Venous thromboembolism (VTE) in obstetrics

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Venous thromboembolism (VTE) in obstetrics

• Dr. Yasir Katib
• MBBS, FRCSC, Perinatologist

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Objectives

• Incidence
• Pathogenesis
• Predisposing factors
• Prophylaxis
• Management choices
• Antepartum
• Postpartum

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Incidence

• 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

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• Number of pregnancy deaths from 1982-1992 in
  Canada

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Postpartum week
Antenatal trimester
Data from CEMACH Maternal deaths enquiries, UK.
Slide courtesy Peter MacCallum
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Pathogenesis of VTE in pregnancy
Stasis
Hypercoagulation
Vessel wall abnormality
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Predisposing factors associated with pregnancy
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Risk factor for VTE OR 95 CI
Previous VTE 1 24.8 17.1-36
Age gt 35 4 1.3 1.0-1.7
BMI gt 30 2 1 5.3 4.4 2.1-13.5 3.4-5.7
Smoking 3 2.7 1.5-4.9
Parity gt3 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) 3.2-19 4-28.8
Pre-eclampsia3 Fetal Growth Restriction 3.1 5.8 1.8-5.3 2.1-16
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
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Thrombophilias

• 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

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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 lt1
Hyperhomocystin-emia 5 5-10
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Obstetrical complications of thrombophilia

• There is growing evidence to suggest that the
  incidence of thrombophilias is also increased in
  women with
• Late fetal loss (abortions)
• Gestational hypertension
• Intrauterine growth restriction
• IUFD

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Recommendations 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)

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Recommendations 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

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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)
• gt 3 moderate risk factors surveillance or UFH or
  prophylactic LMWH dose (1C)

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Postpartum thromboprophylaxis

• All women with class 3 obesity (BMI gt 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

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Summary of protocol for thromboprophylaxis in
women with previous VTE and/or thrombophilia These
women require joint specialist management by
obstetricians and experts in haemostasis and
pregnancy
Very High Risk Previous VTE (/- thrombophilia) on long term warfarin Antithrombin deficiency Antiphospholipid syndrome Antenatal high prophylactic or therapeutic dose LMWH and at least six weeks postnatal warfarin.
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 Antenatal and six weeks postnatal prophylactic LMWH
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) Six weeks postnatal prophylactic LMWH Seven days postnatal LMWH extended to six weeks if family history ve, other risk factors
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Prophylactic doses of UFH and LMWH

• UFH 5000 IU sc bid
• Prophylactic LMWH
• Enoxaparin 40 mg sc q24h,
• Dalteparin 5000 IU sc q24h.
• Antifactor Xa assay 0.2 and 0.6 U/mL 4 hours
  after the injection

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IV 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
• doesnt cross placenta
• not excreted in breast milk

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IV 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 gt 5 months)
• thrombocytopenia (by day 4)
• Cost and compliance

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Low 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

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Low molecular weight heparin

• Disadvantages
• more difficult to reverse
• drug cost higher but no need for hospitalization

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Coumadin

• 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

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Management 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

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Management during peripartum

• 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!

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Take 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

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Take 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

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THANK YOU