications to

pharmacologic prophylaxis and in whom thromboprophylaxis other than
ambulation is indicated ( table 3), patients with active or at high risk of bleeding
or patients in whom the consequences of bleeding are thought to be potentially
catastrophic (eg, neurosurgical procedures), mechanical methods rather than no
thromboprophylaxis are preferred. IPC devices are commonly used, but GCS or
venous foot pump devices are also appropriate ( picture 1 and picture 2).
Switching to or adding a pharmacologic agent, such as LMW heparin, should be
done as soon as the bleeding risk becomes acceptably low (eg, 48 to 72 hours
following neurosurgery) or the bleeding diathesis has been reversed.
• Renal insufficiency – For most patients without renal insufficiency (eg, creatinine
clearance >30 mL/min) in whom pharmacologic prophylaxis is indicated, we suggest
LMW heparin rather than unfractionated heparin (UFH) ( table 2) (Grade 2C). UFH
is preferred in those with severe renal insufficiency (eg, creatinine clearance <20 to
30 mL/min), while fondaparinux is preferred in those with heparin-induced
thrombocytopenia. Oral agents including warfarin, aspirin, and direct oral
anticoagulants are unstudied and are not typically administered in nonorthopedic
surgical patients. (See 'With low bleeding risk: Pharmacologic alone' above.)
● Timing – The optimal timing for initiation of thromboprophylaxis is unknown and

should be individualized.
• For most patients in whom the bleeding risk is low, mechanical methods are ideally
started just before surgery and pharmacologic agents administered within 2 to 12
hours before surgery, with the exception of fondaparinux, which is typically initiated
6 to 8 hours after skin closure. Postoperatively, thromboprophylaxis is started within
24 hours of surgery, typically on the evening of the day of surgery (6 to 8 hours
postoperatively) or on the morning of the day after surgery. (See 'Timing of
initiation' above.)
• However, in patients with a contraindication to anticoagulants, a high risk of

bleeding, or potential catastrophic effect of bleeding, mechanical methods should
be employed postoperatively and pharmacologic agents started or added
postoperatively, when adequate hemostasis is achieved and it is assessed as safe
(eg, after 48 to 72 hours).
● Duration – In most patients, we suggest that VTE prophylaxis be continued until the
patient becomes fully ambulatory or until hospital discharge. Extended pharmacologic
VTE prophylaxis beyond discharge is not routinely recommended in this population

except for patients who undergo major abdominal and/or pelvic surgery for cancer in
whom thromboprophylaxis should be continued for a period of four weeks. (See
'Duration' above.)
ACKNOWLEDGMENT
The UpToDate editorial staff acknowledges Menaka Pai, MD, FRCPC, who contributed to
earlier versions of this topic review.
Use of UpToDate is subject to the Terms of Use.
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twice-daily enoxaparin for venous thromboembolism prophylaxis in high-risk trauma
patients. J Intensive Care Med 2011; 26:111.
160. Jacobs BN, Cain-Nielsen AH, Jakubus JL, et al. Unfractionated heparin versus low-
molecular-weight heparin for venous thromboembolism prophylaxis in trauma. J
Trauma Acute Care Surg 2017; 83:151.
161. Byrne JP, Geerts W, Mason SA, et al. Effectiveness of low-molecular-weight heparin
versus unfractionated heparin to prevent pulmonary embolism following major trauma:
A propensity-matched analysis. J Trauma Acute Care Surg 2017; 82:252.
162. Kakkos S, Kirkilesis G, Caprini JA, et al. Combined intermittent pneumatic leg
thromboembolism. Cochrane Database Syst Rev 2022; 1:CD005258.
163. Agnelli G, Piovella F, Buoncristiani P, et al. Enoxaparin plus compression stockings
compared with compression stockings alone in the prevention of venous
thromboembolism after elective neurosurgery. N Engl J Med 1998; 339:80.
164. Nurmohamed MT, van Riel AM, Henkens CM, et al. Low molecular weight heparin and
compression stockings in the prevention of venous thromboembolism in neurosurgery.
Thromb Haemost 1996; 75:233.
165. Turpie AG, Bauer KA, Caprini JA, et al. Fondaparinux combined with intermittent
pneumatic compression vs. intermittent pneumatic compression alone for prevention of
venous thromboembolism after abdominal surgery: a randomized, double-blind
comparison. J Thromb Haemost 2007; 5:1854.
166. Lobastov K, Sautina E, Alencheva E, et al. Intermittent Pneumatic Compression in
Addition to Standard Prophylaxis of Postoperative Venous Thromboembolism in
Extremely High-risk Patients (IPC SUPER): A Randomized Controlled Trial. Ann Surg 2021;
274:63.
167. Amin AN, Girard F, Samama MM. Does ambulation modify venous thromboembolism
risk in acutely ill medical patients? Thromb Haemost 2010; 104:955.
168. Kakkar VV, Balibrea JL, Martínez-González J, et al. Extended prophylaxis with bemiparin
for the prevention of venous thromboembolism after abdominal or pelvic surgery for
cancer: the CANBESURE randomized study. J Thromb Haemost 2010; 8:1223.
169. Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and
treatment in patients with cancer: American Society of Clinical Oncology clinical practice
guideline update. J Clin Oncol 2013; 31:2189.
170. Streiff MB, Bockenstedt PL, Cataland SR, et al. Venous thromboembolic disease. J Natl
Compr Canc Netw 2011; 9:714.
171. Bottaro FJ, Elizondo MC, Doti C, et al. Efficacy of extended thrombo-prophylaxis in major
abdominal surgery: what does the evidence show? A meta-analysis. Thromb Haemost
2008; 99:1104.
172. Rausa E, Kelly ME, Asti E, et al. Extended versus conventional thromboprophylaxis after
major abdominal and pelvic surgery: Systematic review and meta-analysis of
randomized clinical trials. Surgery 2018; 164:1234.
173. Felder S, Rasmussen MS, King R, et al. Prolonged thromboprophylaxis with low
molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev
2019; 3:CD004318.
174. Becattini C, Pace U, Pirozzi F, et al. Rivaroxaban vs placebo for extended antithrombotic
prophylaxis after laparoscopic surgery for colorectal cancer. Blood 2022; 140:900.
175. Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Low-molecular-weight heparins in
renal impairment and obesity: available evidence and clinical practice recommendations
across medical and surgical settings. Ann Pharmacother 2009; 43:1064.
176. Joy M, Tharp E, Hartman H, et al. Safety and Efficacy of High-Dose Unfractionated
Heparin for Prevention of Venous Thromboembolism in Overweight and Obese
Patients. Pharmacotherapy 2016; 36:740.
177. Wang TF, Milligan PE, Wong CA, et al. Efficacy and safety of high-dose
thromboprophylaxis in morbidly obese inpatients. Thromb Haemost 2014; 111:88.
178. Samuel S, Iluonakhamhe EK, Adair E, et al. High dose subcutaneous unfractionated
heparin for prevention of venous thromboembolism in overweight neurocritical care
patients. J Thromb Thrombolysis 2015; 40:302.
179. Kumar A, Talwar A, Farley JF, et al. Fondaparinux Sodium Compared With Low-Molecular-
Weight Heparins for Perioperative Surgical Thromboprophylaxis: A Systematic Review
and Meta-analysis. J Am Heart Assoc 2019; 8:e012184.
180. Meyer CS, Blebea J, Davis K Jr, et al. Surveillance venous scans for deep venous
thrombosis in multiple trauma patients. Ann Vasc Surg 1995; 9:109.
181. Schellong SM, Beyer J, Kakkar AK, et al. Ultrasound screening for asymptomatic deep
vein thrombosis after major orthopaedic surgery: the VENUS study. J Thromb Haemost
2007; 5:1431.
182. Birkmeyer NJ, Share D, Baser O, et al. Preoperative placement of inferior vena cava
filters and outcomes after gastric bypass surgery. Ann Surg 2010; 252:313.
183. Girard TD, Philbrick JT, Fritz Angle J, Becker DM. Prophylactic vena cava filters for trauma
patients: a systematic review of the literature. Thromb Res 2003; 112:261.
184. Rajasekhar A, Lottenberg R, Lottenberg L, et al. Pulmonary embolism prophylaxis with

inferior vena cava filters in trauma patients: a systematic review using the meta-analysis
of observational studies in epidemiology (MOOSE) guidelines. J Thromb Thrombolysis
2011; 32:40.
185. Hemmila MR, Osborne NH, Henke PK, et al. Prophylactic Inferior Vena Cava Filter
Placement Does Not Result in a Survival Benefit for Trauma Patients. Ann Surg 2015;
262:577.
186. Ho KM, Rao S, Honeybul S, et al. A Multicenter Trial of Vena Cava Filters in Severely
Injured Patients. N Engl J Med 2019; 381:328.
Topic 1339 Version 113.0
GRAPHICS
Modified Caprini risk assessment model for VTE in general surgical

patients
Risk score
1 point 2 points 3 points 5 points
Age 41 to 60 years Age 61 to 74 years Age ≥75 years Stroke (<1 month)
Minor surgery Arthroscopic surgery History of VTE Elective arthroplasty
BMI >25 kg/m 2 Major open surgery Family history of VTE Hip, pelvis, or leg
(>45 minutes) fracture
Swollen legs Laparoscopic surgery Factor V Leiden Acute spinal cord

(>45 minutes) injury (<1 month)
Varicose veins Malignancy Prothrombin 20210A
Pregnancy or Confined to bed (>72 Lupus anticoagulant

postpartum hours)
History of Immobilizing plaster Anticardiolipin

unexplained or cast antibodies
recurrent
spontaneous abortion
Oral contraceptives or Central venous access Elevated serum

hormone replacement homocysteine
Sepsis (<1 month) Heparin-induced

thrombocytopenia
Serious lung disease, Other congenital or

including pneumonia acquired
(<1 month) thrombophilia
Abnormal pulmonary
function
Acute myocardial
infarction
Congestive heart
failure (<1 month)
History of
inflammatory bowel
disease
Medical patient at bed

rest
Interpretation
Estimated VTE risk

in the absence of
Surgical risk pharmacologic or
Score
category* mechanical
prophylaxis
(percent)
Very low (see text for 0 <0.5

definition)
Low 1 to 2 1.5
Moderate 3 to 4 3.0
High ≥5 6.0
VTE: venous thromboembolism; BMI: body mass index.
* This table is applicable only to general, abdominal-pelvic, bariatric, vascular, and plastic and
reconstructive surgery. See text for other types of surgery (eg, cancer surgery).
From: Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic
therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practical
guidelines. Chest 2012; 141:e227S. Copyright © 2012. Reproduced with permission from the American College of Chest
Physicians.
Graphic 83739 Version 14.0
Intermittent pneumatic compression device
Image courtesy of ArjoHuntleigh, Inc.
Venous foot pump
Representative image of a venous foot pump device that includes the pump, tubing, and two foot wraps
Courtesy of Medtronic. A-V Impulse is a trademark of a Medtronic company. © 2014 Covidien.
Suggested dose adjustments of low molecular weight (LMW) heparins in

adults with renal insufficiency
VTE treatment VTE prophylaxis*
Enoxaparin CrCl ≥30 mL/min: No adjustment CrCl ≥30 mL/min: No adjustment
CrCl <30 mL/min: Reduce to 1 mg/kg CrCl <30 mL/min: Reduce to 30 mg

once daily once daily (medical or surgical
patients)
Dalteparin CrCl ≥30 mL/min: No adjustment CrCl ≥30 mL/min: No adjustment
CrCl <30 mL/min: Use an

anticoagulant with less dependence
on renal clearance ¶
Nadroparin CrCl ≥50 mL/min: No adjustment CrCl ≥50 mL/min: No adjustment
(not available in CrCl 30 to 50 mL/min: Reduce dose CrCl 30 to 50 mL/min: Reduce dose
the US) by 25 to 33% if clinically warranted by 25 to 33% if clinically warranted
CrCl <30 mL/min: Contraindicated CrCl <30 mL/min: Reduce dose by 25

to 33%
Tinzaparin CrCl ≥30 mL/min: No adjustment CrCl ≥30 mL/min: No adjustment
(not available in CrCl <30 mL/min: Use with caution, CrCl <30 mL/min: Use with caution,
the US) although evidence suggests no although evidence suggests no
accumulation with CrCl as low as 20 accumulation with CrCl as low as 20
mL/min mL/min
Suggested dose adjustment of LMW heparins for reduced renal function (subcutaneous dosing).
Caution should be used in all patients with renal insufficiency, and all patients should be
observed for signs of bleeding. Accumulation may occur with repeated doses. An alternative
anticoagulant such as unfractionated heparin may be preferred, especially for individuals with
CrCl <30 mL/min, with renal failure, or receiving dialysis. Examples of alternatives include: [1]
Unfractionated heparin
An LMW heparin with lower renal clearance
A DOAC with low renal clearance (apixaban, renal clearance approximately 25%)
Use of LMW heparin in patients with renal insufficiency has been associated with hyperkalemia.
Refer to the UpToDate topics on the use of heparin and LMW heparin in specific clinical
conditions, for infants and children, and for acute coronary syndromes and myocardial infarction
(for which there are separate tables).
VTE: venous thromboembolism; CrCl: creatinine clearance as determined by Cockcroft-Gault

equation (a calculator is available in UpToDate); US: United States; LMW heparin: low molecular
weight heparin; DOAC: direct oral anticoagulant.
* Applies to short-term VTE prophylaxis (up to 10 days). For long-term use, periodic anti-factor Xa
activity testing may be useful to rule out drug accumulation.
¶ May consider checking anti-factor Xa activity, consistent with some authorities; [2-4] however,
ranges have not been established from clinical trials and no dose adjustment nomograms have
been clinically validated. Other experts and a 2018 guideline from the American Society of
Hematology recommend against checking anti-factor Xa activity and suggest dose adjustments
based on information in the product labeling or switching to an alternative anticoagulant such as
those listed above. If monitored, levels should be measured 4 to 6 hours after dosing, following
at least the third or fourth dose. Δ
Δ The following represent peak (4 hours after the dose) expected on-therapy values for
therapeutic dosing (for VTE) for anti-factor Xa activity, although these have not been clinically
validated: [1,2]
Enoxaparin twice daily: 0.6 to 1.0 anti-factor Xa units/mL (range, 0.5 to 1.5 [5] )
Enoxaparin once daily: >1.0 anti-factor Xa units/mL
Dalteparin once daily: 1.05 anti-factor Xa units/mL (range, 0.5 to 1.5 [6] )
Nadroparin once daily: 1.3 anti-factor Xa units/mL [7]
Tinzaparin once daily: 0.85 anti-factor Xa units/mL [8]
Data from:
1. Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of
venous thromboembolism: optimal management of anticoagulation therapy. Blood Advances 2018; 3257.
2. Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic therapy and prevention of
thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;
141:e24S.
3. Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Low-molecular-weight heparins in renal impairment and obesity:
Available evidence and clinical practice recommendations across medical and surgical settings. Ann
Pharmacother 2009; 43:1064.
4. Lexicomp Online. Copyright © 1978-2023 Lexicomp, Inc.
5. Enoxaparin sodium injection. US FDA approved prescribing information (revised October, 2013). Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020164s102lbl.pdf.
6. Dalteparin sodium injection. US FDA approved prescribing information (revised May, 2019). Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020287s072lbl.pdf.
7. Nadroparin calcium injection. Canada product monograph (revised January 2019). Available at:
https://pdf.hres.ca/dpd_pm/00049107.PDF.
8. Tinzaparin sodium injection. Canada product monograph (May 26, 2017). Available at:
https://pdf.hres.ca/dpd_pm/00040736.PDF.
Possible contraindications to anticoagulation
Possible contraindication Factors to consider
Active, clinically significant Site and degree of bleeding (eg, nosebleeds and menses
bleeding generally are not a contraindication; active intracerebral
bleeding is almost always an absolute contraindication), interval
since bleeding stopped
Severe bleeding diathesis Nature, severity, and reversibility of bleeding diathesis
Severe thrombocytopenia Absolute platelet count, platelet count trend, and platelet

(platelet count <50,000/microL) function (eg, some individuals with ITP and a platelet count in
the range of 30,000 to 50,000 may tolerate anticoagulation if
needed)
Major trauma Site and extent of trauma, time interval since event (eg, for a
patient with a mechanical heart valve it may be appropriate to
anticoagulate sooner after trauma than a patient with a lesser
indication)
Invasive procedure or obstetric Type of procedure and associated bleeding risk, interval
delivery (recent, emergency, or between procedure and anticoagulation
planned)
Previous intracranial Time interval since hemorrhage and underlying cause (eg,
hemorrhage trauma or uncontrolled hypertension)
Intracranial or spinal tumor Site and type of tumor, other comorbidities
Neuraxial anesthesia Interval since spinal/epidural puncture or catheter

removal, other alternatives for anesthesia; traumatic
procedures are more concerning
Severe, uncontrolled Absolute blood pressure and blood pressure trend

hypertension
This list does not take the place of clinical judgment in deciding whether or not to administer an
anticoagulant. In any patient, the risk of bleeding from an anticoagulant must be weighed
against the risk of thrombosis and its consequences. The greater the thromboembolic risk, the
greater the tolerance for the possibility of bleeding and for shortening the time interval between
an episode of bleeding and anticoagulant initiation. Refer to UpToDate content on the specific
indication for the anticoagulant and the specific possible contraindication for discussions of
these risks.
ITP: immune thrombocytopenia.
Suggested doses of low molecular weight heparins in adult patients with

a high body mass index (BMI)
Product labeling on
VTE treatment VTE prophylaxis use in patients with
a high BMI
Enoxaparin* Use standard treatment BMI 30 to 39 kg/m 2 : Use Safety and efficacy of
dosing (ie, 1 mg/kg every standard prophylaxis prophylactic doses in
12 hours based on dosing (ie, 30 mg every patients with obesity
TBW). ¶ 12 hours or 40 mg once (BMI >30 kg/m 2 ) has not
daily). [2] Some experts been fully determined,
Once-daily dosing
use weight-based dosing and there is no
regimens of enoxaparin
(ie, 0.5 mg/kg based on consensus for dose
are not
TBW once or twice daily, adjustment. Observe
recommended. [1]
depending upon level of carefully for signs and
VTE risk). Δ [3,4] symptoms of VTE. [10]
BMI ≥40 kg/m 2 : Marginal increase

Empirically increase observed in mean anti-
standard prophylaxis factor Xa activity using
dose by 30% (ie, from 30 TBW and 1.5 mg/kg
mg every 12 hours to 40 once-daily dosing in
mg every 12 hours). ◊ [2] healthy persons with
Some experts use obesity (BMI 30 to
weight-based dosing (ie, 48 kg/m 2 ) compared
0.5 mg/kg based on TBW with healthy persons
once or twice daily, with lower BMI. [10]
depending upon level of
VTE risk). Δ [3-7]
High VTE-risk bariatric

surgery with BMI ≤50
kg/m 2 : 40 mg every 12
hours. § [8,9]
High VTE-risk bariatric

surgery with BMI >50
kg/m 2 : 60 mg every 12
hours. § [9]
Dalteparin Use standard treatment BMI 30 to 39 kg/m 2 : Use Cancer-associated VTE

dosing (ie, 200 units/kg standard prophylaxis treatment: Use TBW-
once daily based on TBW dosing (ie, 5000 units based dosing for patients
for the first month, once daily). [2] weighing up to 99 kg.
followed by 150 units/kg Use a maximum dose of
BMI ≥40 kg/m 2 :
TBW once daily for 18,000 units per day for
Empirically increase
subsequent months). ¶ ¥ patients weighing
standard prophylaxis
≥99 kg. ¶ ¥ [12]
May consider using 100 dose by 30% (ie, from
units/kg based on TBW 5000 units once daily to
every 12 hours for 6500 units once

patients weighing daily). Δ ◊ [2]
≥90 kg. [11]
The labeled indication in

the United States for
adult patients is
extended treatment of
cancer-associated
VTE. [12]
Nadroparin Use standard treatment BMI 30 to 39 kg/m 2 : For Safety and efficacy of
(not available dosing (ie, 171 anti-factor orthopedic surgery, use LMWHs in high-weight
in the United Xa units/kg once daily weight-based dosing (ie, (ie, >120 kg) patients has
States) based on TBW or 86 38 anti-factor Xa units/kg not been fully
units/kg every 12 hours once daily based on TBW determined.
based on TBW). ¶ ‡ increasing on Individualized clinical
postoperative day 4 to 57 and laboratory
anti-factor Xa units/kg monitoring is
once daily); for general recommended (Canada
surgery use standard product monograph). [13]
fixed dosing (ie, 2850
VTE treatment: Use TBW-
anti-factor Xa units once
based dosing for patients
daily); for medically ill
weighing up to 100 kg.
patients use standard
Use a maximum dose of
fixed dosing (ie, 5700
17,100 anti-Xa units per
anti-factor Xa units once
day for patients weighing
daily provided TBW
>100 kg. ¶ ‡ [13]
>70 kg). [2]
BMI ≥40 kg/m 2 : For

orthopedic surgery, use
weight-based dosing (ie,
38 anti-factor Xa units/kg
once daily based on TBW
increasing on
postoperative day 4 to 57
anti-factor Xa units/kg
once daily); for general
surgery, empirically
increase fixed dose by
~30% (ie, increase from
2850 to 3800 anti-factor
Xa units once daily); for
medically ill patients,
empirically increase fixed
dose by ~30% (ie,
increase from 5700 to
7400 anti-factor Xa units
once daily provided TBW
>70 kg). Δ ◊ [2]
Tinzaparin Use standard treatment BMI 30 to 39 kg/m 2 : For Safety and efficacy in
(not available dosing (ie, 175 anti-factor orthopedic surgery, use patients weighing >120
in the United Xa units/kg once daily weight-based kg has not been fully
States) based on TBW). ¶ prophylaxis dosing (ie, 50 determined.
or 75 anti-factor Xa Individualized clinical
units/kg based on TBW and laboratory
once daily); for general monitoring is
surgery and medically ill recommended (Canada
patients, use standard product monograph). [15]
fixed dosing (ie, 3500 or
4500 anti-factor Xa units
once daily depending
upon level of VTE risk). [2]
BMI ≥40 kg/m 2 : For

orthopedic surgery, use
weight-based
prophylaxis dosing (ie, 50
or 75 anti-factor Xa
units/kg based on TBW
once daily); for general
surgery and medically ill
patients, empirically
increase fixed dose by
30% (ie, increase from
3500 to 4500 anti-factor
Xa units once daily or
from 4500 to 6000 anti-
factor Xa units once daily
depending on level of
VTE risk). Δ ◊ [2]
Moderate to high VTE-

risk bariatric surgery,
extended postoperative
prophylaxis regimen:
According to a protocol
evaluated at one center:
Beginning on
postoperative day 1: 75
units/kg based on TBW
once daily for 10 days;
patients weighing <110
kg received 4500 units
once daily; patients
weighing ≥160 kg
received 14,000 units
once daily. Δ § [14]
All doses shown are for patients with normal kidney function and are for subcutaneous
administration. For dose adjustment due to kidney impairment, refer to Lexicomp monographs.
Generally, anti-factor Xa monitoring is not recommended, but it can be considered for patients
with BMI ≥40 kg/m 2 who are unstable, experience unexpected thromboembolic or bleeding
complications, or require prolonged VTE treatment.
VTE: venous thromboembolism; TBW: total body weight, also known as actual body weight;
LMWH: low molecular weight heparin; FDA: Food and Drug Administration.
* Conversion: 1 mg enoxaparin is approximately equal to 100 international units enoxaparin.
¶ The 2018 American Society of Hematology (ASH) guidelines and other expert reviews suggest
against dose reduction or use of a maximum dose for VTE treatment in patients with a high BMI
citing consequences of therapeutic failure and lack of correlation between anti-factor Xa
concentrations and increased bleeding risk. [2,16]
Δ Rounding of the dose may be necessary depending on product detail. Refer to Lexicomp
monograph included with UpToDate.
◊ An empiric dose increase of approximately 30% for fixed prophylactic doses of LMWH for VTE
prophylaxis for patients with a high BMI is based on clinical experience, expert opinion, and
analysis of pharmacodynamic and clinical outcomes data. [2]
§ An optimal approach to thromboprophylaxis in bariatric surgery patients has not been

established; there is considerable variability in approach among surgeons and programs. For
additional information refer to UpToDate topics on bariatric surgery and institutional protocols.
¥ According to the US FDA approved dalteparin prescribing information, a fixed dose of 18,000
units per day is recommended for patients weighing ≥99 kg who are being treated for cancer-
associated VTE. [12] However, guidelines suggest that dalteparin dose should be based on
TBW. [2,15] Capped dalteparin dose of 18,000 units per day is not recommended.
‡ According to the Canadian approved nadroparin product monograph, a fixed dose of 17,100
units per day is recommended for patients weighing more than 100 kg. [13] However, guidelines
suggest that nadroparin dose should be based on TBW. [2,16] Capped nadroparin dose of 17,100
units per day is not recommended.
References:
1. Merli G, Spiro TE, Olsson CG, et al. Subcutaneous enoxaparin once or twice daily compared with intravenous
unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern Med 2001; 134:191.
2. Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Low-molecular-weight heparins in renal impairment and obesity:
Available evidence and clinical practice recommendations across medical and surgical settings. Ann
Pharmacother 2009; 43:1064.
3. Rondina MT, Wheeler M, Rodgers GM, et al. Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly
obese, medically-ill patients. Thromb Res 2010; 125:220.
4. Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest
2012; 141:e24S.
5. Freeman A, Horner T, Pendleton RC, Rondina MT. Prospective comparison of three enoxaparin dosing regimens to
achieve target anti-factor Xa levels in hospitalized, medically ill patients with extreme obesity. Am J Hematol 2012;
87:740.
6. Parikh S, Jakeman B, Walsh E, et al. Adjusted-dose enoxaparin for VTE prevention in the morbidly obese. J Pharm
Technol 2015; 31:282.
7. Bickford A, Majercik S, Bledsoe J, et al. Weight-based enoxaparin dosing for venous thromboembolism
prophylaxis in the obese trauma patient. Am J Surg 2013; 206:847.
8. Scholten DJ, Hoedema RM, Scholten SE. A comparison of two different prophylactic dose regimens of low
molecular weight heparin in bariatric surgery. Obes Surg 2002; 12:19.
9. Borkgren-Okonek MJ, Hart RW, Pantano JE, et al. Enoxaparin thromboprophylaxis in gastric bypass patients:
Extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis 2008; 4:625.
10. Enoxaparin sodium. United States prescribing information. Revised April 2020. Available at:
https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&type=pdf
(Accessed on November 22, 2021).
11. Al-Yaseen E, Wells PS, Anderson J, et al. The safety of dosing dalteparin based on actual body weight for the
treatment of acute venous thromboembolism in obese patients. J Thromb Haemost 2005; 3:100.
12. Dalteparin sodium injection. United States prescribing information. Revised September 2021. Available at:
https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=23527b8b-9b28-4e6d-9751-33b143975ac7&type=pdf
(Accessed on November 22, 2021).
13. Nadroparin calcium injection. Canada product monograph. Revised September 2019. Available at:
https://pdf.hres.ca/dpd_pm/00053484.PDF (Accessed on January 14, 2022).
14. Tseng EK, Kolesar E, Handa P, et al. Weight-adjusted tinzaparin for the prevention of venous thromboembolism
after bariatric surgery. J Thromb Haemost 2018; 16:2008.
15. Tinzaparin sodium injection. Canada product monograph. Revised May 2017. Available at:
https://pdf.hres.ca/dpd_pm/00040736.PDF (Accessed on November 22, 2021).
16. Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of
venous thromboembolism: Optimal management of anticoagulation therapy. Blood Adv 2018; 27:3257.
Options for parenteral venous thromboembolism (VTE) prophylaxis in

patients with cancer
Surgical patients
Hospitalized medical patients
(postoperative dosing*)
Unfractionated heparin
Unfractionated 5000 units once every 8 to 12 hours 5000 units once every 8 to 12 hours
heparin beginning 6 to 24 hours
postoperatively
Low molecular weight (LMW) heparin
Dalteparin 5000 units once daily 5000 units once daily beginning 12 to
24 hours postoperatively
Enoxaparin 40 mg once daily 40 mg once daily beginning 12 to 24

hours postoperatively
Nadroparin ¶ 3800 anti-Xa units once daily 3800 anti-Xa units once daily
beginning 12 to 24 hours
postoperatively
Tinzaparin ¶ 3500 anti-Xa units once daily 3500 anti-Xa units once daily
beginning 12 to 24 hours
postoperatively
Fondaparinux
Fondaparinux 2.5 mg once daily 2.5 mg once daily beginning 6 to 8

hours postoperatively or beginning
on the morning of the day after
surgery
These doses apply to VTE prophylaxis (not treatment) and are appropriate for patients with active
cancer. Administration is by subcutaneous injection for all of the agents listed. Dose adjustments
may be required for renal insufficiency or for obesity. For surgical patients, some surgeons will
start prophylaxis preoperatively, depending on the specific procedure, bleeding risk, and
thrombosis risk. Refer to UpToDate topics on VTE prevention in patients with cancer and VTE
treatment in patients with cancer for further information including use of parenteral as well
as oral anticoagulants.
VTE: venous thromboembolism.
* Preoperative dosing may be appropriate in selected settings as long as there is no concern

about bleeding with anticoagulation (eg, due to neuraxial anesthesia or spine surgery). Refer to
UpToDate for details of anticoagulation management in individuals undergoing neuraxial
anesthesia or procedures involving the central nervous system.
¶ Not available in the United States.
Adapted from: Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in
patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;
31:2189.
Contributor Disclosures
James D Douketis, MD, FRCPC, FACP, FCCP Consultant/Advisory Boards: AstraZeneca [Reversal of
anticoagulants for bleeding and perioperative management]; CytoSorb [Reversal of anticoagulants for
bleeding and perioperative management]; PhaseBio [Reversal of anticoagulants for bleeding and
perioperative management]; Servier [Anticoagulants for atrial fibrillation and cancer-associated
thrombosis]. Other Financial Interest: Leo Pharma [Anticoagulants for the treatment of cancer-
associated thrombosis]; Pfizer [Anticoagulants (LMWH, DOACs), management of COVID-19]. All of the
relevant financial relationships listed have been mitigated. Siraj Mithoowani, MD, MHPE, FRCPC No
relevant financial relationship(s) with ineligible companies to disclose. Jess Mandel, MD, MACP, ATSF,
FRCP No relevant financial relationship(s) with ineligible companies to disclose. David A Garcia,
MD Other Financial Interest: Abbott [Stroke prevention in atrial fibrillation]. All of the relevant financial
relationships listed have been mitigated. Geraldine Finlay, MD No relevant financial relationship(s)
with ineligible companies to disclose. Kathryn A Collins, MD, PhD, FACS No relevant financial
relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
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Prevention of Venous Thromboembolic Disease in Adult Nonorthopedic Surgical Patients - UpToDate

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Prevention of Venous Thromboembolic Disease in Adult Nonorthopedic Surgical Patients - UpToDate

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3/4/23, 20:23 Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients - UpToDate

Official reprint from UpToDate®

Prevention of venous thromboembolic disease in adult

ASSESS RISK FOR THROMBOSIS

● Procedure-related – Many procedure-related factors contribute to the risk of VTE in

● Patient-related – Patient-related VTE risk factors are discussed separately. (See

General, abdominal/pelvic, bariatric, vascular, plastic surgery — The risk categories

● General/abdominal pelvic (low to high Caprini score) – Rates of symptomatic VTE

● Plastic and reconstructive (low to high Caprini score) – In the absence of

Cardiac, thoracic, neurosurgery, major trauma — The ACCP has provided rough

● Noncardiac thoracic surgery (moderate to high Caprini score) – Several studies

● Neurosurgery (moderate to high Caprini score) – Meta-analyses report a pooled

● Moderate risk – Caprini score 3 to 4; corresponding to an EBR of about 3 percent (see

ASSESS RISK FOR MAJOR BLEEDING

● General/abdominal/pelvic surgery – 1 percent

● Bariatric surgery – <1 percent

● Plastic and reconstructive surgery – 0.5 to 1.8 percent

● Vascular surgery – 0.3 to 1.8 percent

● Cardiac surgery – 5 percent (high risk)

● Thoracic surgery – 1 percent

● Neurosurgery – Craniotomy: 1 to 1.5 percent; spinal surgery: <0.5 percent

● Major trauma – 3.4 to 4.7 percent (high risk)

underlying bleeding disorder or thrombocytopenia (eg, platelet count <50,000/microL, or

Bleeding risk categories — Following the above assessment, bleeding risk can be

● Low bleeding risk – In general, patients undergoing general, abdominal-pelvic,

Various strategies to improve the use of thromboprophylaxis methods have been

appendectomy, laparoscopic cholecystectomy) or minor thoracic surgery (eg, diagnostic

Mechanical methods of thromboprophylaxis include intermittent pneumatic compression

Graduated compression stockings — There is a paucity of high quality randomized trials

● One meta-analysis of 20 randomized trials mostly surgical and orthopedic

● In another meta-analysis of eight studies (mostly hospitalized general surgical and

● Moderate-risk surgical patients have been defined as patients undergoing general or

● High-risk surgical patients have been defined as patients undergoing general or

With low bleeding risk: Pharmacologic alone — In nonorthopedic surgical patients at

The efficacy of pharmacologic therapy in comparison with mechanical methods, and

● Pharmacologic versus no prophylaxis or mechanical methods – In general,

• LMW heparin – In a meta-analysis of eight trials of five different preparations of

● LMW heparin versus low-dose UFH – Low-dose UFH is generally considered an

● Fondaparinux versus UFH or LMW heparin – Fondaparinux is an alternative to LMW

With low bleeding risk: Combined prophylaxis — Combining pharmacologic and

● In a large meta-analysis of 34 trials, which included data on 14,931 patients (mixed

● In a meta-analysis of 25 randomized trials in mixed surgical populations, adding

● Several randomized trials of patients undergoing neurosurgical procedures reported

● In a randomized trial (APOLLO) of patients undergoing major abdominal surgery

● In a "quasi"-randomized trial (IPC SUPER) of patients undergoing major surgery and a

With high bleeding risk: Mechanical methods — For patients with contraindications to

Switching to or adding a pharmacologic agent, such as LMW heparin, should be done as

SPECIFIC SURGICAL POPULATIONS

General and abdominal/pelvic surgery

● Bariatric surgery ( table 4) (see "Bariatric surgery: Postoperative and long-term

● Colon surgery (see "Overview of colon resection", section on 'Thromboprophylaxis')

● Extremity amputation (see "Lower extremity amputation", section on

● Gynecologic surgery (see "Overview of preoperative evaluation and preparation for

Neurosurgery including neurotrauma

Anesthesia and perioperative care

● Patients undergoing neuraxial anesthesia or analgesia (see "Neuraxial

● Critically ill patients including postoperative surgical patients (see "Prevention of

● Patients with stroke (see "Prevention and treatment of venous thromboembolism in

Timing of initiation — The optimal timing for initiation of mechanical and/or

Perioperative management of anticoagulants for patients who are therapeutically

Extended pharmacologic VTE prophylaxis beyond discharge is not routinely recommended

Several meta-analyses of randomized and nonrandomized trials have demonstrated benefit

Pharmacologic dosing — Pharmacologic prophylaxis is the method of choice for surgical