Venous Thromboembolism and Thromboprophylaxis in pregnancy 

Overview

Pregnancy is a hypercoagulable state which increases the risk of venous thromboembolism. All clotting factors (apart from XI and XIII) are increased and stasis increases d/t compression of the iliac veins by the gravid uterus.

The incidence of DVT is 5x more in pregnancy. The incidence of DVT is 1 in 1000 and the incidence of PE is 1 in 7000.

  • Factors causing hypercoagulability
    • Estrogen increases the production of all clotting factors (apart from FXI and FXIII)
  • Factors favoring stasis
    • Compression of the iliac veins by the gravid uterus
    • Hypovolemia due to hyperemesis gravidarum or post-partum hemorrhage
  • Factors causing endothelial injury
    • Delivery itself
    • Pre-eclampsia
    • Severe puerperal infection
    • Placental abruption
  • What is the common site of thrombosis in pregnancy
    • The Left Ilio-femoral veins
    • Caeseren vs vaginal delivery
    • Instrumental vaginal delivery
    • Puerperium (at least 6 weeks for clotting factors to return to normal) → important to ambulate, elastic compression stocking
  • In Pregnancy Variable Antenatal FactorSOften Indicate Low Molecular Heparin Prophylaxis
    • Immobility
    • Parity ≥ 3
    • Varicose veins (gross)
    • Age > 35
    • Family h/o VTE
    • Smoker
    • Obesity
    • IVF conception
    • Low-risk thrombophilia
    • Multiple pregnancies
    • HTN/Pre-eclampsia
      • 4 : 1st trimester
      • 3+ > 28 weeks
      • < 3:mobilization
  • Who needs thromboprophylaxis in pregnancy? (Consider Medicine SHOT)
    • Hx of prior VTE, not d/t major surgical event (very high-risk situation
    • Hx of DVT d/t major surgery
    • Undergoing prolonged surgery
    • High-risk thrombophilia
    • Ovarian hyperstimulation syndrome (after IVF
    • Medical comorbidities (Cancer, Heart failure, Sickle cell, Active SLE)
  • High-risk thromboprophylaxis in pregnancy
    • LMWH (Enoxaparin) during pregnancy and 6 weeks post-partum
  • Intermediate-risk thromboprophylaxis in pregnancy
    • Consider for antenatal prophylaxis with LMWH (Enoxaparin) and 7 days postpartum
  • Low-risk thromboprophylaxis in pregnancy
    • Exercise
    • Ambulation
    • Prevent trauma, sepsis, anaemia, and dehydration.
  • Unfractionated heparin
    • More side effects (bleeding HIT, Osteoporosis)
  • LMWH (Enoxaparin, Dalteparin)
    • Better bioavailability
    • Less frequent dosing
    • Fewer side effects
    • Can use
  • When to stop thromboprophylaxis
    • During labour and delivery
      • Increases risk of PPH
      • Regional anaesthesia technique can cause hematoma (epidural for C/S or repair)
  • When should the woman be switched to UFH from LMWH
    • Last month of pregnancy
      • UFH has shorter t1/2 (stop injection and effect goes away in 12 hours, monitoring effects with aPTT is easier, and Protamine sulphate antidote is available)
  • What should you do if the woman is on LMWH and you need to schedule Elective CS and Induction of labour?
    • Stop LMWH 24 hours prior
  • What is enough time to stop heparin before regional anaesthesia?
    • Prophylactic dose LMWH > 12 hours passed
    • Therapeutic dose LMWH > 24 hours passed
  • How soon can Heparin be started after delivery? (if no regional anaesthesia, PPH, or other fresh risk factors)
    • Soon enough but not before 4 hours post-delivery
    • Reasonable time-frame
      • 12 hours post SVD
      • 24 hours post C/S

VTE in Pregnancy

Do not give warfarin to pregnant women due to its teratogenic potential. It is however safe in breastfeeding women. LMWH is indicated for patients with high-risk inherited thrombophilia, patients with antiphospholipid syndrome, and patients with any thrombophilia and a History of DVT.

DVT occurs in 0.5-2/1000 pregnancies. Common in the left more than the right. Common in the post-op period in C/S (9x greater than SVD)

Wells criteria for DVT

0 = low risk (< 10% chance)

1-2 = intermediate risk (25% chance)

≥ 3 = high-risk (50% chance)

CategoryCriteriaScore
HistoryActive cancer+1
Previously documented DVT+1
ImmobilizationParalysis, paresis, or recent immobilization of lower extremity+1
Recently bedridden for ≥ 3 days or major surgery within the past 12 weeks under anaesthesia+1
Clinical featuresTenderness along the deep venous system+1
Calf swelling ≥ 3 cm compared to the contralateral leg+1
Pitting oedema confined to the symptomatic leg+1
Distended colateral superficial veins (non-varicose)+1
DifferentialAlternative diagnosis is as likely or more likely than DVT-2
  • Risk factors for VTE
    • Inherited or acquired Thrombophilia
    • Previous VTE
    • First-degree relative with VTE
    • Recent surgery
    • Age > 35 years
    • High parity
    • Obesity
    • Smoking
    • Immobilization
    • Active cancer
  • Signs and symptoms
    • Pain
    • Swelling
    • Tenderness
    • Redness
    • Leg circumference > 2cm in the affected leg (measured 10 cm from the ischial tuberosity or 20 cm from the ASIS)
    • Difficulty in breathing
    • Hemoptysis
    Homan sign is no longer used since it can dislodge the thrombus
  • Differentials
    • Cellulitis
    • Superficial thrombophlebitis (has a palpable cord)
    • Varicose veins
    • Lymphedema
    • Compartment syndrome
    • Ruptured popliteal cyst
  • Investigations
    • Doppler US
    • Venography: invasive and expensive
    • Impedance plethysmography
    • D-dimer
    • aPTT: for accurate heparinization
      • Adequate heparinization = 1.5-2.5
  • Supportive Treatment
    • Limb elevation
    • Bed rest
    • Analgesia
    • Elastic stockings
    • Early ambulation post-op
  • Active phase Treatment (warm swollen limb)
    • Analgesia
    • IV Heparin 100 IU/kg the loading → 15-25 UI/kg maintenance infusion (max loading 5000 IU)
      • Does not cross the placenta. Easily reversed with Protamine sulfate.
      • Check for adequate heparinization with aPTT
    • Switch to SC LMWH once acute phase is over
  • Antepartum Treatment
    • SC LMWH (Clexane, Enoxaparin) 40mg OD between 16 – 36 weeks (requires no monitoring, lower side-effects)
    • Heparin 0-16 weeks and 36 weeks to delivery
    • Daily Aspirin in conjunction with LMWH
  • Intrapartum Treatment
    • Anticoagulation should be discontinued 24 hours at the onset of labour (to prevent PPH)
  • Post-partum Treatment
    • Restart aanticoagulation4-6 hrs after VD and 6-12 hrs after C-section (the post-partum period is the highest risk for DVT)
    • Continue post-partum anticoagulation in women with thrombophilia after C-section
  • Side effects of heparin
    • Hemorrhage
    • Osteoporosis
    • Thrombocytopenia
    • Hypotension
    • Alopecia
    • Allergic reaction
    • Pain at the injection site

Thrombophilia in Pregnancy

Pregnancy is a hypercoagulable state. Thrombophilias may be genetic or acquired. Many patients are asymptomatic and manifest symptoms for the first time during pregnancy. The most common manifestation of thrombophilia in pregnancy is maternal DVT and PE. Can also have TIA, Stroke, superficial thrombophlebitis, and fetal loss. Maternal risk is high. Unique risks to the fetus have not been consistently demonstrated. Screening is not appropriate on the grounds of recurrent fetal loss, placental abruption, FGR, or pre-eclampsia

Factor V Leiden mutation: MCC of thrombophilias

Antiphospholipid syndrome (APS): MCC of acquired thrombophilia. Lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and ant-beta2-glycoprotein antibodies increase the risk of thrombosis and cause increased vascular tone. Probably d/t a “second-hit” mechanism. Associated with SLE. Pts can develop DVT, Thrombocytopenia, Livedo reticularis, stroke, superficial thrombophlebitis, and fetal loss.

  • Which women should be screened for inherited thrombophilia?
    • Personal Hx of DVT/VTE
    • Family Hx of DVT/VTE in a first-degree relative (especially if < 50 years old)
  • Why is pregnancy a hypercoagulable state
    • Resistance to protein C in the 2nd and 3rd trimester
    • Protein S activity decreases
    • Fibrinogen fII, fVII, fVIII, and fX levels increase
    • Levels of fibrinolytic inhibitors increase
  • High risk inherited thrombophilias
    • Factor V Leiden mutation, homozygous
    • Prothrombin G20210A mutation, homozygous
    • Antithrombin III deficiency
  • Low risk inherited thrombophilias
    • Factor V Leiden mutation, heterozygous
    • Prothrombin G20210A mutation, heterozygous
    • Protein S deficiency
    • Protein C deficiency
  • Acquired thrombophilias
    • Antiphospholipid antibody syndrome (can be associated with SLE)
      • Causes recurrent pregnancy loss (antibodies target phospholipids in syncytiotrophoblasts, platelets etc)
      • Causes arterial/venous thrombosis
      • Early onset PET
      • Early onset IUGR
      • Stillbirth
  • Indications for screening in thrombophilia
    • History of idiopathic or recurrent VTE
    • FHx of thrombophilia (primary levels
  • Investigations
    • Factor V Leiden mutation
    • Prothrombin G20210A mutation (PGM)
    • Antiphospholipid syndrome
    • Deficiency of protein C, protein S, and antithrombin III
    • Hyperhomocysteinemia