What are the risks of using thrombolytics, such as alteplase (tissue plasminogen activator), in a pregnant woman with pulmonary embolism (PE) to the fetus?

Risks of Thrombolytics to a Fetus in Maternal Pulmonary Embolism

Thrombolytics such as alteplase do not cross the placenta and appear to have a relatively favorable safety profile for the fetus when used for life-threatening pulmonary embolism (PE) in pregnant women, though experience is limited and risks must be carefully weighed. 1

Fetal Risks of Thrombolytic Therapy

• Thrombolytic agents like streptokinase and alteplase do not cross the placenta, which significantly reduces direct fetal exposure and potential teratogenic effects 1

• The primary fetal concerns with thrombolytic therapy are indirect and related to placental effects, potentially resulting in:

  • Premature labor
  • Placental abruption
  • Fetal demise 1

• Animal studies in rats and rabbits did not demonstrate teratogenicity with alteplase 1

• In published cases of pregnant women receiving thrombolytics, fetal outcomes appeared not to be affected, with complication rates similar to non-pregnant patients 1, 2

• A systematic review of thrombolysis for massive PE during pregnancy found 88% fetal survival, suggesting relatively good outcomes despite the critical maternal condition 2

Maternal Considerations That Impact Fetal Risk

• The major risk to the fetus comes from maternal bleeding complications, which occur in approximately 8% of pregnant women receiving thrombolytics, usually from the genital tract 1

• Bleeding risk is significantly higher in the postpartum period (58%) compared to antepartum (17.5%), which may indirectly affect fetal outcomes if treatment is needed around delivery 2

• No intracranial hemorrhages were reported in pregnant women receiving thrombolytics for PE in systematic reviews, which is reassuring for maternal safety 3, 2

• Maternal survival with thrombolysis for massive PE during pregnancy is approximately 94%, which is critical for fetal survival 2

Timing Considerations

• The risk-benefit ratio differs significantly based on gestational age and proximity to delivery:

  • First trimester: Minimal placental tissue, lower bleeding risk
  • Third trimester: Larger placental surface, higher bleeding risk
  • Peripartum/immediate postpartum: Highest bleeding risk 3, 2

• Approximately half of severe postpartum PEs occur within 24 hours of delivery, when bleeding risk is highest 2

Treatment Recommendations

• For pregnant women with PE, thrombolysis should generally be reserved for life-threatening hemodynamic instability, as the risk of bleeding outweighs potential benefits in submassive PE with right ventricular dysfunction alone 1

• In the peripartum and early postpartum period, non-fibrinolytic treatments (catheter-directed thrombectomy, surgical embolectomy, or ECMO) may be preferred as first-line treatments due to the particularly high bleeding risk, if such expertise is available 4, 3

• When thrombolysis is necessary for life-threatening PE during pregnancy, alteplase appears to be the most frequently used agent (67% of reported cases), though often at modified dosing regimens 3

• Catheter-directed thrombolysis with lower doses of thrombolytics may be considered to potentially reduce systemic bleeding complications while maintaining efficacy 3, 5

Practical Considerations

• The FDA label for alteplase notes embryocidal effects in rabbits at doses approximately 50 times human exposure, but no maternal or fetal toxicity at 16 times human exposure 6

• The decision to use thrombolytics must balance the life-threatening nature of massive PE against the potential risks of bleeding, with maternal survival being the priority 1

• Close monitoring for signs of placental abruption, preterm labor, or fetal distress is essential following thrombolytic administration 1, 3

• A multidisciplinary approach involving pulmonary embolism response teams and obstetricians is crucial for managing these high-risk situations 4