Can Fresh Frozen Plasma (FFP) be used to treat angioedema, specifically hereditary angioedema due to C1 esterase inhibitor deficiency?

Fresh Frozen Plasma for Hereditary Angioedema

Fresh frozen plasma (FFP) can be used as a second-line treatment for hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency when first-line therapies are not available, but it carries risks including possible worsening of symptoms and transfusion reactions.

First-Line Treatments vs. FFP

First-Line Options (Preferred)

• Plasma-derived C1 inhibitor (pdC1INH) is the recommended first-line therapy for both acute attacks and prophylaxis in HAE, especially during pregnancy 1, 2
• Other first-line options for acute attacks include:
  • Icatibant (bradykinin B2 receptor antagonist)
  • Ecallantide (plasma kallikrein inhibitor)
  • Recombinant human C1INH

FFP as Alternative Therapy

• FFP should only be used when first-line treatments are unavailable 1
• FFP contains approximately 1 unit/ml of C1-INH 1
• Typical dosing: 10-15 ml/kg body weight 1

Efficacy of FFP in HAE

• Studies show FFP can be effective in aborting HAE attacks 1, 3
• Response times vary considerably:
  • First improvement: 90 minutes to 12 hours 1
  • Complete resolution: 2-18 hours (median 4 hours) 1
• Some patients require a second treatment, especially if initial dosing is inadequate 1

Risks and Concerns with FFP

Major Risks

1. Potential worsening of symptoms: FFP contains not only C1-INH but also contact system proteins (Factor XII, prekallikrein, high molecular weight kininogen) that can potentially increase bradykinin production before C1-INH takes effect 1

2. Transfusion reactions:

   • Reported in approximately 5% of patients 1
   • Can include severe anaphylactic reactions 1

3. Other risks:

   • Pathogen transmission
   • Volume overload
   • Delayed response compared to first-line therapies

Clinical Application Algorithm

When to Consider FFP

1. First-line treatments (pdC1INH, icatibant, ecallantide) are unavailable
2. Patient has a life-threatening attack requiring immediate intervention
3. Previous positive response to FFP treatment

Administration Protocol

• Dosage: 10-15 ml/kg (typically 2-4 units or 400-560 ml for adults) 1
• Monitoring: Close observation for at least 4-6 hours after administration
• Preparation: Be prepared for potential worsening of symptoms or transfusion reactions
• Follow-up: Consider second dose if inadequate response after 4-6 hours

Special Populations

• Pregnancy: pdC1INH is the preferred treatment during pregnancy, but FFP can be used if pdC1INH is unavailable 1
• Laryngeal attacks: Consider early airway management alongside FFP administration, as response may be delayed 1

Practical Considerations

• In resource-limited settings where first-line treatments are unavailable or prohibitively expensive, FFP remains an important treatment option 1
• Response to FFP is generally slower than with specific HAE medications, requiring longer hospitalization 1
• Always use virally inactivated FFP when available to reduce infection risk 1

Prevention Strategies

For patients relying on FFP due to lack of access to first-line treatments:

• Consider long-term prophylaxis options if attacks are frequent
• Tranexamic acid may be an alternative for prophylaxis when pdC1INH is unavailable 1, 2
• Avoid triggers such as estrogen-containing medications and ACE inhibitors 2