Ingen diastitel

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Maja Jørgensen Trombosecentret Amtssygehuset i
Gentofte Københavns Universitet
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MJ April 2006
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Pregnancy induced risk factors for
thromboembolism

• Changes of hemostasis
• Increased levels of Factors I,V,VII,VIII,
• IX,X,XII and von Willebrand factor
• Decreased levels of Protein S
• Impaired Fibrinolysis
• High venous pressure
• Increased diameter of major leg veins
• Reduction in venous blood flow

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Greer 1996, Lindhagen 1986, Macklon 1997
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Thromboembolic disease in pregnancy
Arterial thromboembolism
Venous thromboembolism
Adverse pregnancy outcomes reflecting thrombotic
events
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Thromboembolism in pregnancy

• The goal of anticoagulation
• to prevent and treat maternal thrombosis
• to improve the outcome of pregnancy

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Venous thromboembolism (VTE) in pregnancy

• Incidence of VTE is 1 2 / 1000
• At least 6 times greater than in
• age-matched non-pregnant women
• VTE is still the most common cause
• of maternel morbidity and mortality

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Eldor 2002, Greer 2003, James 2004, Robertson
2005.
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VTE in pregnancy

• High frequency of left iliofemoral DVT
• High frequency of postthrombotic deep
• venous insufficiency (60 - 80)

• Lindhagen et al 1986, Bergqvist et al 1992

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Incidence of fatal PE in pregnancy
Data from Confidential Enquiries into Maternal
Deaths, UK.
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Incidence of postnatal venous thromboembolism
(VTE)
Data from Confidential Enquiries into Maternel
Deaths, UK.
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Onset of DVT during pregnancy
Bergqvist 1983, Hull 1990, Ginsberg 1992, Ray
1999, James 2005.
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Incidence of venous thromboembolism (VTE) in
women with thrombophilia
Samama et al Br J Haematol 2003
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Incidence of VTE during pregnancy in women with a
single previous VTE
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Risk factors of VTE in pregnancy

• Previous venous thromboembolism
• Thrombophilia
• Family history of venous thromboembolism
• Caesarean section (especially emergency)
• Age gt35 years
• Obesity (BMI gt 30)
• Immobilisation
• Gross varicose veins
• Inflammation
• Severe ovarian hyperstimulation syndrome

McColl et al 1997, Greer 2006
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Haemostatic risk factors of VTE and
complications in pregnancy

• Antithrombin deficiency
• Protein S deficiency
• Protein C deficiency
• Factor V Leiden mutation
• Prothrombin mutation
• Hyperhomocysteinemia
• Antiphospholipid antibodies
• Lupus (RVV, APTT)
• ACA

Robertson et al 2005
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Thrombophilias are associated with different
risks of VTE

• Dependant on
• kind of thrombophilia
• previous thromboembolism
• presence of combined risk factors

• Incidence of VTE in pregnancy
• All 0,10,2
• In thrombophilia 5 30
• After previous VTE 5 30

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Thrombophilias are associated with different
risks of VTE
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Antithrombotic therapy in pregnancy
Warfarin

• Embryopathy
• Chondrodysplasia punctata
• Midface hypoplasia
• Short proximal limbs
• Short phalanges
• Scoliosis

• Fetal cerebral haemorrhage and maternal
  haemorrhage
• Increased risk of low IQ neurological
  dysfunction
• (RR 7.6 for 2 or more defects)
• Wesseling et al 2001

Photo Wellesley et al (1998)BJOG, 105, 805
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Low Molecular Weight Heparins are the agents of
choice in pregnancy

• Does not cross the placenta
• No risk of teratogenesis
• No risk of fetal haemorrhage
• Good bioavailability
• Good pharmacokinetics
• Low risk of allergic reaction
• Low or no risk of osteoporosis
• Low or no risk of HIT

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Are LMWHs safe and efficient in pregnant women ?
No larger randomized controlled studies
Systematic review Greer et al. Blood 2005

• 64 studies reporting 2777 pregnant women treated
  with LMWHs
• But mostly small retrospective studies and
  different inclusion criteria
• 94,7 live births
• 1,4 thrombosis
• 2 significant bleeding
• 0,04 osteoporotic fractures
• No HIT

LMWHs seem to be safe during pregnancy
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Prevention of VTE in pregnancy- A prospective
one center study
M. Jørgensen Thrombosis Centre KAS Gentofte

• 380 pregnancies in 319 women at increased risk of
  VTE treated with Tinzaparin
• 62 acute VTE, 227 with previous VTE and 91 with
  increased risk of TE and no VTE.
• Results
• 99 successful pregnancies resulting in live
  births
• 1.1 venous thromboembolism
• 0.8 miscarriages
• No stillbirth, no serious LMH induced maternal
  haemorrhages, no neonatal haemorrhages

Conclusion The use of tinzaparin in pregnant
women in daily doses up to 200 IU/kg bodyweight
is effective and safe in the treatment and
prophylaxis of venous thrombo-embolism.
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Risk assessment according to kind of thrombophilia
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Treatment regimen according to risk assessment

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Treatment of acute VTE during pregnancy
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Treatment regimen in Antiphospholipid
syndromeand in arterial thromboembolic disease

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Thromboprophylaxis of pregnant women on long-time
anticoagulation

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Treatment of prosthetic heart valves during
pregnancy

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Low Molecular Weight Heparins
Do we need to weight-adjust doses during
pregnancy? Depends on the LMWH used. Once or
twice daily injections? Depends on the LMWH
used. Injections twice daily in high risk
patients. Is monitoring necessary? Only in high
risk females. Is bone density reduced by
LMWH? No.
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• Identification of women at risk of thrombosis
• Individualized risk assessment for each patient
  during pregnancy and delivery
• Anticoagulation treatment according to risk
  assessment using LMWH
• (usually one daily dosing adjusted doses in high
  risk females)
• Graduated compression stockings

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