What are the risk factors for and how to prevent Venous Thromboembolism (VTE) in pregnant women?

Risk Factors and Prevention of Venous Thromboembolism (VTE) in Pregnant Women

Pregnant women should receive risk-stratified VTE prophylaxis based on personal history of VTE, thrombophilia status, and additional risk factors, with low-molecular-weight heparin (LMWH) as the preferred agent for those requiring pharmacological prophylaxis. 1

Risk Factors for VTE in Pregnancy

Physiological Risk Factors

• Pregnancy itself creates a hypercoagulable state with most coagulation factors increasing during pregnancy 2
• Hemodilution effect: 40-50% increase in plasma volume compared to only 20-30% increase in red cell mass 2

Major Risk Factors

• Previous history of VTE (especially unprovoked or pregnancy/estrogen-related) 1
• Thrombophilia:
  • High-risk: Homozygous Factor V Leiden, Prothrombin gene mutation, Antithrombin deficiency
  • Moderate-risk: Protein C deficiency, Protein S deficiency, heterozygous Factor V Leiden
  • Compound heterozygosity (multiple thrombophilias) 1
• Family history of VTE in first-degree relative before age 50 1

Additional Risk Factors

• Obesity (BMI ≥30 kg/m²) 1
• Smoking (>10 cigarettes per day) 1
• Cesarean section (especially emergency) 1
• Preeclampsia 1
• Intrauterine growth restriction 1
• Placenta previa 1
• Peripartum/postpartum hemorrhage >1L 1
• Preterm delivery 1
• Stillbirth 1
• Maternal comorbidities:
  • Cardiac disease
  • Systemic lupus erythematosus
  • Sickle cell disease
  • Inflammatory diseases
  • Varicose veins
  • Gestational diabetes 1
• Prolonged immobility 1
• Severe ovarian hyperstimulation syndrome 1

Prevention Strategies

Risk Assessment

1. Low Risk (no personal/family history of VTE, no thrombophilia):

   • Early mobilization
   • No pharmacological prophylaxis needed 1

2. Intermediate Risk (single risk factor or mild thrombophilia without VTE history):

   • Antepartum: Clinical surveillance
   • Postpartum: Consider LMWH prophylaxis for 6 weeks if additional risk factors present 1

3. High Risk (prior VTE, high-risk thrombophilia, or multiple risk factors):

   • Antepartum: Prophylactic or intermediate-dose LMWH
   • Postpartum: Prophylactic LMWH for 6 weeks 1

Specific Recommendations Based on Risk Profile

Prior VTE History

• Single episode associated with transient risk factor (not pregnancy/estrogen-related):

  • Antepartum: Clinical vigilance
  • Postpartum: LMWH prophylaxis for 6 weeks 1

• Unprovoked VTE, pregnancy/estrogen-related VTE, or multiple VTE episodes:

  • Antepartum: Prophylactic or intermediate-dose LMWH
  • Postpartum: LMWH prophylaxis for 6 weeks 1

• Women on long-term anticoagulation:

  • Antepartum: Adjusted-dose LMWH or 75% of therapeutic dose
  • Postpartum: Resume long-term anticoagulants 1

Thrombophilia Without Prior VTE

• Homozygous Factor V Leiden or Prothrombin gene mutation with positive family history:

  • Antepartum: Prophylactic LMWH
  • Postpartum: LMWH or vitamin K antagonists for 6 weeks 1

• Other thrombophilias:

  • Antepartum: Clinical surveillance (regardless of family history)
  • Postpartum: LMWH prophylaxis for 6 weeks if family history of VTE 1

Cesarean Section

• Without additional risk factors:

  • Early mobilization only 1

• With one major or ≥2 minor risk factors:

  • LMWH prophylaxis or mechanical prophylaxis (elastic stockings/intermittent pneumatic compression) if contraindications to anticoagulants 1

• Very high risk (multiple persistent risk factors):

  • Combine LMWH with elastic stockings and/or intermittent pneumatic compression 1

Practical Considerations for LMWH Use

• Timing: Discontinue LMWH at least 24 hours prior to planned delivery or neuraxial anesthesia 1
• Postpartum initiation: 4-6 hours after vaginal delivery or 6-12 hours after cesarean section if no increased bleeding risk 3
• Duration: Continue for 6 weeks postpartum in high-risk women 1
• Dosing: Weight-based dosing is recommended 3

Pitfalls and Caveats

• Despite prophylaxis with low-dose LMWH, high-risk women still have a 5.5% risk of pregnancy-related VTE, suggesting standard prophylactic doses may be insufficient for some high-risk patients 4
• Avoid fondaparinux unless absolutely necessary as it crosses the placenta 5
• For women with mechanical heart valves, specialized anticoagulation regimens are needed 6
• Benzyl alcohol-containing formulations of LMWH should be avoided in neonates due to risk of "gasping syndrome" 7
• Recent evidence suggests that low-dose LMWH is as effective as intermediate-dose for women with prior VTE history, with potentially lower bleeding risk 8

Remember that VTE remains a leading cause of maternal mortality, and proper risk assessment with appropriate prophylaxis can significantly reduce this risk. The benefits of prophylaxis generally outweigh the bleeding risks in high-risk populations.