Venous Thromboembolism in Pregnancy

Introduction & Pathophysiology

• VTE is a leading cause of maternal morbidity and mortality in developed countries, accounting for approximately 9.3% of maternal deaths in the United States.¹
• The incidence of VTE is thought to be 1-2 per 1,000 pregnancies; however, the risk is not constant throughout the antepartum, intrapartum, and postpartum periods.
  • More than half of VTEs that occur during pregnancy occur during the first trimester.
  • Overall, the risk is highest in the postpartum period, specifically the first 6 weeks after delivery.²
• The etiology of VTE in pregnancy is best understood in the context of Virchow’s Triad: hypercoagulability, venous stasis, and endothelial dysfunction.

• Hypercoagulability during pregnancy is characterized by increased platelet production and turnover, decreased fibrinolytic activity, and an increase in most coagulation factors, as outlined in Table 1.
• The exact molecular mechanisms of these changes are not well understood, but endogenous increases in oxytocin and placental expression of plasminogen activator inhibitor-2 are thought to contribute to hypercoagulability.³
• Venous stasis can occur from:
  • Anatomic compression of the inferior vena cava, iliac veins, and other pelvic veins by the gravid uterus.
  • Physiologically reduced systemic vascular resistance leading to venous pooling.
• Endothelial dysfunction occurs with the physiologic changes that mediate fluid shifts and angiogenesis during pregnancy and microvascular trauma during vaginal and cesarean births.
  • The risk of endothelial damage is increased in deliveries complicated by factors such as postpartum hemorrhage and infection.⁴

Clinical Presentation & Diagnosis

Presentation

• The diagnosis of VTE during pregnancy is difficult, as typical signs and symptoms of DVT and PE often overlap with the normal physiologic changes of pregnancy.
  • Lower extremity edema
  • Leg pain
  • Pelvic pain
  • Dyspnea
  • Tachypnea
  • Tachycardia
• The most common form of VTE in pregnancy is DVT, which is more likely to be proximal (iliofemoral).
  • Up to 85% of DVTs occur in the left leg due to compression of the left common iliac vein by the gravid uterus.²
• Development of a PE in pregnant individuals carries a significant risk of morbidity and mortality, but up to one-third of PEs may be asymptomatic.⁵

Diagnosis

• Due to the above challenges, a high index of suspicion is required, especially in women with risk factors such as a history of prior VTE.
• Two scoring systems, the modified Wells Score and YEARS score, have shown efficacy in risk-stratifying patients for VTE in pregnancy.
  • The modified Wells Score has shown a 100% negative predictive value for PE in pregnant patients with a score of less than 6.
• D-dimer testing alone is unlikely to provide clinical benefit, but it can increase the sensitivity and specificity of these scoring systems.
• The first-line imaging modality for suspected DVT is compression ultrasonography, with a negative predictive value approaching 99% in most cases.
  • If clinical suspicion remains high despite a negative test, serial ultrasound imaging can be performed as recommended by the American Society of Hematology.⁶
• For patients with suspected PE, the first-line imaging modality is usually CT angiography.
  • Recent literature suggests CT angiography and V/Q scan have comparable efficacy and safety profiles in pregnancy, in addition to IV contrast not being associated with any deleterious effects on the fetus.⁷
  • Both diagnostic modalities are supported by both the American Heart Association and the American Society of Hematology.^5,6
• Imaging for the diagnosis of suspected PE should not be delayed due to pregnancy status.

Peripartum & Inpatient Management

• The management of VTE in pregnancy is complex and should be a multidisciplinary approach that evaluates relevant comorbidities and patient risk factors.
• According to the American Heart Association and the American Society of Hematology, the preferred anticoagulant for both treatment and prophylaxis in pregnancy is low-molecular-weight heparin (LMWH).
  • LMWH carries a lower risk of complications compared to unfractionated heparin (UFH) and does not cross the placenta.^5,6
• Anticoagulation should be continued through the postpartum period for a minimum of 6 weeks and for a total of at least 3 months.
• When prophylaxis or treatment with LMWH is indicated, careful planning of cessation of therapy for the peripartum period is required.
  • For patients who have planned delivery (either induction of labor or scheduled cesarean), patients on twice-daily dosing should hold LMWH 24 hours before the planned procedure, and those on once-daily dosing should take a half-dose the day before their procedure.
  • For unplanned deliveries, bridging with UFH may be indicated based on the clinical scenario, although this practice is not universal.
• Appropriate timing of anticoagulation cessation is of utmost importance in forming an anesthetic plan for delivery to reduce the risk of spinal or epidural hematoma.
  • The American Society of Regional Anesthesia recommends holding LMWH for a minimum of 12 hours for patients on a prophylactic dose, and a minimum of 24 hours for patients on a therapeutic dose before any neuraxial procedure.⁸
  • After catheter removal, prophylactic anticoagulation can be resumed after 4 hours, while therapeutic anticoagulation should be held for 24 hours if a low bleeding risk procedure and 48-72 hours after a high bleeding risk procedure (i.e., cesarean with significant postpartum hemorrhage).⁸