718 VOL. 118, NO.

3, SEPTEMBER 2011 OBSTETRICS & GYNECOLOGY

PRACTI CE
BULLETI N
the american college of obstetricians and gynecologists
womens health care physicians
Background
Deepveinthrombosis(DVT)andpulmonaryembolism
(PE) are collectively referred to as venous thromboem-
bolic events. Approximately 7580% of cases of preg-
nancy-associated venous thromboembolism are caused
by DVT, and 2025% of cases are caused by PE (3, 7,
13).Onehalfoftheseeventsoccurduringpregnancyand
onehalfoccurduringthepostpartumperiod(38).
Pregnancy-Associated Changes and
Venous Thromboembolism
Pregnancy is associated with physiologic and anatomic
changes that increase the risk of thromboembolism,
including hypercoagulability, increased venous stasis,
decreased venous outflow (14, 15), compression of the
inferior vena cava and pelvic veins by the enlarging
uterus(16),anddecreasedmobility(1720).Pregnancy
altersthelevelsofcoagulationfactorsnormallyrespon-
sibleforhemostasis.Theoveralleffectofthesechanges
isanincreasedthrombogenicstate(seeTable1).When
DVT occurs during pregnancy, it is more likely to
involvetheleftlowerextremity(2123).
Risk Factors
Theriskofvenousthromboembolismmaybehigherin
the third trimester compared with the first and second
trimesters (2), but the increased risk of venous throm-
boembolismispresentfromthefirsttrimester(22,23),
oftenbeforemanyoftheanatomicchangesofpregnancy
occur. The risk of venous thromboembolism is higher
duringthepostpartumperiodthanitisduringpregnancy,
especiallyduringthefirstweekpostpartum(1).
Themostimportantindividualriskfactorforvenous
thromboembolisminpregnancyisapersonalhistoryof
thrombosis.Theriskofrecurrentvenousthromboembo-
Thromboembolism in Pregnancy
Pregnant women have a fourfold to fivefold increased risk of thromboembolism compared with nonpregnant women
(1, 2). Approximately 80% of thromboembolic events in pregnancy are venous (3), with a prevalence of 0.52.0 per
1,000 pregnant women (49). Venous thromboembolism, including pulmonary embolism, accounts for 1.1 deaths per
100,000 deliveries (3), or 9 % of all maternal deaths in the United States (10). In the developing world, the leading
cause of maternal death is hemorrhage (11); however, in developed nations, where hemorrhage is more often success-
fully treated and prevented, thromboembolic disease is one of the leading causes of death (12).
The prevalence and severity of this condition during pregnancy and the peripartum period warrant special consider-
ation of management and therapy. Such therapy includes the treatment of acute thrombotic events and prophylaxis for
those at increased risk of thrombotic events. The purpose of this document is to provide information regarding the risk
factors, diagnosis, management, and prevention of thromboembolism, particularly venous thromboembolism in pregnancy.
Number 123, September 2011 Replaces Practice Bulletin Number 19, August 2000
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIANGYNECOLOGISTS
Committee on Practice BulletinsObstetrics.ThisPracticeBulletinwasdevelopedbytheCommitteeonPracticeBulletinsObstetricswiththeassis-
tanceofAndraJames,MD.Theinformationisdesignedtoaidpractitionersinmakingdecisionsaboutappropriateobstetricandgynecologiccare.These
guidelinesshouldnotbeconstruedasdictatinganexclusivecourseoftreatmentorprocedure.Variationsinpracticemaybewarrantedbasedontheneeds
oftheindividualpatient,resources,andlimitationsuniquetotheinstitutionortypeofpractice.
VOL. 118, NO. 3, SEPTEMBER 2011 Practice BulletinThromboembolism in Pregnancy 719
lismduringpregnancyisincreasedthreefoldtofourfold
(relative risk, 3.5; 95% confidence interval, 1.67.8),
and 1525% of all cases of venous thromboembolism
in pregnancy are recurrent events (24). The next most
important individual risk factor for venous thrombo-
embolism in pregnancy is the presence of a throm-
bophilia (3, 23). Thrombophilia is present in 2050%
of women who experience venous thromboembolism
duringpregnancyandthepostpartumperiod(25).Both
acquired and inherited thrombophilias increase the risk
ofvenousthromboembolism(26).
Besides a personal history of thrombosis, other
risk factors for the development of pregnancy-associ-
ated venous thromboembolism include the physiologic
changes that accompany pregnancy and childbirth,
medical factors (such as obesity, hemoglobinopathies,
hypertension, and smoking), and pregnancy complica-
tions(includingoperativedelivery)(3,68,17,27,28).
Anticoagulation Medications in
Pregnancy
Theuseofanticoagulationtherapyinwomenduringpreg-
nancywarrantsspecialconsiderationforbothmotherand
fetus. Most women who require anticoagulation therapy
beforeconceptionwillneedtocontinuethistherapydur-
ingpregnancyandthepostpartumperiod.Commonanti-
coagulation medications include unfractionated heparin,
low molecular weight heparin (LMWH), and warfarin.
The preferred anticoagulants in pregnancy are heparin
compounds.
Heparin Compounds
Neither unfractionated heparin nor LMWH crosses the
placenta (29, 30) and both are considered safe in preg-
nancy (31). Unique considerations regarding the use of
anticoagulationtherapyinpregnancyincludea4050%
increase in maternal blood volume; an increase in glo-
merularfiltration,whichresultsinincreasedrenalexcre-
tion of heparin compounds; and an increase in protein
bindingofheparin(32).Duringpregnancy,bothunfrac-
tionatedheparinandLMWHhaveshorterhalf-livesand
lowerpeakplasmaconcentrations,usuallynecessitating
higher doses and more frequent administration in order
tomaintaineffectiveconcentrations(3339).
There are few comparative studies of LMWH use
in pregnancy, but in nonpregnant patients, LMWH has
beenassociatedwithfeweradverseeffectsthanunfrac-
tionated heparin (40). Potential advantages of LMWH
include fewer bleeding episodes, a more predictable
therapeutic response, a lower risk of heparin-induced
thrombocytopenia,alongerhalf-life,andlessbonemin-
eraldensityloss(31,41,42).
Importantly,neitherLMWHnorunfractionatedhep-
arin is associated with significant bone loss when used
inprophylacticdosesduringpregnancy(4345).Unfrac-
tionated heparin, which is associated with increased
bruising at the injection sites, also has been associated
with other skin reactions and serious allergic reactions
(46). Moreover, unfractionated heparin is dispensed in
multiple-dose vials, which are potentially vulnerable to
contamination (47). Besides its greater cost, a relative
disadvantageofLMWHatthetimeofdeliveryisitslon-
gerhalf-life,whichisanimportantconsiderationforboth
neuraxialanesthesiaandperipartumbleedingrisk.
Warfarin
Warfarin,acommonagentforlong-termanticoagulation
therapy outside of pregnancy, has been associated with
potentially harmful fetal effects, especially with first-
trimester exposure (4854). Warfarin embryopathy has
been linked with exposure at 612 weeks of gestation,
highlighting the importance of early pregnancy care in
suchpatients(55).Therefore,formostwomenreceiving
prolonged anticoagulation therapy who become preg-
nant, it is recommended that unfractionated heparin or
LMWHbeusedinplaceofwarfarin.
Althoughrarelyprescribedinpregnancy,warfarinis
stillconsideredinpregnancyforwomenwithmechani-
calheartvalvesbecauseoftheirhighriskofthrombosis
Table 1. Changes in the Normal Functioning of the
Coagulation System During Pregnancy
Coagulant Factors Change in Pregnancy
Procoagulants
Fibrinogen Increased
FactorVII Increased
FactorVIII Increased
FactorX Increased
VonWillebrandfactor Increased
Plasminogenactivatorinhibitor-1 Increased
Plasminogenactivatorinhibitor-2 Increased
FactorII Nochange
FactorV Nochange
FactorIX Nochange
Anticoagulants
FreeProteinS Decreased
ProteinC Nochange
AntithrombinIII Nochange
Data from Bremme KA. Haemostatic changes in pregnancy. Best Practice &
ResearchClinicalHaematology.2003;16:15368andMedcalfRL,StasinopoulosSJ.
Theundecidedserpin:theinsandoutsofplasminogenactivatorinhibitortype2.
FEBSJ2005;272:485867.
720 Practice Bulletin Thromboembolism in Pregnancy OBSTETRICS & GYNECOLOGY
even with heparin or LMWH anticoagulation therapy
(56). The management of such women requires a multi-
disciplinary care approach, and the decision regarding
optimal anticoagulation therapy merits a detailed discus-
sionwiththepatientandherhealthcareprovidersregard-
ingtherisksandbenefitsofthevarioustreatmentoptions.
Clinical Considerations and
Recommendations
Whatistheappropriateevaluationofwomen
withapriorvenousthromboembolism?
Womenwithahistoryofthrombosiswhohavenothad
a complete evaluation of possible underlying etiologies
should be tested for both antiphospholipid antibodies
(57) and for inherited thrombophilias (58). The results
of thrombophilia testing in women with a prior venous
thromboembolism may alter the need for treatment or
theintensityoftreatmentfromaprophylactictoathera-
peutic dose (also known as adjusted-dose or weight-
baseddose)ofLMWHorunfractionatedheparin(59).
Howisavenousthromboembolism
diagnosedinpregnancy?
Deep Vein Thrombosis
ThetwomostcommoninitialsymptomsofDVT,present
in more than 80% of women with pregnancy-associated
DVT, are pain and swelling in an extremity (23). A
difference in calf circumference of 2 cm or more is par-
ticularly suggestive of DVT in a lower extremity (60).
When signs or symptoms suggest new-onset DVT, the
recommendedinitialdiagnostictestiscompressionultra-
sonographyoftheproximalveins(40).Whenresultsare
negative and iliac vein thrombosis is not suspected, rou-
tinesurveillancemaybeareasonableoption(seeFig.1).
When results are negative or equivocal and iliac vein
thrombosisissuspected,additionalconfirmatoryimaging
with magnetic resonance imaging is recommended (61).
Alternatively, depending on the clinical circumstances,
empiric anticoagulation may be a reasonable option (see
Fig.1).AlthoughmeasurementofD-dimerlevelsisause-
fulscreeningtooltoexcludevenousthromboembolismin
the nonpregnant population, pregnancy is accompanied
byaprogressiveincreaseinD-dimerlevels,evenahigh
D-dimerleveldoesnotpredictvenousthromboembolism
inpregnancy(6264).
Pulmonary Embolism
The diagnosis of new-onset PE is similar to that in
the nonpregnant individual. Both ventilationperfusion
scanning and computed tomographic (CT) angiogra-
phy are associated with relatively low radiation expo-
sure for the fetus (65). The concerns about maternal
breastradiationexposurewithCTangiographymustbe
weighedagainstthepotentialconsequencesofwithhold-
ing appropriate imaging and failing to make a proper
diagnosis. A recent study concluded that a chest X-ray
couldbeusedasadiscriminatortoreducethelikelihood
ofnondiagnosticventilationperfusionscanningandCT
angiographyinthissetting(66).
Whoarecandidatesforanticoagulation
therapyduringpregnancy?
Therapeutic anticoagulation is recommended for all
women with acute venous thromboembolism during
pregnancy. Other candidates for either prophylactic or
therapeutic anticoagulation during pregnancy include
women with a history of thrombosis or those who are
at significant risk of venous thromboembolism during
pregnancyorthepostpartumperiod,suchasthosewith
Suspect lower
extremity deep vein thrombosis
Compression
ultrasonography of
lower extremity or
extremities
Results
Negative or
equivocal and
suspect iliac vessel
process
Additional
imaging studies
Presumptive
anticoagulation
therapy
Results
Routine
surveillance
Treat
Fig. 1.Diagnosisofdeepveinthrombosisduringpregnancy.
FigureprovidedcourtesyofLeoR.Brancazio,MD.
Negative and
do not suspect
iliac vessel
process
Positive
Positive
Negative
VOL. 118, NO. 3, SEPTEMBER 2011 Practice BulletinThromboembolism in Pregnancy 721
high-risk acquired or inherited thrombophilias (see
Table2).
Despite the increased risk of venous thromboem-
bolism during pregnancy and the postpartum period,
routine anticoagulation therapy for all pregnant women
is not warranted (67, 68). Bleeding complications can
arise from administration of unfractionated heparin or
LMWH, and this complication should be considered
beforeinitiatinganticoagulationtherapy(31,41,69,70).
Howshouldanticoagulationtherapybe
administered?
There are no large trials regarding the optimal dose of
anticoagulants in pregnancy, and recommendations for
their use are based on case series and expert opinion.
Therapeuticanticoagulationisrecommendedforwomen
with acute thromboembolism during the current preg-
nancyorthoseathighriskofthrombosis,suchaswomen
withmechanicalheartvalves(40).Thedecisionregard-
ing intensity of treatment may be shaped by other risk
factorssuchascesareandelivery,prolongedimmobility,
obesity,andfamilyhistoryofthrombophiliasorvenous
thromboembolism (see Table 3). For women with a
history of idiopathic thrombosis or those with transient
risk factors who are not taking anticoagulants as a life-
long treatment and have either no thrombophilia or a
low-riskthrombophilia,expertsrecommendantepartum
prophylacticanticoagulationorantepartumsurveillance
Table 2. Recommended Thromboprophylaxis for Pregnancies Complicated by Inherited Thrombophilias*
Clinical Scenario Antepartum Management Postpartum Management
Low-riskthrombophilia

withoutpreviousVTE Surveillancewithoutanticoagulation Surveillancewithoutanticoagulationtherapy

therapyorprophylacticLMWHorUFH orpostpartumanticoagulationtherapyif
thepatienthasadditionalrisksfactors

Low-riskthrombophilia

withasingleprevious Prophylacticorintermediate-doseLMWH/UFH Postpartumanticoagulationtherapyor

episodeofVTENotreceivinglong-term orsurveillancewithoutanticoagulation intermediate-doseLMWH/UFH
anticoagulationtherapy therapy
High-riskthrombophilia

withoutpreviousVTE ProphylacticLMWHorUFH Postpartumanticoagulationtherapy

High-riskthrombophilia

withasingleprevious Prophylactic,intermediate-dose,oradjusted- Postpartumanticoagulationtherapyor

episodeofVTENotreceivinglong-term doseLMWH/UFHregimen intermediateoradjusted-doseLMWH/UFHfor
anticoagulationtherapy 6weeks(therapylevelshouldbeatleastas
highasantepartumtreatment)
Nothrombophiliawithprevioussingle Surveillancewithoutanticoagulation Postpartumanticoagulationtherapy
II
episodeofVTEassociatedwithtransient therapy
riskfactorthatisnolongerpresent
Excludespregnancy-orestrogen-related
riskfactor
Nothrombophiliawithprevioussingle Prophylactic-doseLMWHorUFH
II
Postpartumanticoagulationtherapy
episodeofVTEassociatedwithtransientrisk
factorthatwaspregnancy-orestrogen-related
Nothrombophiliawithprevioussingleepisode Prophylactic-doseLMWHorUFH
II
Postpartumanticoagulationtherapy
ofVTEwithoutanassociatedriskfactor
(idiopathic)Notreceivinglong-term
anticoagulationtherapy
Thrombophiliaornothrombophiliawithtwo Prophylacticortherapeutic-doseLMWH Postpartumanticoagulationtherapy
ormoreepisodesofVTENotreceivinglong- or or
termanticoagulationtherapy Prophylacticortherapeutic-doseUFH Therapeutic-doseLMWH/UFHfor6weeks
Thrombophiliaornothrombophiliawithtwo Therapeutic-doseLMWHorUFH Resumptionoflong-termanticoagulation
ormoreepisodesofVTEReceivinglong-term therapy
anticoagulationtherapy
Abbreviations:LMWH,lowmolecularweightheparin;UFH,unfractionatedheparin;VTE,venousthromboembolism.
*Postpartum treatment levels should be greater or equal to antepartum treatment. Treatment of acute VTE and management of antiphospholipid syndrome are
addressedinotherPracticeBulletins.

Low-riskthrombophilia:factorVLeidenheterozygous;prothrombinG20210Aheterozygous;proteinCorproteinSdeficiency.

First-degreerelativewithahistoryofathromboticepisodebeforeage50years,orothermajorthromboticriskfactors(eg,obesity,prolongedimmobility).

High-risk thrombophilia: antithrombin deficiency; double heterozygous for prothrombin G20210A mutation and factor V Leiden; factor V Leiden homozygous or
prothrombinG20210Amutationhomozygous.
||
Surveillancewithoutanticoagulationissupportedasanalternativeapproachbysomeexperts.
722 Practice Bulletin Thromboembolism in Pregnancy OBSTETRICS & GYNECOLOGY
66%ofwhomreceivedoncedailyLMWH(71).Another
studycomparingoncedailytinzaparinversustwicedaily
tinzaparinforthetreatmentofvenousthromboembolism
inpregnancyfoundthatahigher-than-recommendeddos-
agewasrequiredtomaintainanti-Xaactivityinthetarget
rangeinwomenwhotooktinzaparinonlyonceaday(36).
Another retrospective study of the once-a-day tinzaparin
regimen found two unusual thrombotic complications
among37pregnancies(72).Anyadjustmentforobesityis
incorporated into therapeutic-dose regimens. There is no
evidenced-basedprotocolforadjustingprophylacticdoses
inwomenwhoareobese,thusadjustmentscanbemade
onacase-by-casebasis.
Whichanticoagulantsshouldbeusedin
casesofheparinallergy?
In cases of severe cutaneous allergies or heparin-
induced thrombocytopenia in pregnancy, fondaparinux
(a synthetic pentasaccharide) may be the preferred anti-
coagulantbecausedanaparoid,anLMWHwithminimal
cross-reactivityinheparin-sensitivepatients,iscurrently
unavailableintheUnitedStates(73).However,thereare
insufficientdatatojustifytheroutineuseoffondaparinux
as an alternative to heparins for prophylaxis of venous
thromboembolisminpregnancy.Althougharecentretro-
spectivestudycomparingfondaparinuxwithenoxaparin
administeredbetweenday6oftheconceptioncycleand
continueduntil12weeksofgestationfoundnountoward
effectsoffondaparinuxonmotherorinfant(74),antico-
agulantactivityhasbeendetectedinumbilicalcordblood
ofexposedfetuses(75).
Howisnewlydiagnosedvenousthromboem-
bolisminpregnancymanaged?
Management of newly diagnosed venous thromboem-
bolism requires therapeutic anticoagulation with either
unfractionated heparin or LMWH (Table 3). Hospital-
ization for the initiation of anticoagulation therapy
may be indicated in cases of hemodynamic instabil-
ity, large clots, or maternal comorbidities. Intravenous
unfractionated heparin can be considered in the initial
treatment of PE and in situations in which delivery,
surgery,orthrombolysis(indicatedforlife-threateningor
limb-threateningthromboembolism)maybenecessary.
When patients appear to be hemodynamically stable,
therapeuticLMWHcanbesubstitutedinanticipationof
dischargefromthehospital.
Howshouldanticoagulationtherapybe
monitoredduringpregnancy?
Dataareunclearregardingoptimalsurveillanceofanti-
coagulation therapy during pregnancy. When used in
and postpartum prophylaxis (40). Patients with an inci-
dentally discovered low-risk thrombophilia who have
not had a prior venous thromboembolism can be man-
agedantepartumwitheithersurveillanceorprophylactic
LMWHorunfractionatedheparin,andinthepostpartum
period with either LMWH and unfractionated heparin
prophylaxis or with surveillance if the patient has no
additionalriskfactorsforDVT.
Basedonthepharmacokineticsoftheheparinagents
inpregnancy,therapeuticLMWHshouldbeadministered
onceortwicedailyandunfractionatedheparin,every12
hours (Table 3) (3438). A retrospective study of once
daily versus twice daily doses of various heparins for
venous thromboembolism in pregnancy found no cases
of recurrent venous thromboembolism in 126 women,
Table 3. Anticoagulation Regimens
Management Type Dosage
ProphylacticLMWH* Enoxaparin,40mgSConcedaily
Dalteparin,5,000unitsSConcedaily
Tinzaparin,4,500unitsSConcedaily
TherapeuticLMWH

Enoxaparin,1mg/kgevery12hours
(Alsoreferredtoas Dalteparin,200units/kgoncedaily
weight-adjusted, Tinzaparin,175units/kgoncedaily
full-treatmentdose) Dalteparin,100units/kgevery12hours
MinidoseprophylacticUFH UFH,5,000unitsSCevery12hours
ProphylacticUFH UFH,5,00010,000unitsSCevery
12hours
UFH,5,0007,500unitsSCevery
12hoursinfirsttrimester
UFH,7,50010,000unitsSCevery
12hoursinthesecondtrimester
UFH,10,000unitsSCevery12hours
inthethirdtrimester,unlesstheaPTT
iselevated
TherapeuticUFH UFH,10,000unitsormoreSCevery
(Alsoreferredtoas 12hoursindosesadjustedtotarget
weight-adjusted, aPTTinthetherapeuticrange(1.52.5,
full-treatmentdose) 6hoursafterinjection)
Postpartumanticoagulation ProphylacticLMWH/UFHfor46weeks
or
VitaminKantagonistsfor46weeks
withatargetINRof2.03.0,withinitial
UFHorLMWHtherapyoverlapuntilthe
INRis2.0ormorefor2days
Surveillance

Abbreviations:LMWH,lowmolecularweightheparin;SC,subcutaneously;UFH,
unfractionatedheparin;aPTT,activatedpartialthromboplastintime;INR,inter-
nationalnormalizedratio.
*Althoughatextremesofbodyweight,modificationofdosemayberequired.

Maytargetananti-Xalevelinthetherapeuticrangeof0.61.0units/mLfortwice
dailyregimen;slightlyhigherdosesmaybeneededforaonce-dailyregimen.

Clinical vigilance and appropriate objective investigation of women with symp-

tomssuspiciousofdeepveinthrombosisorpulmonaryembolismmaybeneeded.
VOL. 118, NO. 3, SEPTEMBER 2011 Practice BulletinThromboembolism in Pregnancy 723
therapeuticdosestotreatorpreventvenousthromboem-
bolism,itisnotclearwhetherthedoseofLMWHneeds
tobeadjusted.Onthebasisofsmallstudiesdemonstrat-
ingtheneedforincreasedLMWHtomaintainantifactor
Xalevelsbetween0.6units/mLand1.0units/mL,some
advocate periodic measurement of antifactor Xa levels
46 hours after injection, but other studies have shown
that few women actually require increased doses when
weight-baseddosesareused(40).Patientsconvertedtoa
subcutaneoustherapeuticdoseofunfractionatedheparin
inthelastmonthofpregnancyshouldhaveanactivated
partial thromboplastin time (aPTT) checked (aPTT of
1.52.5,6hoursafterinjection)andtheirdoseofheparin
adjustedtomaintaintheaPTTinthetherapeuticrange.
Patients receiving prophylactic anticoagulation do
not require monitoring, but measurement of antifactor
Xa levels or aPTT may be warranted in cases in which
prophylaxislevelsoutsideoftherecommendedrangeare
clinically suspected (39). In one study, approximately
40% of women taking prophylactic LMWH had levels
outsideoftheprophylacticrange(39).
Guidelines recommend obtaining platelet counts
wheninitiatingtherapeuticunfractionatedheparintherapy
inordertomonitorforheparin-inducedthrombocytopenia
(76).Thedataarelessclearaboutmeasuringplateletlev-
els when initiating LMWH, but case reports of heparin-
inducedthrombocytopeniahavebeendescribed(77).
Howisanticoagulationtherapymanagedat
thetimeofdelivery?
Women receiving either therapeutic or prophylactic
anticoagulationtherapymaybeconvertedfromLMWH
totheshorterhalf-lifeunfractionatedheparininthelast
monthofpregnancyorsoonerifdeliveryappearsimmi-
nent. An alternative option may be to stop therapeutic
anticoagulationandinducelaborwithin24hours,ifclin-
icallyappropriate.Thepurposeofconversiontounfrac-
tionatedheparinhaslesstodowithanyriskofmaternal
bleedingatthetimeofdelivery,butrathertheriskofan
epidural or spinal hematoma with regional anesthesia.
TheAmericanSocietyofRegionalAnesthesiaandPain
Medicine guidelines recommend withholding neuraxial
blockade for 1012 hours after the last prophylactic
dose of LMWH or 24 hours after the last therapeutic
dose of LMWH (78). These guidelines support the use
of neuraxial anesthesia in patients receiving dosages of
5,000unitsofunfractionatedheparintwicedaily,butthe
safety in patients receiving 10,000 units twice daily or
more is unknown. In such cases, the American Society
ofRegionalAnesthesiaandPainMedicinerecommends
assessmentonanindividualbasis(78).Ifawomangoes
intolaborwhiletakingunfractionatedheparin,clearance
canbeverifiedbyanaPTT.Reversalofheparinisrarely
requiredandisnotindicatedwithaprophylacticdoseof
heparin. For women in whom anticoagulation therapy
has temporarily been discontinued, pneumatic compres-
sionsdevicesarerecommended.
Shouldpatientsundergoingcesareandelivery
receiveDVTprophylaxis?
Cesarean delivery approximately doubles the risk of
venousthromboembolism(6),butintheotherwisenormal
patient, this risk is still low (approximately 1 per 1,000
patients) (79). Given this increased risk, and based on
extrapolationfromperioperativedata,placementofpneu-
matic compression devices before cesarean delivery is
recommendedforallwomennotalreadyreceivingthrom-
boprophylaxis. Studies of routine thromboprophylaxis
forcesareandeliveryhavebeensmallandnotadequately
powered to assess a decrease in the risk of DVT or PE
with anticoagulation therapy (8082). One published
decision analysis concluded that if thromboprophylaxis
was elected, pneumatic compression devices were pre-
ferred to unfractionated heparin because of the risk of
bleeding complications and heparin-induced thrombocy-
topenia (83). Another decision analysis concluded that
pneumaticcompressiondeviceswerecosteffectiveifthe
incidence of postcesarean venous thromboembolism in
thepopulationwasatleast6.8per1,000patients(84).
Forpatientsundergoingcesareandeliverywithaddi-
tional risk factors for thromboembolism, individual risk
assessment may require thromboprophylaxis with both
pneumaticcompressiondevicesandunfractionatedhepa-
rin or LMWH (40). However, cesarean delivery in the
emergency setting should not be delayed because of
the timing necessary to implement thromboprophylaxis.
Mostpatientsreceivingthromboprophylaxisduringpreg-
nancywillbenefitfrompostpartumthromboprophylaxis,
butthedoseandroutewillvarybyindication(85).
Additional measures should be considered for cer-
tain women at particularly high risk of thrombosis at
the time of delivery. Women who have antithrombin
deficiency may be candidates for antithrombin concen-
tratesperipartum.WomenwhohavehadDVTinthe24
weeks before delivery may be candidates for placement
of a retrievable vena caval filter, with removal postpar-
tum (86, 87). Other women who may be candidates for
vena caval filter placement during pregnancy include
womenwithrecurrentvenousthromboembolismdespite
therapeuticanticoagulation(87).
Whenistheoptimaltimetoresumeanti-
coagulationtherapypostpartum?
The optimal time to restart anticoagulation therapy
postpartum is unclear. A reasonable approach to mini-
724 Practice Bulletin Thromboembolism in Pregnancy OBSTETRICS & GYNECOLOGY
mize bleeding complications is to restart unfractionated
heparinorLMWHnosoonerthan46hoursaftervagi-
nal delivery or 612 hours after cesarean delivery. One
study of 95 women treated with peripartum enoxaparin
comparedwith303controlsfoundnosignificantincrease
intherateofseverepostpartumhemorrhagewhenenoxa-
parin was restarted between 5 hours and 24 hours after
a vaginal delivery and between 12 hours and 36 hours
afteracesareandelivery(88).Currentrecommendations
by American Society of Regional Anesthesia and Pain
MedicineareforresumptionofprophylacticLMWHno
soonerthan2hoursafterepiduralremoval(78).Because
theoptimalintervalforresumptionoftherapeuticantico-
agulationafterepiduralremovalisunclear,12hoursmay
be a reasonable approach. When reinstitution of antico-
agulationtherapyisplannedpostpartum,pneumaticcom-
pressiondevicesshouldbeleftinplaceuntilthepatientis
ambulatoryanduntilanticoagulationtherapyisrestarted.
Womenwhorequiremorethan6weeksoftherapeu-
tic anticoagulation may be bridged to warfarin (8991).
Bridgingtowarfarinrequireswomentotaketwoantico-
agulantssimultaneously.Forwomenwhorequireonly6
weeksofanticoagulationtherapypostpartum,theutility
ofwarfarinislimitedbecauseitfrequentlyrequires12
weeks of administration before a therapeutic range is
attained. Consequently, many patients opt to continue
LMWHforthe6-weekperiod.Womenwhohaveexperi-
encedvenousthromboembolismduringthecurrentpreg-
nancy,especiallythoseinthethirdtrimester,willlikely
needtocontinuetakingwarfarinformorethan6weeks
afterdelivery;someexpertsrecommendtakingwarfarin
foratleast36monthsdependingonthecircumstances
(92).Becausewarfarin,LMWH,andunfractionatedhep-
arindonotaccumulateinbreastmilkanddonotinduce
ananticoagulanteffectintheinfant,theseanticoagulants
arecompatiblewithbreastfeeding(89,93,94).
Whatpostpartumhormonalcontraceptive
optionsareappropriateforwomenwith
thrombophilias?
The risk of venous thromboembolism among women
taking estrogen-containing oral contraceptives increases
35-fold to 99-fold and increases 16-fold among women
heterozygous for factor V Leiden and prothrombin
G20210A mutations (95). The annual risk of venous
thromboembolism is 5.7 per 10,000 among factor V
Leiden carriers but increases to 28.5 per 10,000 among
factor V Leiden heterozygous women using estrogen-
containingcontraceptives(relativerisk,34.7)(96).There-
fore, alternative methods, such as intrauterine devices
(including those containing progestin), progestin-only
pills or implants, and barrier methods should be used
(97). However, screening all women for thrombophilias
beforeinitiatingcombinationcontraceptionisnotrecom-
mended(9799).
Summary of
Recommendations and
Conclusions
The following recommendation is based on good
andconsistentscientificevidence(LevelA):
When signs or symptoms suggest new onset DVT,
therecommendedinitialdiagnostictestiscompres-
sionultrasonographyoftheproximalveins.
The following recommendations and conclusions
arebasedonlimitedorinconsistentscientificevi-
dence(LevelB):
Thepreferredanticoagulantsinpregnancyarehepa-
rincompounds.
A reasonable approach to minimize postpartum
bleeding complications is resumption of anticoagu-
lationtherapynosoonerthan46hoursaftervaginal
deliveryor612hoursaftercesareandelivery.
Becausewarfarin,LMWH,andunfractionatedhepa-
rin do not accumulate in breast milk and do not
induce an anticoagulant effect in the infant, these
anticoagulantsarecompatiblewithbreastfeeding.
The following recommendations are based pri-
marilyonconsensusandexpertopinion(LevelC):
Women with a history of thrombosis who have not
had a complete evaluation of possible underlying
etiologiesshouldbetestedforbothantiphospholipid
antibodiesandforinheritedthrombophilias.
Therapeutic anticoagulation is recommended for
womenwithacutethromboembolismduringthecur-
rentpregnancyorthoseathighriskofvenousthrom-
boembolism,suchaswomenwithmechanicalheart
valves.
When reinstitution of anticoagulation therapy is
plannedpostpartum,pneumaticcompressiondevices
shouldbeleftinplaceuntilthepatientisambulatory
anduntilanticoagulationtherapyisrestarted.
Womenreceivingeithertherapeuticorprophylactic
anticoagulation may be converted from LMWH to
theshorterhalf-lifeunfractionatedheparininthelast
month of pregnancy or sooner if delivery appears
imminent.
VOL. 118, NO. 3, SEPTEMBER 2011 Practice BulletinThromboembolism in Pregnancy 725
Canada. Maternal Health Study Group of the Canadian
Perinatal Surveillance System. J Obstet Gynaecol Can
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10. ClarkSL,BelfortMA,DildyGA,HerbstMA,MeyersJA,
HankinsGD.Maternaldeathinthe21stcentury:causes,
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11. ProgramforAppropriateTechnologyinHealth(PATH).
Postpartum hemorrhage prevention and treatment: post-
partumhemorrhage.Availableat:http://www.pphpreven-
tion.org/pph.php.RetrievedApril19,2011.(LevelIII)
12. ChangJ,Elam-EvansLD,BergCJ,HerndonJ,FlowersL,
SeedKA,etal.Pregnancy-relatedmortalitysurveillance--
UnitedStates,1991--1999.MMWRSurveillSumm2003;
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13. Blanco-Molina A, Rota LL, Di Micco P, Brenner B,
Trujillo-SantosJ,Ruiz-GamieteaA,etal.Venousthrom-
boembolism during pregnancy, postpartum or during
contraceptiveuse.RIETEInvestigators.ThrombHaemost
2010;103:30611.(LevelII-3)
14. GordonMC.Maternalphysiology.In:GabbeSG,Niebyl
JRandSimpsonJL,editors.Obstetrics:normalandprob-
lem pregnancies. 5th ed. Philadelphia (PA): Churchill
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study of gestational and postural changes in the deep
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Gynaecol1997;104:1917.(LevelIII)
16. WhittyJE,DombroswkiMP.Respiratorydiseasesinpreg-
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Philadelphia(PA):ChurchillLivingstone;2007.p.93963.
(LevelIII)
17. Danilenko-DixonDR,HeitJA,SilversteinMD,YawnBP,
PettersonTM,LohseCM,etal.Riskfactorsfordeepvein
thrombosisandpulmonaryembolismduringpregnancyor
postpartum:apopulation-based,case-controlstudy.AmJ
ObstetGynecol2001;184:10410.(LevelII-3)
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Adashek JA. Prolonged bedrest during pregnancy: does
the risk of deep vein thrombosis warrant the use of
routine heparin prophylaxis? J Matern Fetal Med 1997;
6:2647.(LevelII-3)
19. KovacevichGJ,GaichSA,LavinJP,HopkinsMP,Crane
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It is recommended to withhold neuraxial blockade
for 1012 hours after the last prophylactic dose of
LMWH or 24 hours after the last therapeutic dose
ofLMWH.
Placementofpneumaticcompressiondevicesbefore
cesarean delivery is recommended for all women
notalreadyreceivingthromboprophylaxis.
Proposed Performance
Measure
Percentage of patients assessed for risk factors for
thrombosisatthebeginningofpregnancy,duringpreg-
nancy,andatthetimeofdelivery
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The MEDLINE database, the Cochrane Library, and the
American College of Obstetricians and Gynecologists
own internal resources and documents were used to con-
ductaliteraturesearchtolocaterelevantarticlespublished
between January 1985December 2010. 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 commentaries also
were consulted. Abstracts of research presented at sympo-
siaandscientificconferenceswerenotconsideredadequate
for inclusion in this document. Guidelines published by
organizationsorinstitutionssuchastheNationalInstitutes
of Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
fromobstetriciangynecologistswereused.
Studieswerereviewedandevaluatedforqualityaccording
to the method outlined by the U.S. Preventive Services
TaskForce:
I Evidence obtained from at least one properly
designedrandomizedcontrolledtrial.
II-1 Evidence obtained from well-designed controlled
trialswithoutrandomization.
II-2 Evidence obtained from well-designed cohort or
casecontrolanalyticstudies,preferablyfrommore
thanonecenterorresearchgroup.
II-3 Evidenceobtainedfrommultipletimeserieswithor
withouttheintervention.Dramaticresultsinuncon-
trolled experiments also could be regarded as this
typeofevidence.
III Opinionsofrespectedauthorities,basedonclinical
experience,descriptivestudies,orreportsofexpert
committees.
Based on the highest level of evidence found in the data,
recommendationsareprovidedandgradedaccordingtothe
followingcategories:
Level ARecommendations are based on good and con-
sistentscientificevidence.
LevelBRecommendationsarebasedonlimitedorincon-
sistentscientificevidence.
Level CRecommendations are based primarily on con-
sensusandexpertopinion.
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409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Thromboembolisminpregnancy.PracticeBulletinNo.123.American
College of Obstetricians and Gynecologists. Obstet Gynecol 2011;
118:71829.