Why is erythropoietin (EPO) use often avoided in pregnancy?

Erythropoietin Use in Pregnancy: Safety Concerns and Considerations

Erythropoietin (EPO) is often avoided in pregnancy primarily due to its significant thrombogenic potential that increases the risk of maternal thromboembolism, which can lead to serious morbidity and mortality. 1

Thrombosis Risk: The Primary Concern

Erythropoietin stimulating agents (ESAs) carry substantial risks that make their use during pregnancy concerning:

• Early trials demonstrated that erythropoietin has thrombogenic potential independent of hemoglobin levels 1
• Meta-analyses have shown a 48-69% increase in relative risk of thrombotic events with ESA use 1
• The absolute risk of venous thromboembolism is 7.5% in patients treated with ESAs compared to 4.9% in control patients 1

This thrombosis risk is particularly concerning in pregnancy, which is already a hypercoagulable state with a 5-10 fold increased risk of venous thromboembolism compared to non-pregnant women.

Additional Safety Concerns

Hypertension and Seizures

• Blood pressure must be controlled before initiating therapy with erythropoietic drugs 1
• Seizures have been reported in patients receiving erythropoietic drugs 1
• Pregnancy already carries risks of hypertensive disorders, making this side effect particularly concerning

Pure Red Cell Aplasia (PRCA)

• Cases of antibody-mediated PRCA have been reported with ESA use 1
• This can lead to severe anemia requiring discontinuation of all erythropoietic drugs 1

Limited Evidence in Pregnancy

Despite these concerns, some research suggests potential benefits in specific circumstances:

• EPO does not appear to cross the placental barrier, suggesting no direct fetal effects 2, 3
• In cases of severe iron deficiency anemia resistant to iron supplementation alone, EPO combined with parenteral iron has shown efficacy 4
• A systematic review found that serial recombinant EPO administration with iron supplementation may be more effective at treating refractory iron deficiency anemia in pregnancy than iron supplementation alone 5

Clinical Approach to Anemia in Pregnancy

For anemia management during pregnancy, guidelines suggest:

1. Optimize hemoglobin values during pregnancy through proper diagnosis and management of anemia 1
2. When iron deficiency is noted, use oral replacement as first-line therapy 1
3. Consider intravenous iron infusions for moderate to severe anemia 1
4. Reserve EPO for specific situations where benefits outweigh risks:
   • Patients with chronic kidney disease who are dialysis-dependent
   • Cases of severe anemia where blood transfusion is refused (e.g., Jehovah's Witnesses)
   • Refractory anemia not responding to iron therapy alone

Monitoring When EPO Is Used

If EPO must be used in pregnancy:

• Ensure adequate iron supplementation 2
• Target a slow and gradual correction of anemia with individually tailored hematocrit goals 2
• Monitor blood pressure closely 1
• Evaluate risk factors for thrombosis before initiating therapy 1
• Consider thromboprophylaxis in patients with additional risk factors for VTE
• Implement close follow-up by an obstetrical-nephrological team 2

In summary, while EPO may have benefits in specific circumstances during pregnancy, its thrombogenic potential, risk of hypertension, and other adverse effects make it a treatment that requires careful consideration of risks versus benefits, with preference given to safer alternatives when possible.