Venous thromboembolism (VTE) Venous thromboembolism (VTE) in obstetricsin obstetrics

Dr. Yasir Katib

MBBS, FRCSC, Perinatologist

ObjectivesObjectives

IncidencePathogenesisPredisposing factorsProphylaxisManagement choices

– Antepartum– Postpartum

IncidenceIncidence

Deep venous thrombosis– antepartum: 0.5-3 per 1000 pregnancies– postpartum: 0.5-18 per 1000 pregnancies

High recurrent risk: 7-13%pulmonary embolus

– untreated DVT: 24% have PE, 15% mortality

– treated DVT: 5% have PE, 1-2% mortality

Number of pregnancy deaths from 1982-1992 in Canada

0

2

4

6

8

10

12

14 PE

postpartumhemorrhage

amniotic fluidemboli

preeclampsia

anesthetics

ectopicpregnancy

septicemia

undetermined

Fatal Maternal PE 1994-2005

1715

21

15

33

8

12

0

5

10

15

20

25

30

35

1st 2nd 3rd 1 2 3 & 4 5 & 6

Num

ber

of d

eath

s

Total

Normal delivery

Caesarean

Antenatal

Postpartum weekAntenatal trimester

Data from CEMACH Maternal deaths enquiries, UK. Slide courtesy Peter MacCallum

Pathogenesis of VTE in pregnancyPathogenesis of VTE in pregnancy

Stasis Hypercoagulation

Vessel wall abnormality

Predisposing factors associated with Predisposing factors associated with pregnancypregnancy

Hypercoagulability Stasis Endothelial damage

Increased factors: II, V, VII, VIII, IX, X, XII, fibrinogen

Increased venous distensibility and decreased tone

Vascular damage at delivery (CS or operative vaginal deliveries)

Increased platelet aggregation 50% decrease in venous flow in lower extremity by 3rd trimester

Decreased protein S, tissue plasminogen activator, factor XI, XIII

Uterus is mechanical impediment to venous return

Increased resistance to activated protein C

Decreased or normal antithrombin

Risk factor for VTE OR 95% CIPrevious VTE 1 24.8 17.1-36

Age > 35 4

1.3 1.0-1.7

BMI > 30 2

15.34.4

2.1-13.53.4-5.7

Smoking 3 2.7 1.5-4.9

Parity >3 4 2.4 1.8-3.1

Medical Conditions1

Sickle cell disease, SLE, Heart disease, anaemia, infection, Hyperemesis

2.0 – 8.7

2.51 2.0-3.2

Immobility 3 7.7 (an)10.8 (pn)

3.2-194-28.8

Pre-eclampsia3

+Fetal Growth Restriction3.15.8

1.8-5.32.1-16

Assisted reproductive therapy 4.3 2.0-9.4

Twins3 2.6 1.1-6.2

APH 1 2.3 1.8-2.8

Post partum haemorrhage 4.1 2.3-7.3

Caesarean section 4 3.6 3.0-4.3

Varicose veins 2.4 1.04-5.4

Transfusion1 7.6 6.2-9.4

1.James et al 2006; 2.Larsen et al 2007; 3.Jacobsen et al 2008; 4.Lindqvist et al 1999

ThrombophiliasThrombophilias

Congenital:– resistance to activated protein C (factor V leiden)– hyperhomocysteinemia (controversial)– protein S, C deficiency: 2-4% risk, 18-20% risk

during postpartum – antithrombin III deficiency: 25-55% risk

Acquired:– antiphospholipid syndrome (APLS): role to

cause VTE is uncertain

Prevalence in population Prevalence in population

General population Thrombosis

Factor V leiden 5-9% 20-40%

Prothrombin G20210A

3% 6-15%

Protein C def 0.3% 1-2%

Protein S 0.2% 1-2%

ATIII def 0.07% <1%

Hyperhomocystin-emia

5% 5-10%

Obstetrical complications of Obstetrical complications of thrombophiliathrombophiliaThere is growing evidence to suggest

that the incidence of thrombophilias is also increased in women with

1. Late fetal loss (abortions)

2. Gestational hypertension

3. Intrauterine growth restriction

4. IUFD

Recommendations for thromboprophylaxisRecommendations for thromboprophylaxis

Antepartum all pregnant women who had previous VTE should be tested

for thrombophilia factors; for single episode of prior VTE with transient risk factors:

surveillance (1C) for single episode of idiopathic VTE: surveillance or UFH or

prophylactic LMWH dose (1C) for single episode of VTE and thrombophilia (except protein

S): surveillance (except decreased antithrombin) or UFH or prophylactic LMWH dose (1C)

Recommendations for thromboprophylaxisRecommendations for thromboprophylaxis

Women with asymptomatic inherited or acquired thrombophilia may be managed with close surveillance antenatally.

Exceptions are women with antithrombin deficiency, those with more than one thrombophilic defect (including homozygosity for factor V Leiden) or those with additional risk factors where advice of a local expert should be sought and antenatal prophylaxis considered

Antepartum continues:Antepartum continues:

known thrombophilia: surveillance (except decreased antithrombin) or UFH or prophylactic LMWH dose (1C)

recurrent episodes of VTE: adjusted dose of UFH or adjusted dose of LMWH (1C)

> 3 moderate risk factors: surveillance or UFH or prophylactic LMWH dose (1C)

Postpartum thromboprophylaxisPostpartum thromboprophylaxis

All women with class 3 obesity (BMI > 40kg/m2) should be considered for thromboprophylaxis with LMWH for 7 days after delivery. GPP

All women with asymptomatic heritable or acquired thrombophilia should be considered for LMWH for at least seven days following delivery, even if they were not receiving antenatal thromboprophylaxis.

This should be extended to 6 weeks if there is a family history or other risk factors present.

Grade C

Summary of protocol for thromboprophylaxis in women with previous VTE and/or thrombophiliaThese women require joint specialist management by obstetricians and experts in haemostasis and pregnancy

Very High RiskPrevious VTE (+/- thrombophilia) on long term warfarinAntithrombin deficiencyAntiphospholipid syndrome

Antenatal high prophylactic or therapeutic dose LMWH and at least six weeks postnatal warfarin.

High Risk Previous recurrent or unprovoked VTE Previous estrogen (pill / pregnancy) associated VTE

Previous VTE + thrombophilia Antenatal and six weeks postnatal prophylactic LMWH

Previous VTE + family history of VTE

Asymptomatic thrombophilia (combined defects, homozygous FVL or prothrombin gene defect)

Moderate Risk Single previous provoked VTE associated with transient risk factor no longer present without thrombophilia, family history or other risk factors

Six weeks postnatal prophylactic LMWH

Seven days postnatal LMWH extended to six weeks if family history +ve, other risk factors

Asymptomatic thrombophilia (except AT deficiency, combined defects, homozygous FVL or prothrombin gene defect)

Prophylactic doses of UFH and Prophylactic doses of UFH and LMWHLMWH UFH 5000 IU sc bid

Prophylactic LMWH: Enoxaparin 40 mg sc q24h, Dalteparin 5000 IU sc q24h. Anti–factor Xa assay: 0.2 and 0.6 U/mL 4 hours

after the injection

IV HeparinIV Heparin

– inhibits thrombin by activating AT-III, prevents conversion of fibrinogen to fibrin

– need baseline CBC, INR PTT– initial 5000 IU bolus, then 1000-1500 IU/hr,

INR & PTT q6hr PTT therapeutic level 1.5-2.5, then INR/PTT q24h

Advantages:– doesn’t cross placenta– not excreted in breast milk

IV HeparinIV Heparin

– rapidly reversible (protamine sulfate 1mg/100units)

– no increase in Perinatal mortality or morbidity over control

Disadvantages:– bleeding in 4-8%– osteoporosis (15,000U/d > 5 months)– thrombocytopenia (by day 4)– Cost and compliance

Low molecular weight heparinLow molecular weight heparin

Adjusted dose LMWH: Enoxaparin 1 mg/kg sc q12h, Dalteparin 200 IU/kg sc q24h

Advantages:

• possibly less risk of– thrombocytopenia– osteoporosis

more predictable therapeutic effect

monitor anti-Xa levels in third trimester

Disadvantages:

more difficult to reverse

drug cost higher but no need for hospitalization

Low molecular weight heparin

CoumadinCoumadin

easily crosses placenta up to 70% fetal complications if in 1st

trimester– IUGR, chondrodysplasia punctata– multiple congenital anomalies

20-30% complication rate in 2nd-3rd trimester

Long half life

Management during peripartumManagement during peripartum

Therapy throughout pregnancy and 8-12 weeks post partum

IV Heparin and LMWH should be held once labor is established in order to use local anesthesia

If therapeutic PTT is required in labor, patient should be switched to IV heparin, and local anesthesia is contraindicated

therapeutic PTT may increase the incidence of hematomas but not PPH

Avoid trauma or C/S at delivery–midline episiotomy if necessary–avoid tears

Resume heparin 6 hrs postpartum Start coumadin when oral intake tolerated Avoid OCP, estrogen Consult!

Management during peripartum

Take home messageTake home message Thromboprophylaxis is recommended for previous

VTE hx and a known thrombophilia; idiopathic VTE, recurrent VTE, and more than 3 major risk factors for VTE (II B)

Diagnosis of VTE is clinical suspicion + lab tests, never hesitate to order V/Q scan or angiography if the result will change management

Treatment is long term: till postpartum 8-12 weeks. Considering side effects of different drugs, cost, local anesthesia, avoiding instrument delivery

Take home messageTake home message

Extended use of LMWH– Increased number of risk factors– Focus on admitted patients

Importance of estrogen related prior events Extended duration of LMWH post partum

from 3-5 days to 7 days