Hematology and Oncology Book

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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
  1. See Also
    1. Deep Vein Thrombosis
    2. Pulmonary Embolism
    3. Pulmonary Embolism in Pregnancy
  2. Epidemiology
    1. Venous Thrombosis risk: 0.5 to 3 per 1000 pregnancies
    2. Thromboembolism risk is increased 5 fold in pregnancy
    3. DVT occurs equally in all trimesters (but PE Risk increases with each trimester and especially postpartum)
  3. 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
  4. 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
    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
  5. Symptoms
    1. Unilateral swelling and discomfort of one leg
  6. Signs
    1. See Deep Vein Thrombosis
    2. Lower leg circumference >2 cm difference is significant
    3. Superficial phlebitis may occur
    4. Left leg affected in up to 90% of cases
    5. Iliofemoral veins involved in 72% of cases (contrast with 9% in nonpregnant patients)
      1. Higher risk of embolization
  7. Imaging
    1. See Pulmonary Embolism in Pregnancy
    2. DVT evaluation
      1. Perform late Pregnancy Testing in lateral decubitus position
      2. Venous Compression Ultrasound (VCUS)
  8. Evaluation: Suspected DVT
    1. See Pulmonary Embolism in Pregnancy
    2. 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
    3. High DVT suspicion
      1. Start Anticoagulation therapy regardless of VCUS
      2. Venous Compression Ultrasound (VCUS)
        1. Positive: Continue Anticoagulation per protocol
        2. Negative: Recheck VCUS or obtain venography (with abdominal shield) in 1 week
          1. Continue Anticoagulation until repeat testing
  9. 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
  10. Management
    1. See Anticoagulation in Thromboembolism
    2. Low Molecular Weight Heparin
      1. Enoxaparin (Lovenox) 1 mg/kg SC every 12 hours
      2. Preferred option over Unfractionated Heparin
    3. 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
    4. Duration
      1. First Venous Thromboembolism: 6 months (including at least 6 weeks postpartum)
      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
    5. 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)
  11. 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
    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
  12. 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
  13. References
    1. (2015) Presc Lett 22(1): 3
    2. (2000) ACOG Practice Bulletin 19:1-10
    3. Bates (2004) Chest 126:627S-644S [PubMed]
    4. Dresang (2008) Am Fam Physician 77:1709-16 [PubMed]
    5. Krivak (2007) Obstet Gynecol 109:761-77 [PubMed]
    6. Zotz (2003) Semin Thromb Hemost 29:143-54 [PubMed]

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