Thromboembolic Disease in Pregnancy

Aka: Thromboembolic Disease in Pregnancy, Deep Vein Thrombosis in Pregnancy, Deep Venous Thrombosis During Pregnancy, DVT in Pregnancy, DVT Prophylaxis in Pregnancy, VTE Prophylaxis in Pregnancy, Venous Thromboembolism in Pregnancy, VTE in Pregnancy

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II. Epidemiology

  1. Venous Thrombosis risk: 0.5 to 3 per 1000 pregnancies
    1. Most venous thrombosis events occur in the first 20 weeks of pregnancy
    2. However, highest Incidence rates are in the first 6 weeks postpartum
  2. DVT occurs equally in all trimesters
    1. However Pulmonary Embolism risk increases with each trimester (and especially postpartum)
    2. Postpartum VTE accounts for 50% of pregnancy-related cases
  3. Thromboembolism risk is increased 5 fold in pregnancy
    1. Leading cause of pregnancy related mortality and morbidity in the developed world

III. Pathophysiology

  1. Hypercoagulation in pregnancy
    1. Procoagulants increase
      1. Factor II, Factor VII, Factor X and Fibrin
    2. Anticoagulants decrease
      1. Protein C resistance and decreased Protein S
  2. Venous Stasis increases in pregnancy
    1. Increased intravascular volume distends veins
    2. Inferior vena cava obstructed from Uterus
  3. Vascular damage
    1. Related to vaginal and ceserean delivery

IV. Risk Factors

  1. Primary Thrombophilia (e.g. Factor V Leiden)
    1. Responsible for 50% of Venous Thromboembolism in Pregnancy
  2. Cesarean delivery (Odds Ratio: 13.3)
    1. Deneux-Tharaux (2006) Obstet Gynecol 108:541-8 [PubMed]
  3. Deep Vein Thrombosis history in past
    1. Prior pregnancy induced VTE doubles the risk of future VTE in Pregnancy (4.5% risk)
    2. White (2008) Thromb Haemos 100(2): 246-52 [PubMed]
  4. Mechanical Heart Valve
  5. Atrial Fibrillation
  6. Inflammatory Bowel Disease
  7. Nephrotic Syndrome
  8. Antiphospholipid Syndrome
  9. Prolonged immobilization (e.g. bed rest)
  10. Recent major surgery or Trauma
  11. Age over 35 years
  12. Obesity (BMI >30 kg/m2)
  13. Multiparity over 4 deliveries
  14. Preeclampsia
  15. Current infection

V. Symptoms

  1. Unilateral swelling and discomfort of one leg

VI. Signs

  1. See Deep Vein Thrombosis
  2. See Pulmonary Embolism in Pregnancy
  3. Lower leg circumference >2 cm difference is significant
  4. Superficial phlebitis may occur
  5. Left leg affected in up to 90% of cases
    1. Due to uterine vascular compression resulting in Venous Stasis
  6. Iliofemoral veins involved in 72% of cases (contrast with 9% in nonpregnant patients)
    1. Higher risk of embolization

VII. Imaging

  1. See Pulmonary Embolism in Pregnancy
  2. Venous compression (VCUS) and Venous Doppler Ultrasound for DVT evaluation
    1. Perform late Pregnancy Testing in lateral decubitus position
    2. Proximal DVT is much more common in pregnancy (only 9% are distal DVTs)
      1. Iliofemoral DVT accounts for 72% of pregnancy-related DVTs
    3. Left leg DVT is more common (85%) than right (55%) in pregnancy
      1. Gravid Uterus puts more pressure on left pelvic veins

VIII. Evaluation: Suspected DVT

  1. See Pulmonary Embolism in Pregnancy
  2. Most pregnant patients with Pulmonary Embolism also have a DVT
  3. Low DVT suspicion
    1. Consider D-Dimer: DVT excluded if negative
    2. Venous Compression Ultrasound (VCUS)
      1. Positive: Start Anticoagulation for DVT
      2. Negative: DVT excluded
  4. High DVT suspicion
    1. Start Anticoagulation therapy regardless of Venous Doppler Ultrasound results
    2. Venous Compression Ultrasound (VCUS)
      1. Positive: Continue Anticoagulation per protocol
      2. Negative: Recheck Venous Compression Ultrasound in 5-7 days
        1. Alternatives: Venography (with abdominal shield) or MRV in 1 week
        2. Continue Anticoagulation until repeat testing

IX. Labs: Thrombophilia evaluation

  1. See Thrombophilia
  2. Focus areas in pregnancy
    1. Antiphospholipid Antibody Syndrome
    2. Factor V Leiden
  3. Precautions
    1. Protein C and Protein S may be unreliable in pregnancy (artificially low)
    2. Antithrombin levels may be artificially decreased in pregnancy

X. Management

  1. See Pulmonary Embolism in Pregnancy
  2. See Anticoagulation in Thromboembolism
  3. Low Molecular Weight Heparin
    1. Enoxaparin (Lovenox) 1 mg/kg SC every 12 hours OR 1.5 mg/kg once daily
    2. Preferred option over Unfractionated Heparin
  4. Alternative Anticoagulants in pregnancy
    1. Dalteparin 100 IU/kg twice daily OR 200 IU/kg once daily
    2. Tinzaparin 175 units/kg daily
  5. Avoid other Anticoagulants until after pregnancy
    1. Avoid Warfarin until postpartum
      1. Contraindicated in pregnancy due to Teratogenicity
    2. Avoid Direct Thrombin Inhibitors (e.g. Dabigatran) and Factor Xa Inhibitors (e.g. Rivaroxaban)
      1. Contraindicated in pregnancy and Lactation as no safety data exists
  6. Duration
    1. First Venous Thromboembolism: At least 3 months (including at least 6 weeks postpartum)
      1. May switch to Warfarin in the Postpartum Period (but not in pregnancy)
    2. Recurrent Venous Thromboembolism or Thrombophilia: Long-term Anticoagulation
    3. Some protocols step-down dosing of LMWH after initial treatment (consult with hematology, MFM)
      1. Enoxaparin (Lovenox) 1 mg/kg SC every 12 hours for at least 3 months after Venous Thromboembolism
      2. Decrease dose to intermediate Enoxaparin 40 mg twice daily or prophylactic Enoxaparin 40 mg daily
      3. Continue Anticoagulation for at least 6 weeks postpartum
  7. Peripartum Anticoagulation management
    1. Spontaneous labor: Stop Anticoagulation at onset of labor
    2. Elective induction, planned Cesarean Section: Stop Anticoagulation 24 hours before delivery
    3. Mechanical Heart Valves:
      1. Switch to Unfractionated Heparin at onset of labor
      2. Stop Unfractionated Heparin 4-6 hours before anticipated delivery
    4. Regional Anesthesia (Epidural and intrathecal Anesthesia)
      1. Avoid Regional Anesthesia within 24 hours of last LMWH when twice daily dosing
      2. Avoid Regional Anesthesia within 12 hours of last LMWH when daily dosing (prophylaxis)
    5. Restarting Anticoagulation
      1. Restart 4 hours after delivery and after epidural catheter has been removed

XI. Prevention: DVT Prophylaxis (and other Anticoagulation indications)

  1. Indications
    1. Mechanical Heart Valve
    2. Rheumatic Heart Disease
    3. Atrial Fibrillation
    4. Antithrombin III Deficiency
    5. Antiphospholipid Syndrome
    6. Prior Anticoagulation therapy
    7. Factor V Leiden Defect
    8. Prothrombin G20210A Mutation
    9. Unprovoked Venous Thromboembolism History
    10. Hormonally (e.g. Oral Contraceptive) or Pregnancy Related Venous Thromboembolism History
  2. Protocol: General
    1. Start in pregnancy and continue for 6 weeks postpartum (safe in Lactation)
    2. Do not use Warfarin (contraindicated due to Teratogenicity)
    3. Do not use Direct Oral Anticoagulants such as Eliquis (have not been studied in pregnancy and Lactation)
    4. Do not use Aspirin for DVT Prophylaxis (not effective)
    5. Do not use Compression Stockings for DVT Prophylaxis in Pregnancy (not effective)
    6. No monitoring with anti-Xa level monitoring needed
  3. Protocol: Low Molecular Weight Heparin: Using Enoxaparin (preferred)
    1. Body weight <50 kg (<110 lb): 20 mg SC daily
    2. Body weight 50-90 kg (110-199 lb): 40 mg SC daily
    3. Body weight >90 kg (>199 lb): 40 mg SC every 12 hours
  4. Protocol: Unfractionated Heparin
    1. Low dose prophylaxis
      1. First trimester: 5000 to 7000 Units q12 hours
      2. Second trimester: 7500 to 10,000 Units q12 hours
      3. Third trimester: 10,000 Units q12 hours
        1. Unless aPTT elevated
    2. Adjusted dose prophylaxis to aPTT of 1.5 to 2.5
      1. Dose: 10,000 q8-12 hours
      2. Goal aPTT: 1.5 to 2.5 times normal
  5. References
    1. (2016) Presc Lett 23(12): 69-70

XII. Complications

  1. Pulmonary Embolism in Pregnancy (and postpartum)
    1. Accounts for 10% of maternal deaths in U.S.
    2. Most common in Postpartum Period (Relative Risk 15)
    3. More commonly follows Cesarean Section

XIII. References

  1. (2015) Presc Lett 22(1): 3
  2. (2000) ACOG Practice Bulletin 19:1-10
  3. Bavolek and Herbert in Herbert (2021) EM:Rap 21(2): 4-5
  4. Vaught and Ponce (2018) Crit Dec Emerg Med 32(8): 14-5
  5. Bates (2018) Blood Adv 2(22): 3317-59 [PubMed]
  6. Bates (2004) Chest 126:627S-644S [PubMed]
  7. Dresang (2008) Am Fam Physician 77:1709-16 [PubMed]
  8. Krivak (2007) Obstet Gynecol 109:761-77 [PubMed]
  9. Zotz (2003) Semin Thromb Hemost 29:143-54 [PubMed]

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