What is the pathophysiology behind Venous Thromboembolism (VTE) in pregnancy, which affects approximately 1 in 1,000 pregnancies?

Pathophysiology of Venous Thromboembolism in Pregnancy

Pregnancy induces all three components of Virchow's triad—hypercoagulability, venous stasis, and vascular injury—creating a perfect storm for venous thromboembolism (VTE) that affects approximately 1 in 1,000 pregnancies. 1

Hypercoagulability in Pregnancy

• Pregnancy creates a state of hypercoagulability starting from conception, which is an evolutionary mechanism designed to reduce hemorrhage during childbirth or pregnancy loss 1
• This hypercoagulability persists throughout pregnancy and extends beyond 6 weeks postpartum 1
• Specific coagulation changes include:
  • Increased levels of coagulation factors (especially fibrinogen, factor VII, VIII, X) 2
  • Decreased fibrinolysis (reduced ability to break down clots) 2
  • Decreased levels of natural anticoagulants (protein S) 3

Venous Stasis

• Progesterone-mediated venous dilation occurs early in pregnancy 3
• Mechanical compression of the inferior vena cava and pelvic veins by the enlarging uterus reduces venous return from the lower extremities 2
• Decreased mobility, especially in late pregnancy and immediately postpartum 4
• These factors lead to blood pooling in the lower extremities, increasing the risk of deep vein thrombosis 3

Vascular Injury

• Endothelial damage during delivery (both vaginal and cesarean) 1
• Vascular trauma during surgical interventions (cesarean delivery, surgical management of miscarriage or ectopic pregnancy) 1
• Inflammatory changes to vessel walls during pregnancy 3

Timing and Distribution of VTE Risk

• VTE risk exists from the first trimester and continues through the postpartum period 1
• Incidence of VTE among pregnant women is 199.7 per 100,000 women-years, four times higher than in non-pregnant women of similar age 1
• Postpartum period carries the highest risk—five times higher than the antepartum period (511.2 vs 95.8 per 100,000 women-years) 1
• Approximately 80% of pregnancy-related VTEs are deep vein thrombosis, with the remaining 20% being pulmonary emboli 1

Clinical Manifestations

• Deep vein thrombosis is the most common VTE during pregnancy 4
• Pulmonary embolism contributes to higher morbidity and mortality 4
• Rare but serious manifestations include splanchnic vein thrombosis and cerebral vein thrombosis 1

Mortality Impact

• VTE is a leading cause of maternal mortality worldwide 1
• In developed countries, approximately 15% of maternal deaths result from pulmonary embolism 1
• Mortality rates vary by region:
  • United Kingdom: 1 death per 100,000 births (4% of maternal deaths) 1
  • United States: 9.2% of maternal deaths 1
  • Australia: 8.5% of maternal deaths 1
  • South Africa: 5 deaths per 100,000 births 1

Risk Factors Beyond Pregnancy

• Previous history of VTE 1
• Inherited thrombophilias (high-risk or low-risk) 1
• Advanced maternal age 2
• Obesity 4
• Multiple gestations 2
• Cesarean delivery (especially emergency cesarean) 5
• Postpartum infection 4
• Immobility combined with other risk factors 4

Clinical Implications

• Early risk assessment is essential for all pregnant women 5
• Prophylaxis with low-molecular-weight heparin (LMWH) is recommended for high-risk women 1
• Sequential compression devices are recommended for women undergoing cesarean delivery 1
• Risk assessment should be repeated throughout pregnancy and postpartum as new risk factors may develop 5

Understanding the pathophysiology of pregnancy-associated VTE is crucial for implementing appropriate preventive strategies and reducing maternal morbidity and mortality.