Overview
Pregnancy is a hypercoagulable state, with an increases risk of deep venous thrombosis (DVT) and pulmonary embolism (PE). All clotting factors increase (apart from factor XI and XIII) and stasis in lower limb vessels increases due to compression of the iliac veins by the gravid uterus. The most common site of thrombosis in pregnancy is the left ilio-femoral vein due to anatomical compression by the right common iliac artery over the pelvic brim (May-Thurner syndrome)
The incidence of DVT is increased by 5 times in pregnancy. The incidence of DVT is 1 in 1000 and the incidence of PE is 1 in 7000 in pregnancy. DVT is most common in the post-operative period, and is 9 times more common following caesarean delivery than vaginal delivery.
Factors contributing to venous thromboembolism in pregnancy
| Component of Virchow’s triad | Factors |
|---|---|
| Hypercoagulability | Estrogen increases the production of fibrinogen, factor VII, IX and X. There is also resistance to protein C in the 2nd and 3rd trimester and reduced activity of protein S and Antithrombin III. The levels of fibrinolysis inhibitors also increases. |
| Stasis | Compression of the iliac veins by the gravic uterus and hypovolemia due to hyperemesis gravidarum or hemorrhage post-partum. Immobility post-partum may also contribute to stasis |
| Endothelial injury | Endothelial injury from pre-eclampsia, puerperal sepsis, placental abruption and even delivery itself |
Risk factors for thromboembolism in pregnancy
| Category | Risk factors |
|---|---|
| Pre existing risk factors | Maternal age > 35 years, thrombophilia, obesity (> 80 kg), history of thromboembolism, severe varicose veins, smoking, malignancy |
| Pregnancy-related risk factors | Multiple gestation, pre-eclampsia, grand multiparity, caesarean delivery (especially emergency), damage to pelvic veins, sepsis, prolonged bed rest |
| Transient risk factors | Dehydration, hyperemesis, sepsis, long-distance travel |
- Risk factors for Venous Thromboembolism in Pregnancy (In Pregnancy Variable Antenatal FactorS Often Indicate Low Molecular Heparin Prophylaxis)
- Immobility
- Parity ≥ 3
- Varicose veins (gross)
- Age > 35 years
- Family history of VTE
- Smoker
- Obesity
- IVF conception
- Low-risk thrombophilia
- Multiple pregnancies
- Signs and symptoms of deep venous thrombosis
- Symptoms are often unilateral
- Pain
- Swelling
- Tenderness
- Redness
- Leg circumference discrepancy of > 3 cm in the affected leg (measured 10 cm from the ischial tuberosity or 20 cm from the ASIS)
- Symptoms are often unilateral
- Signs and symptoms of pulmonary embolism
- Difficulty in breathing
- Cough
- Hemoptysis
- Chest pain
- Hypoxia
- Tachycardia
- Raised respiratory rate
- Low-grade fever
- Hypotension
- Differentials for DVT
- Cellulitis
- Superficial thrombophlebitis (has a palpable cord)
- Varicose veins
- Lymphedema
- Compartment syndrome
- Ruptured popliteal cyst
- Investigations
- Doppler ultrasound of the lower limb: for DVT. Repeat negative ultrasound on day 3 and 7 in high-risk patients.
- Venography: a more invasive and expensive alternative to doppler ultrasound
- Chest X-ray and EKG: initial investigations for patients with suspected pulmonary embolism
- CT-pulmonary angiogram (CTPA) or Ventilation-perfusion (VQ) scan: for definitve diagnosis. CTPA is preferred if there is an abnormal chest X-ray. It carres a high risk of breast cancer for the mother.
- Ventilation-perfusion (VQ)scan: for definitive diagnosis. Carries a high-risk of childhood cancer for the fetus.
- D-dimer: not useful since pregnancy causes a rise in D-dimer
- aPTT: for accurate heparinization
- Adequate heparinization = aPTT 1.5-2.5
- Supportive treatment
- Adequate hydration
- Limb elevation
- Bed rest
- Analgesia
- Elastic stockings
- Early ambulation post-operative
- Definitive treatment
- IV unfractionated heparin
- (UFH)
- Check for adequate heparinization with aPTT
- Switch to SC LMWH once acute phase is over
- Thrombolysis or surgical embolicteomy for pulmonary embolism
Thromboprophylaxis in Pregnancy
Thromboprophylaxis can be started at 28 weeks if there are at least three risk factors. It can also be started as soon as the first trimester if there are 4 or more risk factors.
Women with increased risk of VTE receive prophylaxis with low molecular weight heparin (LMWH) unless contraindicated. They include enoxaparin, dalteparin and tinzaparin. Mechanical prophylaxis with intermittent pneumatic compressin devices or anti-embolic compression stockings can be used for women with contraindications to LMWH. Prophylaxis is temprarily stopped during labour and delivery and can be started immediately after delivery, provided there was no post-partum hemorrhage or neuraxial anaesthesia.
For high-risk women, prophylaxis is continued for up to 6 weeks postpartum since it takes 6 weeks for clotting factors to return to normal after delivery.
When to start thromboprophylaxis in pregnancy
| Risk factors | When to start thromboprophylaxis |
|---|---|
| ≥ 4 risk factors | Prophylaxis from first trimester |
| > 3 risk factors | Prophylaxis from 28 weeks |
| <3 risk factors | Proper hydration and ambulation. |
- Indications for thromboprophylaxis in pregnancy regardless of risk factors
- History of prior VTE, not due to major surgical event (very high-risk situation)
- History of DVT due to major surgery
- Undergoing prolonged surgery or hospital admission
- High-risk thrombophilia
- Ovarian hyperstimulation syndrome (after IVF): causes a hypercoagulable state due to high-estrogen
- Medical comorbidities such as cancer, heart failure, sickle cell, arthritis or active SLE
Post-natal thromboprophylaxis in pregnancy
| Group | Duration of thromboprophylaxis |
|---|---|
| High-risk | LMWH (enoxaparin) during pregnancy and 6 weeks post-partum |
| Intermediate-risk | LMWH (enoxaparin) during pregnancy at least 10 days postpartum |
| Low-risk | Proper hydration, exercise and ambulation. Prevent trauma, sepsis, anaemia and dehydration. |
- Considerations for thromboprophylaxis during pregnancy
- Switching from LMWH to UFH
- Start with UFH from 0 – 16 weeks
- Switch to LMWH between 16 weeks to 36 weeks (requires little monitoring and has a lower side-effect profile compared to UFH)
- Switch to UFH from 36 week to delivery since UFH has a shorter half-life than LMWH heparin (effect goes away in 12 hours), can be monitored easily with aPTT and protamine sulphate as an antidote is available
- Stopping heparin (due to increased risk of PPH and hematoma during regional anaesthesia)
- 12 hours before delivery for prophylactic dose
- 24 hours before delivery for therapeutic dose
- Restarting heparin (provided no neuraxial anaesthesia, post-partum hemorrhage or other fresh risk factors)
- 4 – 6 hours after vaginal delivery
- 6 – 12 hours after caesarean delivery
- Can switch to oral anticoagulation after delivery using warfarin or a DOAC
- Switching from LMWH to UFH
- Side effects of heparin
- Hemorrhage
- Osteoporosis
- Heparin-induced Thrombocytopenia (HIT)
- Hypotension
- Alopecia
- Allergic reaction
- Pain at the injection site
