ACOG

ACOG
PRACTICE
PRACTICE
BULLETIN
BULLETIN CLINICAL MANAGEMENT GUIDELINES FOR
CLINICAL O
MBSTETRICIAN
ANAGEMENT–GGYNECOLOGISTS
UIDELINES FOR
OBSTETRICIAN–GYNECOLOGISTS
NUMBER 84, AUGUST 2007
NUMBER 84, AUGUST 2007
(Replaces Practice Bulletin Number 21, October 2000)
(Replaces Practice Bulletin Number 21, October 2000)
A correction was published in January 2016 for this title. Click here to view the correction.

Prevention
Prevention of
of Deep
Deep Vein
Vein
This Practice Bulletin was Thrombosis
Thrombosis and
and
This Practice
developed
developed
by theBulletin
ACOG Com-
by the ACOG
mittee on Practice
was
Com-
Bulletins— Pulmonary Embolism
Pulmonary Embolism
mittee on Practice
Gynecology with theBulletins—
assistance
Gynecology with the assistance
of Daniel Clarke-Pearson, MD, Despite advances in prophylaxis, diagnosis, and treatment, venous thromboem-
of
andDaniel Clarke-Pearson,
Lisa N. Abaid, MD, MPH. MD, Despite advances
bolism remains in prophylaxis,
a leading cause ofdiagnosis,
disability and
and treatment, venous thromboem-
death in postoperative, hospi-
and
The Lisa N. Abaid,
information MD, MPH.
is designed to bolism
talized remains
patients a(1–3).
leading causethromboembolism
Venous of disability and death in postoperative,
most commonly occurs hospi-
in the
The
aid information
practitionersis designed
in making to talized
form ofpatients
a deep (1–3). Venous thromboembolism
vein thrombosis or pulmonary most commonly
embolism. occurs
Beyond the in the
acute
aid practitioners
decisions in making
about appropriate form of a deep vein thrombosis or pulmonary embolism. Beyond
sequelae, venous thromboembolism may result in chronic conditions, including the acute
decisions
obstetric andabout appropriate
gynecologic care. sequelae, venoussyndrome,
postthrombotic thromboembolism may result inand
venous insufficiency, chronic conditions,
pulmonary including
hypertension.
obstetric and gynecologic
These guidelines should not care.
be postthrombotic
The purpose of syndrome, venous
this bulletin is to insufficiency, and pulmonary
review the current hypertension.
literature on the use of
These guidelines
construed should
as dictating an not be
exclu- The purpose of this bulletin
thromboprophylaxis is to review
in gynecology the and
patients current literatureevidence-based
to provide on the use of
construed
sive courseasofdictating
treatment anor
exclu-
pro- thromboprophylaxis in gynecology patientsmaking.
and to provide evidence-based
recommendations to guide clinical decision
sive course
cedure. of treatment
Variations or pro-
in practice recommendations to guide clinical decision making.
cedure. Variationsbased
may be warranted in practice
on the
may
needsbeofwarranted basedpatient,
the individual on the
needs of the individual
resources, patient,
and limitations Background
resources,
unique to the and limitations
institution or type Background
Magnitude of the Problem and Epidemiology
unique to the institution or type
of practice. Magnitude of the Problem and Epidemiology
of practice. Deep vein thrombosis (DVT) and pulmonary embolism are collectively referred
Deep vein thrombosis
to as venous (DVT) and
thromboembolic pulmonary
events. embolism
The prevalence of are
DVT collectively
in patientsreferred
under-
Reaffirmed 2018 to as venous events. The prevalence
going major thromboembolic
gynecologic surgery ranges from 15% of to DVT
40% in patients under-
the absence of
going major gynecologic
thromboprophylaxis surgery
(4). The ranges of
presence from
an 15% to 40% in DVT
asymptomatic the absence
is highlyof
thromboprophylaxis
linked to the development (4). The
of a presence
clinically of an asymptomatic
significant pulmonaryDVT is highly
embolism (5).
linked to the development
Most patients who die fromofa pulmonary
a clinicallyembolism
significantsuccumb
pulmonary embolism
within (5).
30 minutes
Most
of thepatients who dielittle
event, leaving fromtime
a pulmonary embolism
for therapeutic succumb within
interventions. Thus,30clinicians
minutes
of the event,
should leaving
focus on little time
identifying forpatients
at-risk therapeutic interventions.
and instituting Thus, clinicians
consistent, effective
should focus on identifying
thromboprophylaxis to reduceat-risk patients and
the incidence instituting
of this frequent,consistent, effective
often preventable
thromboprophylaxis
cause of death. to reduce the incidence of this frequent, often preventable
causeDeep
of death.
vein thrombosis is diagnosed in two million Americans each year, and
Deep
nearly onevein
thirdthrombosis is diagnosed
of these patients in two million
will develop Americans
a pulmonary each year,
embolism, and
resulting
nearly one third of these patients will develop a pulmonary embolism, resulting
in 60,000 deaths each year (6). The incidence of a first
venous thromboembolism is 1–2 per 1,000 individuals per
year (7, 8). Pulmonary embolism is associated with a
case-fatality rate of 11–12%, although this rate is lower in
young patients and higher in patients with cancer (8, 9).
Additionally, patients undergoing bed rest are nearly nine
times more likely to develop a venous thromboembolism
(10). Hospitalization and surgery also are associated with
an increased thrombosis risk, with odds ratios of 11.1 and
5.9, respectively (10).
A recent trial of more than 2,000 patients undergoing
surgery for cancer showed a 2% rate of clinical venous
thromboembolism formation, despite the use of in-hospi-
tal prophylaxis by more than 80% of patients (11). Overall
mortality was 1.72% within 35 days of surgery, and
despite prophylaxis, 46% of the deaths were attributed to
venous thromboembolism. Given these increased odds, it
is important to identify high-risk patients because aggres-
sive thromboprophylaxis will decrease the risk of a poten-
tially fatal venous thromboembolism. Risk factors are
listed in the box.
Definitions of Low, Medium, High, and
Highest Risk
Patients should be classified preoperatively into one of
four risk categories—1) low, 2) medium, 3) high, and 4)
highest risk—to determine the appropriate thrombopro-
phylaxis regimen. The risk of venous thromboembolism
is determined based on procedure type and duration, age,
and presence of other risk factors (see box and Table 1).
Patients have different risk factors, and some prophylac-
tic regimens are neither appropriate nor effective in cer-
tain risk groups. Therefore, proper risk classification is
important in order to prescribe the best prophylactic reg-
imen. Recommendations for venous thromboembolism
prevention are described in Table 1.
Prophylaxis in Gynecologic Surgery
Rates of venous thromboembolism after gynecologic sur-
gery are similar to those reported in the general surgery
literature and average 15–40% in an untreated population
(4, 12). Graded compression stockings, intermittent pneu-
matic compression devices, low-dose unfractionated
heparin, and low molecular weight heparin (LMWH) have
each been shown to effectively reduce venous throm-
boembolism development. In two randomized trials and a
large retrospective series, the incidence of venous throm-
boembolism was reported to be 1–6.5% in a gynecologic
oncology patient population treated with one of the previ-
ously mentioned modalities (13–15). A combined regimen
of medical and mechanical prophylaxis may improve effi-
cacy, especially in the patients at highest risk for venous
2 ACOG Practice Bulletin No. 84
Venous Thromboembolism Risk Factors
Surgery
Trauma (major or lower extremity)
Immobility, paresis
Malignancy
Cancer therapy (hormonal, chemotherapy, or radio-
therapy)
Previous venous thromboembolism
Increasing age
Pregnancy and the postpartum period
Estrogen-containing oral contraception or hormone
therapy
Selective estrogen receptor modulators
Acute medical illness
Heart or respiratory failure
Inflammatory bowel disease
Myeloproliferative disorders
Paroxysmal nocturnal hemoglobinuria
Nephrotic syndrome
Obesity
Smoking
Varicose veins
Central venous catheterization
Inherited or acquired thrombophilia
Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW,
et al. Prevention of venous thromboembolism: the Seventh ACCP
Conference on Antithrombotic and Thrombolytic Therapy. Chest
2004;126(suppl):338S–400S.
thromboembolism. Although limited data exist to support
this approach in gynecology patients, studies from the gen-
eral surgery and neurosurgery literature suggest significant
benefit from a combined regimen (16, 17). Until more evi-
dence is accumulated, patients undergoing laparoscopic
surgery should be stratified by risk category (and provided
prophylaxis) similar to patients undergoing laparotomy.
Hypercoagulable States
Numerous environmental, inherited, and acquired risk
factors influence coagulability. Most inherited factors do
not result in clot formation until the onset of a precipitat-
ing event, such as pregnancy, surgery, or exogenous hor-
mone use (18). The most prevalent genetic and acquired
thrombophilias are listed in Table 2. Factor V Leiden
Table 1. Risk Classification for Venous Thromboembolism in Patients Undergoing Surgery Without Prophylaxis
Level of Risk Definition
Low Surgery lasting less than 30 minutes in patients
younger than 40 years with no additional risk factors
Moderate Surgery lasting less than 30 minutes in patients with
additional risk factors; surgery lasting less than
30 minutes in patients aged 40–60 years with no
additional risk factors; major surgery in patients
younger than 40 years with no additional risk factors
High Surgery lasting less than 30 minutes in patients older
than 60 years or with additional risk factors; major
surgery in patients older than 40 years or with
additional risk factors
Highest Major surgery in patients older than 60 years plus
prior venous thromboembolism, cancer, or molecular
hypercoagulable state
Modified from Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on
Antithrombotic and Thrombolytic Therapy. Chest 2004;126(suppl):338S–400S.
mutation and prothrombin gene mutation G20210A are
the most common mutations found in patients with a
venous thromboembolism. The presence of one of these
conditions during pregnancy or major surgery confers an
increased venous thromboembolism risk and may place
a patient into the highest risk category.
Factor V Leiden, identified in 1993 as the major cause
of activated protein C resistance, is the most common
inherited thrombophilia, and is carried by 5% of
Caucasians (19, 20). One half of patients with throm-
bophilia and 20% of patients with venous thromboem-
bolism carry this mutation. Heterozygotes have a threefold
to eightfold increased risk of venous thromboembolism;
homozygotes are more severely affected, with a 50- to 80-
fold increase in risk (21). Prothrombin G20210A mutation
is found almost exclusively in Caucasians and in 6% of
patients with venous thromboembolism. This mutation
causes an abnormally elevated prothrombin level, which
results in a venous thromboembolism rate three times
higher than baseline (22). Factor V Leiden mutation and
prothrombin mutation may be diagnosed by DNA analy-
sis; factor V Leiden mutation also can be detected in an
abnormal activated protein C resistance assay.
Antithrombin-III (AT-III), protein C, and protein S
are natural inhibitors of coagulation, and deficiencies of
these result in an increased risk of venous thromboem-
bolism. Although these deficiencies are an uncommon
cause of thrombosis, they should be considered in patients
with a strong family history of clots who test negative for
factor V Leiden and prothrombin mutation. Heterozygotes
for these three conditions have a 10-fold increased risk of
ACOG Practice Bulletin No. 84
Successful Prevention Strategies
No specific prophylaxis; early and “aggressive” mobilization
Low-dose unfractionated heparin (5,000 units every 12 hours),
low molecular weight heparin (2,500 units dalteparin or 40
mg enoxaparin daily), graduated compression stockings, or
intermittent pneumatic compression device
Low-dose unfractionated heparin (5,000 units every 8 hours),
low molecular weight heparin (5,000 units dalteparin or 40
mg enoxaparin daily), or intermittent pneumatic compression
device
Low-dose unfractionated heparin (5,000 units every 8 hours),
low molecular weight heparin (5,000 units dalteparin or 40
mg enoxaparin daily), or intermittent pneumatic compression
device/graduated compression stockings + low-dose unfrac-
tionated heparin or low molecular weight heparin
Consider continuing prophylaxis for 2–4 weeks after discharge.
venous thromboembolism, whereas most homozygotes
have severe thrombotic events in early infancy (23). All
three disorders are diagnosed using serum assays.
However, activity levels are unreliable during acute
thrombosis and while receiving anticoagulation.
Elevated homocysteine levels have been correlated
with an increase in venous thromboembolism. Hyper-
homocysteinemia can result from both genetic and
acquired conditions. Homozygous carriers of the methyl-
enetetrahydrofolate reductase variant 677T have mildly
elevated homocysteine levels and modest increases in risk
of thrombosis and arteriosclerosis (24). Acquired hyper-
homocysteinemia is associated with dietary deficiencies
in folate, vitamin B6, and vitamin B12 (25). It is currently
unclear whether homocysteine is a causative agent or
merely a marker, and whether lowering homocysteine
levels would similarly decrease venous thromboem-
bolism risk (26).
Antiphospholipid syndrome is another acquired
thrombophilia associated with arterial and venous throm-
bosis, and it is manifested by a wide variety of symptoms.
One half of patients with systemic lupus erythematosus
(SLE) test positive for antiphospholipid antibodies. Testing
includes serum assays for both lupus anticoagulant and
anticardiolipin antibodies. Lupus anticoagulant is the more
relevant test because it detects β2-glycoprotein-1 antibod-
ies, which correlate highly with thromboembolic complica-
tions and pregnancy morbidity (27). Testing should be
considered in patients with venous thromboembolism and
other risk factors such as SLE, recurrent pregnancy loss,
early or severe preeclampsia, or thrombocytopenia (28).
3
Table 2. Common Hypercoagulable States

Prevalence Can Patients Is the Test Is the Test

in the Prevalence in Be Tested Reliable Reliable in Patients
General Patients With Testing During During Acute Using Anticoagu-
Abnormality Population Thrombosis Methods Pregnancy? Thrombosis? lant therapy?
Factor V Leiden
Heterozygous 5% 20% Activated protein C No Yes Yes
resistance assay
Homozygous 0.02% — DNA analysis Yes Yes Yes
Prothrombin gene 2–3% 6% DNA analysis Yes Yes Yes
mutation G20210A
Antiphospholipid 1–2% 5% Functional assay Yes Yes Yes
antibody (eg, dilute Russell
viper venom time)
Anticardiolipin
antibodies
β2-Glycoprotein-1
antibodies
Protein C deficiency 0.2–0.5% 3% Protein C activity Yes No No
Protein S deficiency 0.03–0.13% 3.2% Protein S total Yes No No
and free antigen
Antithrombin-III 0.2–0.4% Less than 1% Antithrombin-III Yes No No
deficiency activity
Acquired hyperhomo- — 8–25% Fasting plasma Yes Unclear Yes
cysteinemia homocystine
Methylenetetrahydro- 10% 25% DNA analysis Yes Yes Yes
folate reductase 677T
carriers (homozygous)
Data from Rosendaal FR. Venous thrombosis: the role of genes, environment, and behavior. Hematology Am Soc Hematol Educ Program 2005;1–12 and Kyrle PA,
Eichinger S. Deep vein thrombosis. Lancet 2005;365:1163–74.

Prophylaxis Options citance veins of the calf. In addition to early postopera-

A variety of prophylactic methods will effectively reduce
DVT formation. Although DVT in the leg or pelvic veins
precedes most fatal pulmonary emboli, most studies have
not been sufficiently powered to show a reduction in
mortality as a result of thromboprophylaxis. However, it
seems reasonable to assume that the prevention of DVT
also will result in the reduction of pulmonary embolism.
Prophylactic methods can be divided into mechani-
cal and pharmacologic methods. Mechanical methods
reduce venous stasis and may promote endogenous fibri-
nolysis. Pharmacologic methods prevent clot formation
by effects at different points on the clotting cascade. Cost,
benefit, risk, and feasibility of each method should be
weighed in determining the appropriate prophylaxis for
an individual patient.
Graduated Compression Stockings
Most postoperative thrombi develop within 24 hours
after surgery, and these predominantly occur in the capa-
tive ambulation and elevating the foot of the bed, gradu-
ated compression stockings prevent pooling of blood in
the calves. A Cochrane review of randomized, controlled
trials reported a 50% reduction in DVT formation with
graduated compression stockings, and they were more
effective when combined with a second prophylactic
method (29). Low cost and simplicity are the main
advantages of using graduated compression stockings.
Correct fit is essential because improperly fitted stock-
ings may act as a tourniquet at the knee or mid-thigh,
causing an increase in venous stasis (30). Knee-length
stockings are as effective as thigh-length stockings and
should be preferentially used (31).
Pneumatic Compression
Intermittent pneumatic compression devices reduce stasis
by regularly compressing the calf with an inflatable pneu-
matic sleeve. When used during and after major gyneco-
logic surgery, the devices are as effective as low-dose
heparin and low molecular weight heparin in reducing

4 ACOG Practice Bulletin No. 84

DVT incidence (14, 15, 32). Most studies have included a
small number of patients and are underpowered to prove
efficacy in lowering pulmonary embolism incidence or
mortality. The benefits of using intermittent pneumatic
compression devices have been postulated to include an
increase in systemic fibrinolysis (33, 34). However, data
reported from a larger series have failed to confirm this
finding (35, 36). The devices should be used continuous-
ly until ambulation and discontinued only at the time of
hospital discharge (4). In a study of patients with gyne-
cologic malignancies undergoing surgery, the devices
were placed intraoperatively and their use was continued
for 5 days (37). Their use was associated with a threefold
reduction in venous thromboembolism.
Low-Dose Unfractionated Heparin
Low-dose unfractionated heparin is the most extensively
studied method of thromboprophylaxis. When adminis-
tered subcutaneously starting 2 hours before surgery and
continued every 8–12 hours postoperatively, numerous
controlled trials have shown low-dose unfractionated
heparin to be effective in preventing DVT (4). Two large
meta-analyses of randomized clinical trials of patients
who had undergone general surgery showed a two-thirds
reduction in fatal pulmonary embolism with the use of
low-dose unfractionated heparin every 8 hours compared
with placebo or no prophylaxis (38, 39).
Patients undergoing major gynecologic surgery for
benign indications also benefit from low-dose unfractionat-
ed heparin given in a preoperative dose and postoperatively
at 12-hour intervals (4). This approach was found to be inef-
fective in patients with gynecologic cancer (40). However,
the administration of 5,000 units of heparin beginning 2
hours preoperatively and continued every 8 hours postoper-
atively does provide effective venous thromboembolism
prophylaxis in women with gynecologic malignancies (41).
Advantages of low-dose unfractionated heparin
include well-studied efficacy and low cost. With periop-
erative low-dose unfractionated heparin use, a major con-
cern is increased intraoperative and postoperative
bleeding. Although blood loss during surgery does not
seem to be increased by the preoperative use of low-dose
unfractionated heparin administration, an increase in
postoperative bleeding has been noted, specifically in
wound hematoma formation (38, 42). Additionally, use
for more than 4 days warrants monitoring of platelet
counts because 6% of patients will experience heparin-
induced thrombocytopenia (42).
Low Molecular Weight Heparin
Advantages of low molecular weight heparin include
greater bioavailability and a once-daily dosage. These ben-
ACOG Practice Bulletin No. 84
efits result from a longer half-life, more predictable phar-
macokinetics, and equivalent efficacy when compared
with prophylactic use of low-dose unfractionated heparin
(43). Low molecular weight heparin has more antifactor
Xa and less antithrombin activity than low-dose unfrac-
tionated heparin, which may decrease medical bleeding
and wound hematoma formation. However, low molecular
weight heparin is more expensive than low-dose unfrac-
tionated heparin. Heparin-induced thrombocytopenia is
rarely observed with low molecular weight heparin, and
screening for this is not recommended (44).
Since initial reports in 1985 (45), multiple well de-
signed trials have shown low molecular weight heparin to
be a reliable method of thromboprophylaxis. Effective
venous thromboembolism prophylaxis also was shown in
patients undergoing surgery for gynecologic malignancies.
Equivalent risk reductions were seen with the use of preop-
erative and daily postoperative low molecular weight
heparin when compared with intermittent pneumatic com-
pression devices (15). A major prospective trial including
2,373 patients showed a 2% incidence of clinical venous
thromboembolism in patients undergoing general, urologic,
and gynecologic surgery for cancer who received low
molecular weight heparin prophylaxis (11). A retrospective
analysis of more than 3,500 patients showed a statistically
significant reduction in DVT and fatal pulmonary embolism
in patients receiving low molecular weight heparin prophy-
laxis compared with those who did not, although the inves-
tigators did not control for use of mechanical methods (46).
Duration of prophylaxis varies depending on risk fac-
tors. Major risk factors for the development of a clinical
venous thromboembolism include age older than 60 years,
cancer, prior venous thromboembolism, and prolonged sur-
gery or bed rest (11, 13). Of patients with cancer who devel-
op a venous thromboembolism, 40% will do so more than
21 days after surgery (11). A placebo-controlled trial of low
molecular weight heparin administered for 1 week versus
4 weeks postoperatively showed a 60% reduction in venous
thromboembolism with 4 weeks of treatment and no
increase in bleeding or thrombocytopenia (47). Patients at
the highest risk for venous thromboembolism may benefit
from prolonged low molecular weight heparin prophylaxis.
Dual Prophylaxis
The combined use of two prophylactic methods has been
examined in the general surgery literature, specifically in
patients undergoing colorectal surgery. A Cochrane
review of 19 studies showed that low-dose unfractionat-
ed heparin combined with graduated compression stock-
ings was four times more effective in preventing venous
thromboembolism than low-dose unfractionated heparin
alone (17). A randomized trial of 307 patients undergo-
5
ing neurosurgical procedures showed a significant reduc-
tion in venous thromboembolism with the use of low
molecular weight heparin and graduated compression
stockings combined over graduated compression stock-
ings alone (16). A decision analysis in high-risk gyneco-
logic oncology patients determined that combined
intermittent pneumatic compression devices and low
molecular weight heparin use is cost-effective (16).
No randomized trial data exist in the gynecology lit-
erature on the benefits of using a combination of mechan-
ical and pharmacologic prophylaxis. However, having
two of three identified risk factors that are associated
with the ineffectiveness of intermittent pneumatic com-
pression devices (age older than 40 years, cancer, prior
venous thromboembolism) places patients in the highest-
risk category for the development of venous thromboem-
bolism (13). As a result, the use of a combined approach
possesses inherent appeal because it may reduce both
hypercoagulability and venous stasis in highest-risk
patients undergoing surgery. Although data from random-
ized trials in gynecology patients are lacking, a combined
approach seems appropriate in the highest-risk patients,
and this practice is recommended by the Seventh American
College of Chest Physicians Consensus Conference (4).
Anesthesia Concerns
Use of regional anesthesia is associated with a 50%
decrease in DVT risk compared with general anesthesia
(48). However, use of spinal and epidural anesthesia in
patients receiving pharmacologic thromboprophylaxis is
a cause for concern. The risk of spinal hematoma with
low molecular weight heparin use was underscored by a
1997 public health advisory released by the U.S. Food
and Drug Administration. It described 41 patients who
developed epidural or spinal hematomas, with resultant
long-term neurologic injury, after using enoxaparin and
undergoing epidural or spinal anesthesia (49). Many of
these patients had multiple risk factors, including addi-
tional antithrombotic drug use and vascular or anatomic
spinal abnormalities. Additional risk factors for the
development of a spinal hematoma include an underlying
coagulopathy, traumatic or repeated catheter insertion,
advanced age, female sex, and catheter removal while
receiving prophylactic or therapeutic anticoagulation (4).
Although the previously mentioned risk factors are
relatively common, development of a spinal hematoma is
a rare event, and limited data exist to guide evidence-
based recommendations. The American College of Chest
Physicians suggests that spinal and epidural anesthesia be
avoided in patients with a bleeding disorder or recent use
of antithrombotic drugs, including low-dose unfractionat-
ed heparin, low molecular weight heparin, platelet inhib-
itors such as clopidogrel and ticlopidine, and vitamin K
6 ACOG Practice Bulletin No. 84
antagonists such as warfarin. Use of nonsteroidal antiin-
flammatory drugs such as aspirin and ibuprofen has not
been linked to spinal hematoma formation. Before using
neuraxial anesthesia, platelet inhibitors should be discon-
tinued for 5–14 days, low-dose unfractionated heparin or
twice daily low molecular weight heparin for 8–12 hours,
and daily low molecular weight heparin for at least 18
hours. Additionally, anticoagulant prophylaxis should be
delayed following a hemorrhagic aspirate and for 2 hours
after removal of an epidural or spinal catheter. Epidural
and spinal catheters should be removed during the nadir
of the anticoagulant effect, just before the next scheduled
dose of low-dose unfractionated heparin or low molecu-
lar weight heparin (4).
Clinical Considerations and
Recommendations
Who are candidates for perioperative venous
thromboembolism prophylaxis?
Candidates for perioperative venous thromboembolism
prophylaxis are those who have an increased risk of
postoperative venous thromboembolism. A complete
history and physical examination will identify risk fac-
tors, which may be grouped by level of risk (Table 1).
In addition, prophylaxis should be prescribed for
patients who have deficiencies of protein C, protein S, or
AT-III, and for heterozygous carriers of the factor V
Leiden or prothrombin gene mutation G20210A without
a personal history of thrombosis (15, 19, 43, 45).
Which prophylactic methods should be
considered for low-, medium-, high-, and
highest-risk patients undergoing surgery?
The recommended prophylactic options for patients in
each of the four risk categories are described in Table 1.
Low-risk patients do not require prophylaxis beyond
early and aggressive mobilization.
Most patients will require one method of thrombo-
prophylaxis, and intermittent pneumatic compression
devices have been shown to be safe, efficacious, and cost-
effective in both moderate- and high-risk patients, espe-
cially in patients at risk for bleeding complications.
Graduated compression stockings are not as extensively
studied as intermittent pneumatic compression devices
and, if used, should be limited to the knee-high length
(31). In patients with multiple risk factors, such as those
in the highest-risk category, consideration should be
given to combination prophylaxis with or without contin-
ued anticoagulant prophylaxis for up to 28 days.
 What is the optimal timing for prophylactic
therapy?
Studies of the natural history of postoperative venous
thromboembolism document that nearly 50% of occur-
rences of venous thromboembolism will begin in the first
24 hours postoperatively and 75% will begin within 72
hours of surgery (50, 51). Because venous thromboem-
bolism begins in the perioperative period, most clinical tri-
als evaluating either mechanical or pharmacologic
prophylaxis have initiated the prophylactic method before
surgery. Both graduated compression stockings and pneu-
matic compression devices should be placed before initia-
tion of surgery and continued until the patient is fully
ambulatory. Concern is commonly expressed by surgeons
that the preoperative administration of low-dose unfrac-
tionated heparin or low molecular weight heparin will
result in increased intraoperative bleeding. Meta-analysis
of many randomized trials shows that there is an increase
in intraoperative and postoperative bleeding. However,
most complications are minor wound hematomas, and
there is no increase in serious, life-threatening bleeding.
Optimal timing of the initial low molecular weight
heparin dose currently is unresolved. A prospective, ran-
domized trial including nearly 10,000 patients undergo-
ing elective general surgical, gynecologic, or urologic
procedures showed no difference in venous thromboem-
bolism formation or bleeding complications with admin-
istration of 20 mg of enoxaparin 2 hours before surgery,
compared with administration 12 hours before surgery
(52). However, the enoxaparin dose used was lower than
the 30–40-mg dose currently used for thromboprophy-
laxis, and in most studies, low molecular weight heparin
was initiated 12 hours before surgery. When initiating
low molecular weight heparin postoperatively, no data
exist in the gynecology literature to guide clinical deci-
sion making. Recent data from patients undergoing
orthopedic surgery describe a window of optimal low
molecular weight heparin initiation from 6 hours to 12
hours postoperatively. Starting low molecular weight
heparin therapy less than 6 hours after surgery is associ-
ated with increased bleeding complications, but prolong-
ing the first dose more than 12 hours after surgery may
reduce protection from venous thromboembolism (53).
Should patients discontinue use of hormonal
contraceptives or postmenopausal hormone
therapy before surgery?
Hormone therapy and oral contraceptive use have been
associated with an increased risk of venous thromboem-
bolism. In the Women’s Health Initiative, participants
using estrogen plus progestin therapy showed a doubling
ACOG Practice Bulletin No. 84
in risk of venous thrombosis from 1.7 to 3.5 events per
1,000 person-years (hazard ratio 2.1; 95% confidence
interval [CI], 1.6–2.7) (54). When using estrogen alone,
venous thromboembolism risk remains modestly elevat-
ed with a hazard ratio of 1.32 (95% CI, 0.99–1.75) (55).
Although venous thromboembolism is associated with
estrogen and progesterone use, the overall number of
events is low. No trials exist that show a reduction in
postsurgical venous thromboembolism with preoperative
discontinuation of hormone therapy; thus, this practice
should not be routinely recommended.
Prospectively collected data show a small increase in
postoperative venous thromboembolism from 0.5% to
0.96% in users of oral contraceptives (56). Despite a large
sample size of more than 17,000 women, this did not
reach statistical significance. The risk of venous throm-
boembolism with oral contraceptive use is directly relat-
ed to estrogen dose, with a decreased risk associated with
low-estrogen formulations. A case–control study includ-
ing more than 5,000 participants showed a 60% increase
in venous thromboembolism risk with the use of 50-mcg
pills, and a 40% reduction in venous thromboembolism
with the use of 20-mcg products, compared with 30–40-
mcg formulations (57). However, venous thromboem-
bolism risk remains about four times higher for oral
contraceptive users than for nonusers (58).
Prothrombotic clotting factor changes appear to per-
sist for 4–6 weeks after discontinuing oral contraceptive
use (59). Accordingly, the risks associated with stopping
oral contraception 1 month or more before major surgery
should be balanced against the risks of an unintended
pregnancy (60). In current users of oral contraceptives
having major surgical procedures, heparin prophylaxis
should be considered (60). Because of the low periopera-
tive risk of venous thromboembolism, it is currently not
considered necessary to discontinue combination oral
contraceptives before laparoscopic tubal sterilization or
other brief surgical procedures.
Which patients should be tested for clotting
abnormalities, and which tests should be
ordered?
Because of the high prevalence of the factor V Leiden
mutation in the Caucasian population, all patients who are
not Hispanic, Asian, or African American and have a his-
tory of DVT may be tested (61–69). In non-Caucasian
patients, the decision to test should be individualized.
Patients with histories of extensive or recurrent thrombosis
or family histories of thrombosis may have the factor V
Leiden mutation in combination with another congenital
or acquired disorder (21). Patients with a strong family
history of thrombosis who are negative for the factor V
7
Leiden mutation may benefit from testing for the pro-
thrombin gene mutation G20210A and deficiencies in the
natural inhibitors, including protein C, protein S, and AT-
III. Patients with a history of thrombosis, recurrent fetal
loss, early or severe preeclampsia, severe unexplained
intrauterine growth restriction, or unexplained thrombocy-
topenia may be tested for antiphospholipid antibodies.
Fasting plasma homocystine levels may be assessed, espe-
cially in women of childbearing age who have had venous
or arterial thrombosis, because elevated levels can be treat-
ed with vitamins (folic acid, vitamin B12, and vitamin B6).
The specific tests and optimal timing for testing are
described in Table 2.
What special considerations should be given
when using low molecular weight heparin in
patients undergoing regional anesthesia?
Low molecular weight heparin has a longer half-life than
heparin. Caution should be used in the timing of spinal or
epidural anesthesia in patients using low molecular weight
heparin to avoid the development of a spinal hematoma.
Activity of low molecular weight heparin is measured by
an antifactor-Xa level, which may not be widely available.
In addition, normalization of the antifactor-Xa level has
not been correlated with a reduction in spinal hematoma
risk. Given these concerns, patients receiving twice-daily
low molecular weight heparin should not receive regional
anesthesia for 8–12 hours after the last dose, and for 18
hours after a once-daily low molecular weight heparin
dose. Administration of low molecular weight heparin
should be held for 2 hours after removal of a spinal or
epidural catheter (4).
Which prophylactic methods are considered
cost-effective?
Two cost-effectiveness analyses have been performed in
patients who have undergone gynecologic surgery. All
methods were cost-effective, with pneumatic compres-
sion being the most cost-effective (70). Another study
revealed the potential cost-effectiveness of combined
prophylaxis in high-risk gynecologic cancer patients. The
authors concluded that the use of intermittent pneumatic
compression devices combined with low molecular weight
heparin was cost-effective in a high-risk group (71).
What is the appropriate treatment for patients
who are taking other medications (including
botanicals) that may alter their risks?
An estimated 38 million Americans use herbs or com-
plementary medicines each year, with more than 20% of
8 ACOG Practice Bulletin No. 84
American women reporting some use in the preceding 12
months (72). Some of these medications can interact with
commonly prescribed drugs, including anticoagulants,
underscoring the importance of taking a complete med-
ication history. A number of common herbs, in addition
to nonsteroidal antiinflammatory drugs and antiplatelet
medications such as clopidogrel, can potentiate the activ-
ity of low molecular weight heparin, unfractionated
heparin, and vitamin K antagonists and result in exces-
sive bleeding. A list of herbs and supplements with
antiplatelet or anticoagulant activity is found in the box.
Warfarin originally was derived from the sweet
clover plant, and related herbs can potentiate its action
through direct vitamin K antagonism or by intrinsic
antiplatelet activity (73). Conversely, ginseng and hyper-
icum, or St. John’s wort, can reduce warfarin concentra-
tions resulting in subtherapeutic levels. Hypericum has
been associated with breakthrough bleeding and unin-
Herbs and Supplements That May Interfere
With Anticoagulant Therapy
Chinese wolfberry
Coenzyme Q10
Cranberry juice
Curbicin
Danshen
Devil’s claw
Dong quai
Fenugreek
Garlic
Ginger
Gingko
Ginseng
Glucosamine-chondroitin
Grapefruit juice
Green tea
Melatonin
Omega-3 fish oil
Papaya extract
Quilinggao
St. John’s wort
Data from Wittkowsky AK. A systematic review and inventory of
supplement effects on warfarin and other anticoagulants. Thromb
Res 2005;117:81–6; discussion 113–5 and Basila D, Yuan CS.
Effects of dietary supplements on coagulation and platelet function.
Thromb Res 2005;117:49–53; discussion 65–7.
tended pregnancy when used with oral contraceptives.
These effects likely result from decreased levels of circu-
lating hormones due to cytochrome P-450 upregulation
(74, 75). Although many of these effects are derived from
case reports and clinical observations, avoidance of drugs
known to interact with antithrombotic medication is
advised for patients using oral or injected anticoagulants.
Summary of Conclusions
and Recommendations
The following recommendations are based on
good and consistent scientific evidence (Level A).
Alternatives for thromboprophylaxis for moderate-
risk patients include the following:
1. Graduated compression stockings placed before
initiation of surgery and continued until the
patient is fully ambulatory
2. Pneumatic compression devices placed before
the initiation of surgery and continued until the
patient is fully ambulatory
3. Unfractionated heparin (5,000 units) adminis-
tered subcutaneously 2 hours before surgery and
every 12 hours after surgery until discharge
4. Low molecular weight heparin (dalteparin 2,500
antifactor-Xa units, or enoxaparin 40 mg) admin-
istered subcutaneously, 12 hours before surgery
and once a day postoperatively until discharge
Alternatives for prophylaxis for high-risk patients
undergoing gynecologic surgery include the follow-
ing:
1. Pneumatic compression devices placed before
surgery and continued until hospital discharge
2. Unfractionated heparin (5,000 units) adminis-
tered subcutaneously 2 hours before surgery and
every 8 hours postoperatively and continued until
discharge
3. Low molecular weight heparin (dalteparin 5,000
antifactor-Xa units or enoxaparin 40 mg) admin-
istered subcutaneously, 12 hours before surgery
and once daily postoperatively until discharge
The following recommendations are based on lim-
ited scientific evidence (Level C).
Alternatives for prophylaxis for highest-risk patients
include the following:
1. Combination prophylaxis (such as the com-
bination of pneumatic compression and either low-
ACOG Practice Bulletin No. 84
dose unfractionated heparin or low molecular
weight heparin)
2. Consideration of continuing low molecular
weight heparin prophylaxis as an outpatient for
up to 28 days postoperatively
If administration of low molecular weight heparin
12 hours before surgery is impractical, initial dosing
should commence 6–12 hours postoperatively.
Low-risk patients who are undergoing gynecologic
surgery do not require specific prophylaxis other
than early ambulation.
Until more evidence is accumulated, patients under-
going laparoscopic surgery should be stratified by
risk category (and provided prophylaxis) similar to
patients undergoing laparotomy.
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In “Practice Bulletin No. 84: Prevention of deep vein
thrombosis and pulmonary embolism” from the
American College of Obstetricians and Gynecologists
(Obstet Gynecol 2007;110:429–40), there is an error
on page 6 in the first complete paragraph. In the sec-
ond sentence, the phrase “age older than 40 years” is
incorrect and should read “age older than 60 years.”
The correct sentence is as follows: “However, having
two of three identified risk factors that are associat-
ed with the ineffectiveness of intermittent pneumatic
compression devices (age older than 60 years, cancer,
prior venous thromboembolism) places patients in
the highest risk category for the development of ve-
nous thromboembolism (13).”
The MEDLINE database, the Cochrane Library, and
ACOG’s own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and November 2006. The
search was restricted to articles published in the English
language. Priority was given to articles reporting results of
original research, although review articles and commentar-
ies also were consulted. Abstracts of research presented at
symposia and scientific conferences were not considered
adequate for inclusion in this document. Guidelines pub-
lished by organizations or institutions such as the National
Institutes of Health and the American College of Obstetri-
cians and Gynecologists were reviewed, and additional
studies were located by reviewing bibliographies of identi-
fied articles. When reliable research was not available,
expert opinions from obstetrician–gynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services Task
Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
case–control analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level A—Recommendations are based on good and consis-
tent scientific evidence.
Level B—Recommendations are based on limited or incon-
sistent scientific evidence.
Level C—Recommendations are based primarily on con-
sensus and expert opinion.
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