Tromboembolismo en Embarazo 2011

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718 VOL. 118, NO. 3, SEPTEMBER 2011 OBSTETRICS & GYNECOLOGY

PRACTICE

BULLETIN

the american college of obstetricians and gynecologists

women ’ s health care physicians

BackgroundDeepveinthrombosis(DVT)andpulmonaryembolism

(PE)arecollectivelyreferredtoasvenousthromboem-

bolicevents.Approximately75–80%ofcasesofpreg-

nancy-associatedvenous thromboembolism are caused

byDVT,and20–25%ofcasesarecausedbyPE(3,7,

13).Onehalfoftheseeventsoccurduringpregnancyand

onehalfoccurduringthepostpartumperiod(3–8).

Pregnancy-Associated Changes and Venous Thromboembolism

Pregnancyisassociatedwithphysiologicandanatomic

changes that increase the risk of thromboembolism,including hypercoagulability, increased venous stasis,

decreasedvenousoutflow(14,15),compressionofthe

inferior vena cava and pelvic veins by the enlarging

uterus(16),anddecreasedmobility(17–20).Pregnancy

altersthelevelsofcoagulationfactorsnormallyrespon-

sibleforhemostasis.Theoveralleffectofthesechanges

isanincreasedthrombogenicstate(seeTable1).When

DVT occurs during pregnancy, it is more likely to

involvetheleftlowerextremity(21–23).

Risk Factors

Theriskofvenousthromboembolismmaybehigherin

the thirdtrimester comparedwiththe firstand second

trimesters(2), but theincreasedrisk ofvenousthrom-

boembolismispresentfromthefirsttrimester(22,23),

oftenbeforemanyoftheanatomicchangesofpregnancy

occur. The risk ofvenousthromboembolismis 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 0.5–2.0 per

1,000 pregnant women (4–9). 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 obstetrician –gynecologists

Committee on Practice Bulletins—Obstetrics.ThisPracticeBulletinwasdevelopedbytheCommitteeonPracticeBulletins—Obstetricswiththeassis-

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, 1.6–7.8),

and 15–25% ofall casesofvenous 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 in20–50%

of women who experience venous thromboembolism

duringpregnancyandthepostpartumperiod(25).Both

acquiredandinheritedthrombophiliasincreasetherisk

ofvenousthromboembolism(26).

Besides a personal history of thrombosis, other

risk factors for the development of pregnancy-associ-

atedvenous thromboembolism include thephysiologic

changes that accompany pregnancy and childbirth,

medical factors (such as obesity, hemoglobinopathies,

hypertension, and smoking), and pregnancy complica-

tions(includingoperativedelivery)(3,6–8,17,27,28).

Anticoagulation Medications inPregnancy

Theuseofanticoagulationtherapyinwomenduringpreg-

nancywarrantsspecialconsiderationforbothmotherand

fetus.Mostwomenwhorequireanticoagulationtherapy

beforeconceptionwillneedtocontinuethistherapydur-

ingpregnancyandthepostpartumperiod.Commonanti-

coagulationmedications include unfractionated heparin,

low molecularweight heparin (LMWH), and warfarin.

The preferred anticoagulants in pregnancy are heparin

compounds.

Heparin Compounds

NeitherunfractionatedheparinnorLMWHcrossesthe

placenta(29,30)andbothareconsideredsafeinpreg-

nancy(31).Uniqueconsiderationsregardingtheuseof

anticoagulationtherapyinpregnancyincludea40–50%

increaseinmaternalbloodvolume;anincreaseinglo-

merularfiltration,whichresultsinincreasedrenalexcre-

tionof heparin compounds;andan increase inprotein

bindingofheparin(32).Duringpregnancy,bothunfrac-

tionatedheparinandLMWHhaveshorterhalf-livesand

lowerpeakplasmaconcentrations,usuallynecessitating

higherdosesandmorefrequentadministrationinorder

tomaintaineffectiveconcentrations(33–39).

Therearefewcomparativestudiesof LMWHuse

inpregnancy,butinnonpregnantpatients,LMWHhasbeenassociatedwithfeweradverseeffectsthanunfrac-

tionatedheparin (40).Potentialadvantagesof 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 associatedwith significant bone loss when used

inprophylacticdosesduringpregnancy(43–45).Unfrac-

tionated heparin, which is associated with increased

bruising at the injectionsites,also hasbeen associated

with other skin reactions and serious allergic reactions(46). Moreover, unfractionated heparin is dispensed in

multiple-dosevials,which are potentially vulnerable to

contamination (47). Besides its greater cost, a relative

disadvantageofLMWHatthetimeofdeliveryisitslon-

gerhalf-life,whichisanimportantconsiderationforboth

neuraxialanesthesiaandperipartumbleedingrisk.

Warfarin

Warfarin,acommonagentforlong-termanticoagulation

therapyoutsideofpregnancy,hasbeenassociatedwith

potentially harmful fetal effects, especially with first-

trimesterexposure(48–54).Warfarinembryopathyhasbeenlinkedwithexposureat6–12weeksofgestation,

highlightingtheimportanceofearlypregnancycarein

suchpatients(55).Therefore,formostwomenreceiving

prolonged anticoagulation therapy who become preg-

nant,it is recommendedthatunfractionatedheparinor

LMWHbeusedinplaceofwarfarin.

Althoughrarelyprescribedinpregnancy,warfarinis

stillconsideredinpregnancyforwomenwithmechani-

calheartvalvesbecauseoftheirhighriskofthrombosis

Table 1. Changes in the Normal Functioning of theCoagulation 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 BremmeKA. Haemostatic changes in pregnancy. Best Practice &ResearchClinicalHaematology.2003;16:153–68 and MedcalfRL,StasinopoulosSJ.Theundecidedserpin:theinsandoutsofplasminogenactivatorinhibitortype2.FEBSJ2005;272:4858–67.



720 Practice Bulletin Thromboembolism in Pregnancy OBSTETRICS & GYNECOLOGY

even with heparin or LMWH anticoagulation therapy

(56).Themanagementofsuchwomenrequiresamulti-

disciplinary care approach, and the decision regarding

optimalanticoagulationtherapymeritsadetaileddiscus-

sionwiththepatientandherhealthcareprovidersregard-

ingtherisksandbenefitsofthevarioustreatmentoptions.

Clinical Considerations andRecommendations

Whatistheappropriateevaluationofwomen

withapriorvenousthromboembolism?

Womenwithahistoryofthrombosiswhohavenothad

acompleteevaluationofpossibleunderlyingetiologies

should be tested for both antiphospholipid antibodies

(57)and for inherited thrombophilias (58).The results

ofthrombophiliatestinginwomenwithapriorvenous

thromboembolismmay alter the need for treatment ortheintensityoftreatmentfromaprophylactictoathera-

peutic dose (also known as adjusted-dose or weight-

baseddose)ofLMWHorunfractionatedheparin(59).

Howisavenousthromboembolism

diagnosedinpregnancy?

Deep Vein Thrombosis

ThetwomostcommoninitialsymptomsofDVT,present

inmorethan80%ofwomenwithpregnancy-associated

DVT, are pain and swelling in an extremity (23). A

differenceincalfcircumferenceof2cmormoreispar-ticularlysuggestive ofDVT in a lower extremity (60).

When signs or symptoms suggestnew-onsetDVT, the

recommendedinitialdiagnostictestiscompressionultra-

sonographyoftheproximalveins(40).Whenresultsare

negativeandiliacveinthrombosisisnotsuspected,rou-

tinesurveillancemaybeareasonableoption(seeFig.1).

When results are negative or equivocal and iliac vein

thrombosisissuspected,additionalconfirmatoryimaging

withmagneticresonanceimagingisrecommended(61).

Alternatively, depending on the clinical circumstances,

empiricanticoagulationmaybeareasonableoption(see

Fig.1).AlthoughmeasurementofD-dimerlevelsisause-fulscreeningtooltoexcludevenousthromboembolismin

the nonpregnant population, pregnancy is accompanied

byaprogressiveincreaseinD-dimerlevels,evenahigh

D-dimerleveldoesnotpredictvenousthromboembolism

inpregnancy(62–64).

Pulmonary Embolism

The diagnosis of new-onset PE is similar to that in

thenonpregnant individual.Both ventilation–perfusion

scanning and computed tomographic (CT) angiogra-

phy are associatedwith relatively low radiation expo-

sure for the fetus (65). The concerns about maternal

breastradiationexposurewithCTangiographymustbe

weighedagainstthepotentialconsequencesofwithhold-

ing appropriate imaging and failing tomake a proper

diagnosis.ArecentstudyconcludedthatachestX-ray

couldbeusedasadiscriminatortoreducethelikelihood

ofnondiagnosticventilation–perfusionscanningandCT

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

womenwith a historyof thrombosis or those who are

at significant risk of venous thromboembolism during

pregnancyorthepostpartumperiod,suchasthosewith

Suspect lowerextremity deep vein thrombosis

Compressionultrasonography oflower extremity or

extremities

Results

Negative orequivocal and

suspect iliac vesselprocess

Additional

imaging studies

Presumptive

anticoagulationtherapy

Results

Routinesurveillance

Treat

Fig. 1.Diagnosisofdeepveinthrombosisduringpregnancy.FigureprovidedcourtesyofLeoR.Brancazio,MD.

Negative anddo not suspect

iliac vesselprocess

Positive

Positive

Negative




high-risk acquired or inherited thrombophilias (see

Table2).

Despite the increased risk of venous thromboem-

bolism during pregnancy and the postpartum period,

routineanticoagulationtherapyforallpregnantwomen

isnot warranted (67, 68).Bleedingcomplications can

arise from administration of unfractionated heparin or

LMWH, and this complication should be consideredbeforeinitiatinganticoagulationtherapy(31,41,69,70).

Howshouldanticoagulationtherapybe

administered?

Therearenolargetrialsregardingtheoptimaldoseof

anticoagulants inpregnancy,and recommendations for

theiruse are based oncase series and expert opinion.

Therapeuticanticoagulationisrecommendedforwomen

with acute thromboembolism during the current preg-

nancyorthoseathighriskofthrombosis,suchaswomen

withmechanicalheartvalves(40).Thedecisionregard-

ingintensityoftreatmentmaybeshapedbyotherrisk

factorssuchascesareandelivery,prolongedimmobility,

obesity,andfamilyhistoryofthrombophiliasorvenousthromboembolism (see Table 3). For women with a

historyofidiopathicthrombosisorthosewithtransient

riskfactorswhoarenottakinganticoagulantsasalife-

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 episodeofVTE––Notreceivinglong-term orsurveillancewithoutanticoagulation intermediate-doseLMWH/UFHanticoagulationtherapy therapy

High-riskthrombophilia§withoutpreviousVTE ProphylacticLMWHorUFH Postpartumanticoagulationtherapy

High-riskthrombophilia§withasingleprevious Prophylactic,intermediate-dose,oradjusted- Postpartumanticoagulationtherapyor episodeofVTE––Notreceivinglong-term doseLMWH/UFHregimen intermediateoradjusted-doseLMWH/UFHforanticoagulationtherapy 6weeks(therapylevelshouldbeatleastas highasantepartumtreatment)

Nothrombophiliawithprevioussingle Surveil lancewithoutanticoagulat ion Postpartumanticoagulat iontherapyII

episodeofVTEassociatedwithtransient therapy

riskfactorthatisnolongerpresent— Excludespregnancy-orestrogen-related riskfactor

Nothrombophiliawithprevioussingle Prophylactic-doseLMWHorUFHII PostpartumanticoagulationtherapyepisodeofVTEassociatedwithtransientrisk factorthatwaspregnancy-orestrogen-related

Nothrombophiliawithprevioussingleepisode Prophylactic-doseLMWHorUFHII PostpartumanticoagulationtherapyofVTEwithoutanassociatedriskfactor (idiopathic)—Notreceivinglong-termanticoagulationtherapy

Thrombophiliaornothrombophiliawithtwo Prophylacticortherapeutic-doseLMWH PostpartumanticoagulationtherapyormoreepisodesofVTE—Notreceivinglong- or ortermanticoagulationtherapy Prophylacticortherapeutic-doseUFH Therapeutic-doseLMWH/UFHfor6weeks

Thrombophiliaornothrombophiliawithtwo Therapeutic-doseLMWHorUFH Resumptionoflong-termanticoagulationormoreepisodesofVTE—Receivinglong-term therapyanticoagulationtherapy

Abbreviations:LMWH,lowmolecularweightheparin;UFH,unfractionatedheparin;VTE,venousthromboembolism.

*Postpartumtreatmentlevels should begreateror equalto antepartum treatment. Treatment of acuteVTE andmanagementofantiphospholipidsyndromeareaddressedinotherPracticeBulletins.†Low-riskthrombophilia:factorVLeidenheterozygous;prothrombin G20210Aheterozygous;proteinCorproteinSdeficiency.‡First-degreerelativewithahistoryofathromboticepisodebeforeage50years,orothermajorthromboticriskfactors(eg,obesity,prolongedimmobility).§High-riskthrombophilia:antithrombindeficiency;doubleheterozygousfor prothrombinG20210AmutationandfactorVLeiden;factorVLeidenhomozygousorprothrombinG20210Amutationhomozygous.||Surveillancewithoutanticoagulationissupportedasanalternativeapproachbysomeexperts.




66%ofwhomreceivedoncedailyLMWH(71).Another

studycomparingoncedailytinzaparinversustwicedaily

tinzaparinforthetreatmentofvenousthromboembolism

inpregnancyfoundthatahigher-than-recommendeddos-

agewasrequiredtomaintainanti-Xaactivityinthetarget

rangeinwomenwhotooktinzaparinonlyonceaday(36).

Anotherretrospectivestudyoftheonce-a-daytinzaparin

regimen found two unusual thrombotic complicationsamong37pregnancies(72).Anyadjustmentforobesityis

incorporatedintotherapeutic-doseregimens.Thereisno

evidenced-basedprotocolforadjustingprophylacticdoses

inwomenwhoareobese,thusadjustmentscanbemade

onacase-by-casebasis.

Whichanticoagulantsshouldbeusedin

casesofheparinallergy?

In cases of severe cutaneous allergies or heparin-

induced thrombocytopenia in pregnancy, fondaparinux

(asyntheticpentasaccharide)maybethepreferredanti-

coagulantbecausedanaparoid,anLMWHwithminimal

cross-reactivityinheparin-sensitivepatients,iscurrently

unavailableintheUnitedStates(73).However,thereare

insufficientdatatojustifytheroutineuseoffondaparinux

asanalternativeto heparinsforprophylaxisofvenous

thromboembolisminpregnancy.Althougharecentretro-

spectivestudycomparingfondaparinuxwithenoxaparin

administeredbetweenday6oftheconceptioncycleand

continueduntil12weeksofgestationfoundnountoward

effectsoffondaparinuxonmotherorinfant(74),antico-

agulantactivityhasbeendetectedinumbilicalcordblood

ofexposedfetuses(75).

Howisnewlydiagnosedvenousthromboem-

bolisminpregnancymanaged?

Management ofnewly diagnosed venous thromboem-

bolismrequirestherapeuticanticoagulationwitheither

unfractionatedheparinorLMWH(Table3).Hospital-

ization for the initiation of anticoagulation therapy

may be indicated in cases of hemodynamic instabil-

ity,largeclots,ormaternalcomorbidities.Intravenous

unfractionatedheparincanbeconsideredintheinitial

treatment of PE and in situations in which delivery,

surgery,orthrombolysis(indicatedforlife-threateningorlimb-threateningthromboembolism)maybenecessary.

When patients appear to be hemodynamically stable,

therapeuticLMWHcanbesubstitutedinanticipationof

dischargefromthehospital.

Howshouldanticoagulationtherapybe

monitoredduringpregnancy?

Dataareunclearregardingoptimalsurveillanceofanti-

coagulation therapy during pregnancy. When used in

andpostpartumprophylaxis(40).Patientswithan inci-

dentally discovered low-risk thrombophilia who have

nothadapriorvenousthromboembolismcanbeman-

agedantepartumwitheithersurveillanceorprophylactic

LMWHorunfractionatedheparin,andinthepostpartum

periodwith either LMWH and unfractionated heparinprophylaxis orwith surveillance if the patient hasno

additionalriskfactorsforDVT.

Basedonthepharmacokineticsoftheheparinagents

inpregnancy,therapeuticLMWHshouldbeadministered

onceortwicedailyandunfractionatedheparin,every12

hours (Table3)(34–38).A retrospective studyofonce

daily versus twice daily doses of various heparins for

venous thromboembolisminpregnancy 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/kgoncedailyweight-adjusted, Tinzaparin,175units/kgoncedailyfull-treatmentdose) Dalteparin,100units/kgevery12hours

MinidoseprophylacticUFH UFH,5,000unitsSCevery12hours

ProphylacticUFH UFH,5,000–10,000unitsSCevery 12hours

UFH,5,000–7,500unitsSCevery 12hoursinfirsttrimester

UFH,7,500–10,000unitsSCevery 12hoursinthesecondtrimester

UFH,10,000unitsSCevery12hours inthethirdtrimester,unlesstheaPTT iselevated

TherapeuticUFH UFH,10,000unitsormoreSCevery (Alsoreferredtoas 12hoursindosesadjustedtotargetweight-adjusted, aPTTinthetherapeuticrange(1.5–2.5,ful l-treatmentdose) 6hoursafter injection)

Postpartumanticoagulation ProphylacticLMWH/UFHfor4–6weeks or VitaminKantagonistsfor4–6weeks withatargetINRof2.0–3.0,withinitial UFHorLMWHtherapyoverlapuntilthe INRis2.0ormorefor2days

Surveillance‡

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

*Althoughatextremesofbodyweight,modificationofdosemayberequired.†Maytargetananti-Xalevelinthetherapeuticrangeof0.6–1.0units/mLfortwicedailyregimen;slightlyhigherdosesmaybeneededforaonce-dailyregimen.‡Clinicalvigilanceandappropriateobjectiveinvestigationofwomenwithsymp-tomssuspiciousofdeepveinthrombosisorpulmonaryembolismmaybeneeded.




therapeuticdosestotreatorpreventvenousthromboem-

bolism,itisnotclearwhetherthedoseofLMWHneeds

tobeadjusted.Onthebasisofsmallstudiesdemonstrat-

ingtheneedforincreasedLMWHtomaintainantifactor

Xalevelsbetween0.6units/mLand1.0units/mL,some

advocateperiodicmeasurement ofantifactorXa levels

4–6hoursafterinjection,butotherstudieshaveshown

thatfewwomenactuallyrequireincreaseddoseswhenweight-baseddosesareused(40).Patientsconvertedtoa

subcutaneoustherapeuticdoseofunfractionatedheparin

inthelastmonthofpregnancyshouldhaveanactivated

partial thromboplastin time (aPTT) checked (aPTT of

1.5–2.5,6hoursafterinjection)andtheirdoseofheparin

adjustedtomaintaintheaPTTinthetherapeuticrange.

Patients receiving prophylactic anticoagulation do

not requiremonitoring,butmeasurement of antifactor

XalevelsoraPTTmaybewarrantedincasesinwhich

prophylaxislevelsoutsideoftherecommendedrangeare

clinically suspected (39). In one study, approximately

40%ofwomentakingprophylacticLMWHhadlevelsoutsideoftheprophylacticrange(39).

Guidelines recommend obtaining platelet counts

wheninitiatingtherapeuticunfractionatedheparintherapy

inordertomonitorforheparin-inducedthrombocytopenia

(76).Thedataarelessclearaboutmeasuringplateletlev-

elswheninitiatingLMWH,butcasereportsofheparin-

inducedthrombocytopeniahavebeendescribed(77).

Howisanticoagulationtherapymanagedat

thetimeofdelivery?

Women receiving either therapeutic or prophylactic

anticoagulationtherapymaybeconvertedfromLMWH

totheshorterhalf-lifeunfractionatedheparininthelast

monthofpregnancyorsoonerifdeliveryappearsimmi-

nent.Analternative optionmaybe to stoptherapeutic

anticoagulationandinducelaborwithin24hours,ifclin-

icallyappropriate.Thepurposeofconversiontounfrac-

tionatedheparinhaslesstodowithanyriskofmaternal

bleedingatthetimeofdelivery,butrathertheriskofan

epidural or spinal hematomawith regional anesthesia.

TheAmericanSocietyofRegionalAnesthesiaandPain

Medicineguidelines recommendwithholdingneuraxial

blockade for 10–12 hours after the last prophylactic

dose ofLMWHor24 hours after the last therapeuticdoseofLMWH(78).Theseguidelinessupporttheuse

ofneuraxialanesthesiainpatientsreceivingdosagesof

5,000unitsofunfractionatedheparintwicedaily,butthe

safetyinpatientsreceiving10,000unitstwicedailyor

moreisunknown.Insuchcases,theAmericanSociety

ofRegionalAnesthesiaandPainMedicinerecommends

assessmentonanindividualbasis(78).Ifawomangoes

intolaborwhiletakingunfractionatedheparin,clearance

canbeverifiedbyanaPTT.Reversalofheparinisrarely

requiredandisnotindicatedwithaprophylacticdoseof

heparin. For women in whom anticoagulation therapy

hastemporarilybeendiscontinued,pneumaticcompres-

sionsdevicesarerecommended.

Shouldpatientsundergoingcesareandelivery

receiveDVTprophylaxis?

Cesarean delivery approximately doubles the risk of

venousthromboembolism(6),butintheotherwisenormal

patient, this risk is still low (approximately1 per1,000

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

poweredto assess adecreasein the riskofDVTor PE

with anticoagulation therapy (80–82). One published

decision analysis concluded that if thromboprophylaxiswas elected, pneumatic compression devices were pre-

ferred to unfractionated heparin because of the risk of

bleeding complicationsand heparin-induced thrombocy-

topenia (83). Another decision analysis concluded that

pneumaticcompressiondeviceswerecosteffectiveifthe

incidence of postcesarean venous thromboembolism in

thepopulationwasatleast6.8per1,000patients(84).

Forpatientsundergoingcesareandeliverywithaddi-

tionalriskfactorsfor thromboembolism,individualrisk

assessmentmay require thromboprophylaxiswithboth

pneumaticcompressiondevicesandunfractionatedhepa-

rin orLMWH(40).However,cesarean deliveryin theemergency setting should not be delayed because of

thetimingnecessaryto implementthromboprophylaxis.

Mostpatientsreceivingthromboprophylaxisduringpreg-

nancywillbenefitfrompostpartumthromboprophylaxis,

butthedoseandroutewillvarybyindication(85).

Additionalmeasuresshouldbe considered forcer-

tain women at particularly high risk of thrombosis at

the time of delivery. Women who have antithrombin

deficiencymay becandidatesfor antithrombin concen-

tratesperipartum.WomenwhohavehadDVTinthe2–4

weeksbeforedeliverymaybecandidatesforplacement

ofaretrievablevenacavalfilter,withremovalpostpar-tum(86,87).Otherwomenwhomaybecandidatesfor

vena caval filter placement during pregnancy include

womenwithrecurrentvenousthromboembolismdespite

therapeuticanticoagulation(87).

Whenistheoptimaltimetoresumeanti-

coagulationtherapypostpartum?

The optimal time to restart anticoagulation therapy

postpartum isunclear.A reasonable approach tomini-




mizebleedingcomplicationsis torestartunfractionated

heparinorLMWHnosoonerthan4–6hoursaftervagi-

naldeliveryor6–12hoursaftercesareandelivery.One

studyof95womentreatedwithperipartumenoxaparin

comparedwith303controlsfoundnosignificantincrease

intherateofseverepostpartumhemorrhagewhenenoxa-

parinwasrestartedbetween5hoursand24hoursafter

avaginaldeliveryandbetween12hoursand36hoursafteracesareandelivery(88).Currentrecommendations

byAmericanSocietyofRegionalAnesthesiaandPain

MedicineareforresumptionofprophylacticLMWHno

soonerthan2hoursafterepiduralremoval(78).Because

theoptimalintervalforresumptionoftherapeuticantico-

agulationafterepiduralremovalisunclear,12hoursmay

beareasonableapproach.Whenreinstitutionofantico-

agulationtherapyisplannedpostpartum,pneumaticcom-

pressiondevicesshouldbeleftinplaceuntilthepatientis

ambulatoryanduntilanticoagulationtherapyisrestarted.

Womenwhorequiremorethan6weeksoftherapeu-

ticanticoagulationmaybebridgedtowarfarin(89–91).

Bridgingtowarfarinrequireswomentotaketwoantico-

agulantssimultaneously.Forwomenwhorequireonly6

weeksofanticoagulationtherapypostpartum,theutility

ofwarfarinislimitedbecauseitfrequentlyrequires1–2

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

foratleast3–6monthsdependingonthecircumstances

(92).Becausewarfarin,LMWH,andunfractionatedhep-

arindonotaccumulateinbreastmilkanddonotinduce

ananticoagulanteffectintheinfant,theseanticoagulants

arecompatiblewithbreastfeeding(89,93,94).

Whatpostpartumhormonalcontraceptive

optionsareappropriateforwomenwith

thrombophilias?

The risk of venous thromboembolism among women

takingestrogen-containingoralcontraceptivesincreases

35-foldto99-foldandincreases16-foldamongwomenheterozygous for factor V Leiden and prothrombin

G20210A mutations (95). The annual risk of venous

thromboembolism is 5.7 per 10,000 among factor V

Leidencarriersbutincreasesto28.5per10,000among

factor V Leiden heterozygouswomen 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,screeningallwomenfor thrombophilias

beforeinitiatingcombinationcontraceptionisnotrecom-

mended(97–99).

Summary of

Recommendations andConclusionsThefollowingrecommendationisbasedongood

andconsistentscientificevidence(LevelA):

WhensignsorsymptomssuggestnewonsetDVT,

therecommendedinitialdiagnostictestiscompres-

sionultrasonographyoftheproximalveins.

Thefollowingrecommendationsandconclusions

arebasedonlimitedorinconsistentscientificevi-

dence(LevelB):

Thepreferredanticoagulantsinpregnancyarehepa-

rincompounds.

A reasonable approach to minimize postpartum

bleedingcomplicationsisresumptionofanticoagu-

lationtherapynosoonerthan4–6hoursaftervaginal

deliveryor6–12hoursaftercesareandelivery.

Becausewarfarin,LMWH,andunfractionatedhepa-

rin do not accumulate in breastmilk and do not

induce an anticoagulant effect in the infant, these

anticoagulantsarecompatiblewithbreastfeeding.

The following recommendations are based pri-

marilyonconsensusandexpertopinion(LevelC):

Womenwithahistoryofthrombosiswhohavenot

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

anticoagulationmay be convertedfromLMWHto

theshorterhalf-lifeunfractionatedheparininthelast

month ofpregnancyor sooner if delivery appears

imminent.




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Itisrecommendedtowithholdneuraxialblockade

for10–12hoursafterthelastprophylacticdoseof

LMWHor24hoursafterthelasttherapeuticdose

ofLMWH.

Placementofpneumaticcompressiondevicesbefore

cesarean delivery is recommended for all women

notalreadyreceivingthromboprophylaxis.

Proposed PerformanceMeasurePercentage of patients assessed for risk factors for

thrombosisatthebeginningofpregnancy,duringpreg-

nancy,andatthetimeofdelivery

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Ultrasonographic endometrial thickness for diagnosing




TheMEDLINEdatabase, the CochraneLibrary,and theAmerican College of Obstetricians and Gynecologists’owninternalresourcesanddocumentswereusedtocon-ductaliteraturesearchtolocaterelevantarticlespublishedbetween January 1985–December2010. The search wasrestricted to articles published in the English language.Prioritywasgiven toarticles reportingresultsof original

research, althoughreview articles and commentaries alsowereconsulted.Abstractsofresearchpresentedatsympo-siaandscientificconferenceswerenotconsideredadequatefor inclusion in this document. Guidelines published byorganizationsorinstitutionssuchastheNationalInstitutesofHealthandtheAmericanCollegeofObstetricians andGynecologistswerereviewed,andadditionalstudieswerelocated by reviewingbibliographies of identified articles.Whenreliableresearchwasnotavailable,expertopinionsfromobstetrician–gynecologistswereused.

Studieswerereviewedandevaluatedforqualityaccordingto the method outlined by the U.S. Preventive ServicesTaskForce:

I Evidence obtained from at least one properlydesignedrandomizedcontrolledtrial.

II-1 Evidence obtained from well-designed controlledtrialswithoutrandomization.

II-2 Evidence obtained from well-designed cohort orcase–controlanalyticstudies,preferablyfrommorethanonecenterorresearchgroup.

II-3 Evidenceobtainedfrommultipletimeserieswithorwithouttheintervention.Dramaticresultsinuncon-trolledexperiments alsocouldbe regardedas thistypeofevidence.

III Opinionsofrespectedauthorities,basedonclinicalexperience,descriptivestudies,orreportsofexpertcommittees.

Basedonthehighestlevelofevidencefoundinthedata,recommendationsareprovidedandgradedaccordingtothefollowingcategories:

LevelA—Recommendationsarebasedongoodandcon-sistentscientificevidence.

LevelB—Recommendationsarebasedonlimitedorincon-sistentscientificevidence.

LevelC—Recommendationsarebasedprimarilyoncon-sensusandexpertopinion.

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Thromboembolisminpregnancy.PracticeBulletinNo.123.AmericanCollege of Obstetricians andGynecologists. Obstet Gynecol 2011;118:718–29.

Tromboembolismo en Embarazo 2011

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