Thromboembolic Disease 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
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
   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. DVT evaluation
      1. Perform late Pregnancy Testing in lateral decubitus position
      2. Venous compression Ultrasound (VCUS)
   2. PE evaluation
      1. Spiral CT
         1. Fetal Radiation Exposure: 130 uGy
      2. Ventilation-Perfusion Scan (V/Q Scan)
         1. Fetal Radiation Exposure: 370 uGy
      3. MRI Lung
      4. Pulmonary Angiography
8. Evaluation: Suspected DVT
   1. 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
   2. 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. Evaluation: Suspected Pulmonary Embolism
   1. Low DVT suspicion: Obtain D-Dimer
      1. D-Dimer negative: PE excluded
      2. D-Dimer positive: Go to high suspicion protocol below
   2. Intermediate or High DVT suspicion: Obtain Spiral CT (or V/Q Scan if CT not available)
      1. Spiral CT normal: PE excluded
      2. Spiral CT positive: Anticoagulation per Pulmonary Embolism protocol
      3. Spiral CT indeterminate: Obtain additional testing
         1. Ventilation-Perfusion Scan (V/Q Scan)
         2. Venous compression Ultrasound (VCUS)
         3. MRI Lung
         4. Pulmonary Angiography
10. 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
11. Management
    1. See Anticoagulation in Thromboembolism
    2. Low Molecular Weight Heparin (e.g. Lovenox 1 mg/kg SC every 12 hours)
       1. Preferred option over Unfractionated Heparin
    3. Avoid Warfarin until postpartum (contraindicated in pregnancy)
    4. Duration
       1. First Venous Thromboembolism: 6 months (including at least 6 weeks postpartum)
       2. Recurrent Venous Thromboembolism or Thrombophilia: Long-term Anticoagulation
    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)
12. Prevention: DVT Prophylaxis
    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
       1. 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
       2. Low Molecular Weight Heparin: Using Enoxaparin (Lovenox)
          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
13. Complications
    1. Pulmonary Embolism
       1. Most common in postpartum period (relative risk 15)
       2. More commonly follows cesarean section
14. References
    1. (2000) ACOG Practice Bulletin 19:1-10
    2. Bates (2004) Chest 126:627S-644S
    3. Dresang (2008) Am Fam Physician 77:1709-16
    4. Krivak (2007) Obstet Gynecol 109:761-77
    5. Zotz (2003) Semin Thromb Hemost 29:143-54