Report from the CDC
Prevention of Venous Thromboembolism in Pregnancy:
A Review of Guidelines, 2000–2011
Ekwutosi M. Okoroh, M.D.,1Ijeoma C. Azonobi, M.D.,1Scott D. Grosse, Ph.D.,1Althea M. Grant, Ph.D.,1
Hani K. Atrash, M.D.,1and Andra H. James, M.D.2
Introduction: Pregnant women are four to five times more likely than nonpregnant women to develop venous
thromboembolism (VTE). The aim of this review is to provide an overview of guidelines in the literature on
VTE risk assessment, screening for thrombophilias, and thromboprophylaxis dissemination among pregnant
Methods: We performed a review of the published literature to identify evidence-based guidelines published
between the years 2000 and 2011. We searched for guidelines from U.S. and international organizations that
identified clinically based practice recommendations to healthcare providers on how VTE risk should be as-
sessed, thrombophilias screened, and thromboprophylaxis disseminated among pregnant women.
Results: We found nine guidelines that met our requirements for assessing VTE risk and found seven guidelines
addressing thrombophilia screening. Seven of the nine agreed that all women should undergo a risk factor
assessment for VTE either in early pregnancy or in the preconception period. Seven of the nine agreed that
pregnant women with more than one additional VTE risk factor be considered for thromboprophylaxis, and five
of the seven groups addressing thrombophilia screening agreed that selected at-risk populations should be
considered for thrombophilia screening.
Conclusions: There is some agreement between U.S. and international guidelines that women should be assessed
for VTE risk during preconception and again in pregnancy. Although there is agreement that the general
population of women should not be screened for thrombophilias, no agreement exists as to the clinical sub-
groups for which screening should be done.
embolism (VTE), a term that encompasses both deep vein
to the 2003 Morbidity and Mortality Weekly Report on preg-
nancy-related mortality, unspecified embolism was the lead-
ing cause of maternal death, at 20%.2In 2008, Clark et al.3
published an updated list of causes of maternal death; they
wereabletodistinguish PE fromamnioticfluidembolism and
found amniotic fluid embolism to be the second most com-
mon cause of death at 14%, while PE was the fifth leading
cause of death, at 9%. Published estimates of maternal mor-
in North America and Europe.1,4
regnant women are four to five times more likely
than nonpregnant women to develop venous thrombo-
Approximately 60%–80% of all VTE related to pregnancy
are DVT,5and women who experience DVT during preg-
nancy are more likely to have poorer pregnancy outcomes.6
Women who have experienced VTE during pregnancy may
develop long-term sequelae that range from edema and skin
changes to recurrent thrombosis and ulceration.7Further-
more, VTE is more difficult to diagnose in pregnant women8;
its associated signs and symptoms, such as dyspnea and pe-
ripheral edema, are nonspecific and are often seen in preg-
nancy, making diagnosis difficult. Regardless, a high index of
suspicion for VTE is prudent for all pregnant patients because
of the underlying physiologic risk, especially in situations in
which other risk factors for VTE are present.5
VTE, age >35, obesity (body mass index [BMI] >30kg/m2),
African American race, grand multiparity, and bed rest for
1Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and
Prevention, Atlanta, Georgia.
2Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
JOURNAL OF WOMEN’S HEALTH
Volume 21, Number 6, 2012
ª Mary Ann Liebert, Inc.
such conditions as preterm labor, premature rupture of
membranes (PROM), and preeclampsia.9Other risk factors
include immobility, medical conditions (e.g., lupus, diabetes,
sickle cell disease, congestive heart failure, and renal disease),
surgery (e.g., cesarean sections), trauma, and inherited
thrombophilias.8,10,11Inherited thrombophilias (e.g., factor V
Leiden and antithrombin deficiency) have been reported as
the leading cause of maternal thromboembolism.12Data from
Greer13and Rosendaal14suggested that at least 50% of cases
of VTE in pregnant women of European ancestry are associ-
ated with inherited thrombophilias.
To improve survival, avoid recurrence, prevent complica-
tions, and reduce healthcare costs, the risk of VTE in preg-
nancy must be assessed.16Clinical practice guidelines have
would benefit from thromboprophylaxis.17The purpose of
this review is to provide an overview of guidelines available
in the literature on VTE risk assessment, screening for
thrombophilias, and thromboprophylaxis dissemination for
VTE among pregnant women.
Materials and Methods
We performed a review of the published medical literature
to identify evidence-based guidelines, searching MEDLINE,
PUBMED, Embase, and the Cochrane Database of Systematic
Reviews for English-language, evidence-based articles pub-
lished between the years 2000 and 2011. We searched for
guidelines from U.S. and international organizations that of-
fered clinically based practice recommendations to healthcare
providers on how VTE risk should be assessed and how
thromboprophylaxis should be given among pregnant wo-
men. We also searched for guidelines aimed at healthcare
providers that gave clinically based recommendations on
whom to screen or test for thrombophilias both in the general
population and specifically among women before or during
The databases were searched using relevant Medical Search
Headlines (MeSH) terms and other terms as deemed pertinent.
The principal terms used were pregnancy, pregnant women,
puerperium, thrombosis, pulmonary embolism, thrombophi-
lia, postpartum thrombosis, deep vein thrombosis, blood clots,
practice guidelines, evidence-based guidelines, prevention,
heparin prophylaxis, prophylaxis, postpartum, compression
stockings, inpatient, thromboprophylaxis guidelines, primary
prevention recommendation on testing for thrombophilia,
consensus guidelines, screening for thrombophilia, counseling
for thrombophilia, consensus statement, and preconception.
We included only those articles in which the guideline
development was based on a systematic review of the litera-
ture or consensus expert opinion. We excluded review articles
but included both U.S. and international guidelines from or-
ganizations that commissioned the development of guide-
thrombophilia types and not providing recommendations for
We found nine guidelines for providers’ assessment of
VTE risk and thromboprophylaxis dissemination for preg-
nant women and seven guidelines for thrombophilia
screening in women (Table 1, supplementary material
available on line at www.liebertonline.com).The mechanism
for gathering and grading the level of evidence used in
making recommendations differed among organizations
(Appendix, supplementary material available on line at
www.liebertonline.com). For instance, whereas the British
Committee for Standards in Haematology (BCSH) and the
National Institute for Health and Clinical Excellence (NICE)
used the Grading of Recommendations Assessment, De-
velopment and Evaluation (GRADE) system to rank their
evidence, the American College of Obstetricians and Gy-
necologists (ACOG) used the U.S. Preventive Services Task
Force (USPSTF) system for grading evidence (Appendix,
After reviewing the selected guidelines, recommendations
for VTE risk assessment and thromboprophylaxis were
grouped as follows: general recommendations, cesarean sec-
tions, prior VTE, thrombophilia and no prior VTE, thrombo-
philia and prior VTE, and thrombophilia screening (Table 2,
supplementary material available on line at www.liebertonline
Eight of the nine organizations—the American College of
Chest Physicians (ACCP), the European Genetics Founda-
tion (EGF), the Queensland Maternity and Neonatal Clinical
Guidelines Program (QMNC), the Royal College of Ob-
stetricians and Gynaecologists (RCOG), NICE, the French
Society for Anesthesiology and Intensive Care (SFAR), the
Scottish Intercollegiate Guidelines Network (SIGN), and the
Society of Obstetricians and Gynaecologists of Canada
(SOGC)—agreed that all women should undergo risk factor
assessment for VTE either in early pregnancy or in the pre-
conception period. RCOG, EGF, and NICE added that the
assessment should be repeated if a pregnant woman is ad-
mitted to the hospital for any reason or develops a compli-
cation (e.g., preeclampsia). Similarly, the majority of the
organizations (ACCP, RCOG, EGF, NICE, SIGN, SFAR, and
QMNC) thought that pregnant women with more than
one additional known VTE risk factor (e.g., reduced mobility
for ‡3 days or age >35 years or obese) should be considered
for thromboprophylaxis. However, there were variations
among organizations about the risk factors to include and
how they should be used in the assessment of pregnant
With regard to how to prevent VTE after cesarean section,
there was variation in the guidelines among organizations.
ACCP recommends against the use of specific thrombopro-
phylaxis other than early mobilization after cesarean section
ACOG recommends placement of pneumatic compression
devices before cesarean delivery for all women not already
receiving thromboprophylaxis. NICE recommends offering
combined (pharmacologic and mechanical) VTE prophylaxis
to women who are pregnant and undergoing cesarean sec-
tion. For women with additional risk factors, such as obesity,
who will undergo a cesarean section, four of the nine orga-
nizations (ACCP, RCOG, SIGN, and SOGC) recommend ini-
tiation of thromboprophylaxis.
612OKOROH ET AL.
For women with a prior VTE, some of the relevant rec-
ommendations depended on whether the VTE was consid-
ered provoked, meaning associated with a risk factor other
than increased estrogen, unprovoked, or estrogen dependent.
The ACCP, ACOG, RCOG, and SIGN make this distinction
and recommend postpartum thromboprophylaxis for all
women with a prior provoked VTE, ACCP, ACOG, RCOG,
and SIGN do not recommend routine antepartum prophy-
laxis. In fact, ACCP and ACOG recommend only antepartum
surveillance for this group of women. ACOG, RCOG, and
SIGN agree that in women with unprovoked or estrogen-
dependent VTE, antepartum prophylaxis should be offered.
ACCP differs in its recommendations, offering either ante-
partum prophylaxis or surveillance for women with unpro-
voked or estrogen-dependent VTE. QMNC and SOGC do not
distinguish between provoked and unprovoked VTE. QMNC
and ACOG recommend thrombophilia screening for women
with a prior VTE. QMNC and SOGC also recommend ante-
partum and postpartum prophylaxis. QMNC includes ante-
partum surveillance and use of postpartum compression
stockings in their recommendations for women with a prior
Inherited thrombophilias and no prior VTE
The ACCP, EGF, QMNC, RCOG, SIGN, and SOGC all
recommend close surveillance antenatally and that anticoag-
ulant prophylaxis be offered after delivery. Exceptions to
these recommendations are made for women with anti-
thrombin deficiency, with more than one thrombophilic de-
EGF, QMNC, RCOG, SIGN, SOGC, and ACOG recommend
antepartum prophylaxis and postpartum anticoagulation
therapy. In contrast, ACCP recommends that women with
antithrombin deficiency receive anticoagulation prophylaxis
For women with other thrombophilias and no prior VTE,
ACCPrecommends eitherroutine surveillance orprophylaxis
during pregnancy and anticoagulation postpartum.
Thrombophilias and prior VTE or recurrent VTE
For this high-risk population of women, there was agree-
ment among the recommendations of six organizations
(ACCP, ACOG, EGF, QMNC, RCOG, and SOGC), who ad-
vise that antenatal and postpartum thromboprophylaxis
should be offered to women with a thrombophilia and a
previous or recurrent VTE.
There was agreement among most organizations that ad-
dressed thrombophilia screening not to recommend throm-
bophilia screening of the general population of pregnant
women in order to assess venous thrombosis risk—ACOG,
the College of American Pathologists (CAP), EGF, the French
Group for Haemostasis and Thrombosis (GEHT), and the
Italian Society for Haemostasis and Thrombosis (SISET).
ACOG, CAP, EGF, and SISET also agreed that nonpregnant
women with a prior VTE, whose only other risk factor was
estrogen exposure, should be tested for thrombophilias.
Other thrombophilia-related recommendations
? Women with a history of VTE who have not had a
complete evaluation of possible underlying etiologies
should be tested for both antiphospholipid antibodies
and inherited thrombophilias (ACOG).
? All patients with an inherited thrombophilia should
undergo individualized risk assessment (ACOG).
? Thrombophilia testing must be supervised by experi-
enced laboratory staff, and the clinical significance of
the results must be interpreted by an experienced cli-
nician who is aware of all relevant factors that may in-
fluence individual test results (BCSH).
? Screening for thrombophilias should be done before
pregnancy. If screening is performed during pregnancy,
the results should be interpreted with great caution
? Testing at the time of acute venous thrombosis is not
There is broad agreement among the guidelines from U.S.
and international organizations that all women should be
assessed for VTE risk during preconception and again during
pregnancy. With regard to thrombophilia screening, there is
screened but rather that screening should be done selectively;
however, no agreement exists on the exact population in
which screening should be performed.
Our review of the available guidelines and consensus
First, most are inconsistent in both the way in which the
quality of evidence is rated and the way in which the strength
of recommendations is graded. Second, the statements often
vary in their recommendations on whom to screen. Third,
most of the primary studies used to make the recommenda-
tions were conducted in populations of women of European
descent, so the risks identified are not necessarily generaliz-
able to non-European populations. Finally, some of the
guidelines have not been updated recently.
Our review of guidelines and consensus statements fol-
lows in the footsteps of Clark and Bates,18who reviewed
guidelines for antithrombotic therapy in pregnancy from
both North American and British organizations. We ex-
panded on this approach and considered organizations in
North America, Britain, and other countries, and we in-
cluded available screening guidelines for thrombophilias in
Although studies have evaluated adherence to thrombo-
prophylaxis in the general population, no study has yet ad-
dressed adherence specific to pregnant women. Furthermore,
despite the availability of these guidelines and consensus
statements, their implementation is inconsistent. The Epide-
miologic International Day for the Evaluation of Patients at
Risk for Venous Thromboembolism in the Acute Hospital
Care Setting (ENDORSE) study found 58.5% adherence to
thromboprophylaxis among surgical patients at risk and only
39.5% adherence for medical patients at risk.19Similarly, the
Thromboembolism (IMPROVE) study found that only 61% of
at-risk medical patients in the United States and in other
countries received some form of prophylaxis.20
VTE GUIDELINES IN PREGNANCY613
Based on the results of several studies, the reasons for
guideline underuse include underestimation of the risks of
VTE, failure to perform individual risk assessments, and lack
extensive, studies have shown that increasing DVT prophy-
laxis rates can decrease the rate of hospital-acquired DVT23,24
or DVT and PE.25We hope this article will raise provider
VTE in women before and during pregnancy.
on thromboprophylaxis and screening pregnant women for
VTE and thrombophilias showed agreement on some points
but not on others. There is agreement that pregnant women
should be assessed for VTE risk during pregnancy and that
the general population of pregnant women should not be
screened for thrombophilias. However, there is a lack of
overall agreement about which groups of women should be
offered thromboprophylaxis during or after pregnancy or
offered testing for thrombophilias. This review demonstrates
that partial agreement exists, and efforts should be made to
establish more areas of agreement through collaborative
We thank Barbara B. Landreth for her assistance in the lit-
erature search. We did not receive funding for writing this
review. The findings and conclusions in this article are those
of the authors and do not necessarily represent the views of
the Centers for Disease Control and Prevention.
No competing financial interests exist.
1. Liu S, Rouleau J, Joseph KS, et al. Maternal Health Study
Group of the Canadian Perinatal Surveillance System. Epi-
demiology of pregnancy-associated venous thromboembo-
lism: A population-based study in Canada. J Obstet
Gynaecol Can 2009;31:611–620.
2. Chang J, Elam-Evans LD, Berg CJ, et al. Pregnancy-related
mortality surveillance—United States, 1991–1999. MMWR
Surveill Summ 2003;52:1–8.
3. Clark SL, Belfort MA, Dildy GA, Herbst MA, Meyers JA,
Hankins GD. Maternal death in the 21st century: Causes,
prevention, and relationship to cesarean delivery. Am
J Obstet Gynecol. 2008;199:36.e1–5.
4. Lewis G, ed. The Confidential Enquiry into Maternal and
Child Health (CEMACH). Saving mothers’ Lives: Reviewing
maternal deaths to make motherhood safer—2003–2005. The
Seventh Report on Confidential Enquiries into Maternal
Deaths in the United Kingdom. London: CEMACH.
5. Marik PE. Venous thromboembolism in pregnancy. Clin
Chest Med 2010;31:731–740.
6. Duhl AJ, Paidas MJ, Ural SH, et al. Pregnancy and Throm-
bosis Working Group. Antithrombotic therapy and preg-
nancy: Consensus report
prevention and treatment of venous thromboembolism and
adverse pregnancy outcomes. Am J Obstet Gynecol 2007;197:
7. James AH, Tapson VF, Goldhaber SZ. Thrombosis during
pregnancy and the postpartum period. Am J Obstet Gynecol
8. Marik PE, Plante LA. Venous thromboembolic disease and
pregnancy. N Engl J Med 2008;359:2025–2033.
9. James AH, Jamison MG, Brancazio LR, Myers ER. Venous
thromboembolism during pregnancy and the postpartum
period: Incidence, risk factors, and mortality. Am J Obstet
10. Dresang LT, Fontaine P, Leeman L, King VJ. Venous
thromboembolism during pregnancy. Am Fam Physician
11. James AH. Pregnancy-associated thrombosis. Hematology
12. Jordaan DJ, Schoon MG, Badenhorst PN. Thrombophilia
screening in pregnancy. Obstet Gynecol Surv2005;60:394–404.
13. Greer IA. Thrombosis in pregnancy: Maternal and fetal is-
sues. Lancet 1999;353:1258–1265.
14. Rosendaal FR. Venous thrombosis: A multicausal disease.
15. Lim W, Eikelboom JW, Ginsberg JS. Inherited thrombophilia
and pregnancy associated venous thromboembolism. BMJ
16. Heit JA. The epidemiology of venous thromboembolism in
the community: Implications for prevention and manage-
ment. J Thromb Thrombolysis 2006;21:23–29.
17. Heit JA. Venous thromboembolism: Disease burden, out-
comes and risk factors. J Thromb Haemost 2005;3:1611–1617.
18. Clark P, Bates SM. North American and British guidelines
for anti-thrombotic therapy: Are we reaching consensus?
Thromb Res 2009;123(Suppl 2):S111–123.
19. Cohen AT, Tapson VF, Bergmann JF, et al., ENDORSE In-
vestigators. Venous thromboembolism risk and prophylaxis
in the acute hospital care setting (ENDORSE study): A mul-
tinational cross-sectional study. Lancet 2008;371:387–394.
20. Tapson VF, Decousus H, Pini M, et al., IMPROVE In-
vestigators. Venous thromboembolism
acutely ill hospitalized medical patients: Findings from the
International Medical Prevention Registry on Venous
Thromboembolism. Chest 2007;132:936–945.
21. Nelson Worel J. Venous thromboembolism: What is pre-
venting achievement of performance measures and consen-
sus guidelines? J Cardiovasc Nurs 2009;24(Suppl 6):S14–19.
22. Prandoni P. Prevention and treatment of venous thrombo-
embolism with low-molecular-weight heparins: Clinical
implications of the recent European guidelines. Thromb
23. Labarere J, Bosson JL, Brion JP, et al. Validation of a clinical
guideline on prevention of venous thromboembolism in
medical inpatients: A before-and-after study with systematic
ultrasound examination. J Intern Med 2004;256:338–348.
24. Bullock-Palmer RP, Weiss S, Hyman C. Innovative ap-
proaches to increase deep vein thrombosis prophylaxis rate
resulting in a decrease in hospital-acquired deep vein
thrombosis at a tertiary-care teaching hospital. J Hosp Med
25. Kucher N, Koo S, Quiroz R, et al. Electronic alerts to prevent
venous thromboembolism among hospitalized patients. N
Engl J Med 2005;352:969–977.
American College of Obstetricians and Gynecologists. Throm-
boembolism in pregnancy. Practice bulletin No. 123. Obstet
614 OKOROH ET AL.
American College of Obstetricians and Gynecologists. Inherited Download full-text
thrombophilias in pregnancy. Practice bulletin No. 124. Obstet
Baglin T, Gray E, Greaves M, et al., British Committee for
Standards in Haematology. Clinical guidelines for testing for
heritable thrombophilia. Br J Haematol 2010;149:209–220.
Bates SM, Greer IA, Pabinger I, Sofaer S, Hirsh J, American
College of Chest Physicians. Venous thromboembolism, throm-
bophilia, antithrombotic therapy, and pregnancy: American
College of Chest Physicians Evidence-Based Clinical Practice
Guidelines, 8th Edition. Chest 2008;133(Suppl 6):844S–886S.
College of American Pathologists Consensus Conference XXXVI.
Diagnostic issues in thrombophilia. Arch Pathol Lab Med
Kent N, Leduc L, Crane J, Farine D, Hodges S, Reid GJ. Pre-
vention and treatment of venous thromboembolism (VTE) in
obstetrics. SOGC Clinical Practice Guidelines. J Soc Obstet Gy-
naecol Can 2000;22:736–742.
Lussana F, Dentali F, Abbate R, et al., Italian Society for Hae-
mostasis and Thrombosis. Screening for thrombophilia and
antithrombotic prophylaxis in pregnancy: Guidelines of the
Italian Society for Haemostasis and Thrombosis. Thromb Res
National Collaborating Centre for Acute and Chronic Condi-
tions. Venous thromboembolism: Reducing the risk. Reducing
the risk of venous thromboembolism (deep vein thrombosis and
pulmonary embolism) in patients admitted to hospital. Clinical
guideline no. 92). London, UK: National Institute for Health and
Clinical Excellence, 2010.
Nicolaides AN, Fareed J, Kakkar AK, et al. Prevention and
treatment of venous thromboembolism. International Consensus
Statement (Guidelines according to scientific evidence). Int An-
Pernod G, Biron-Andreani C, Morange PE, et al. French Group
on Haemostasis and Thrombosis, French Society of Vascular
Medicine Recommendations on testing for thrombophilia in
venous thromboembolic disease: A French consensus guideline.
J Mal Vasc 2009;34:156–203.
Queensland Maternity and Neonatal Clinical Guidelines Pro-
gram. Venous thromboembolism (VTE) prophylaxis in preg-
nancy and the puerperium. Guideline No MN0910.9-V1-
Queensland Health, 2009.
Royal College of Obstetricians and Gynaecologists. Reducing the
risk of thrombosis and embolism during pregnancy and the
puerperium. Green-top guideline No. 37. London, UK: Royal
College of Obstetricians and Gynaecologists. 2009.
Samama CM, Albaladejo P, Benhamou D, et al. Venous throm-
boembolism prevention in surgery and obstetrics: Clinical
practice guidelines: French Society for Anesthesiology and In-
tensive Care. Eur J Anesthesiol 2006:23:95–116.
Scottish Intercollegiate Guidelines Network. Prevention and
management of venous thromboembolism. A national clinical
guideline. SIGN publication no. 122. Edinburgh, Scotland:
Scottish Intercollegiate Guidelines Network, 2010.
Address correspondence to:
Ekwutosi M. Okoroh, M.D., M.P.H.
Divison of Blood Disorders
National Center for Birth Defects and Developmental Disabilities
1600 Clifton Road, Mailstop E64
Atlanta, GA 30333
VTE GUIDELINES IN PREGNANCY615