Is Fresh Frozen Plasma (FFP) used to treat anaphylaxis related to Angiotensin-Converting Enzyme (ACE) inhibitors?

FFP for ACE Inhibitor-Induced Angioedema

Fresh frozen plasma (FFP) has been described as efficacious for ACE inhibitor-induced angioedema in case reports and observational data, but it is not a first-line treatment and should only be considered when bradykinin-targeted therapies (icatibant, C1 inhibitor concentrate) are unavailable and symptoms are severe or life-threatening. 1, 2

Primary Management: Discontinue the ACE Inhibitor

• Immediate and permanent discontinuation of the ACE inhibitor is the cornerstone of therapy for all patients with ACE inhibitor-induced angioedema 1, 2
• All patients require observation in a controlled environment capable of emergency intubation or tracheostomy, as airway compromise can develop rapidly 1, 2
• Consider elective intubation early if any signs of impending airway closure develop (tongue swelling, stridor, voice changes, difficulty swallowing) 2

What Does NOT Work

Standard anaphylaxis treatments—epinephrine, corticosteroids, and antihistamines—are NOT effective for ACE inhibitor-induced angioedema because the mechanism is bradykinin-mediated, not histamine-mediated 1, 2, 3

This is a critical pitfall: ACE inhibitor angioedema is NOT anaphylaxis, despite superficial similarities in presentation 1, 2

Evidence for FFP Use

The evidence supporting FFP for ACE inhibitor-induced angioedema consists of:

• The 2013 AAAAI guidelines state that "efficacy of icatibant and fresh frozen plasma have been described for ACE-I–associated angioedema; however, no controlled studies have been reported" 1
• Case reports demonstrate rapid improvement with FFP administration (2 units IV) in patients with resistant, life-threatening tongue and airway swelling that failed conventional therapy 4, 5
• The proposed mechanism is that FFP contains kininase II (ACE enzyme), which can break down accumulated bradykinin 4

When to Consider FFP

FFP should only be used when:

• Bradykinin-targeted therapies (icatibant 30 mg subcutaneously or C1 inhibitor concentrate) are not readily available 2
• Symptoms are severe or life-threatening (significant tongue swelling, airway compromise, or progression despite observation) 2, 4
• The patient is in a facility capable of managing potential transfusion reactions and airway emergencies 2

FFP Dosing and Administration

• Administer 2 units of FFP intravenously based on case report evidence 4, 5
• Expect improvement within hours if FFP is effective 4
• Monitor closely for transfusion reactions, volume overload, and pathogen transmission risk 1

Important Caveats About FFP

While FFP has been used successfully in ACE inhibitor-induced angioedema, it carries significant risks:

• Transfusion reactions occur in approximately 5% of patients, including rare severe anaphylactic reactions 1
• Risk of volume overload, particularly in patients with cardiac or renal disease 1
• Potential for blood-borne pathogen transmission 1
• No controlled trials exist to definitively establish efficacy 1

Long-Term Management

• Never restart the ACE inhibitor—patients who experience angioedema with one ACE inhibitor will typically react to all others (class effect) 1, 2
• Switching to an angiotensin receptor blocker (ARB) carries a modest recurrence risk of 2-17%, though most patients tolerate ARBs without recurrence 1, 2
• Consider alternative antihypertensive agents (calcium channel blockers, thiazide diuretics) as safer options 1

Clinical Algorithm

1. Immediately discontinue ACE inhibitor 1, 2
2. Assess airway - intubate early if any signs of compromise 2
3. Do NOT give epinephrine, antihistamines, or corticosteroids as primary therapy 1, 2
4. First choice: Icatibant 30 mg SC or C1 inhibitor concentrate if available 2
5. Second choice: FFP 2 units IV if bradykinin-targeted therapies unavailable and symptoms severe 2, 4
6. Observe for 48-72 hours as attacks typically last this duration 3