Distinct in vitro Complement Activation by Various Intravenous Iron Preparations.

Area of Science:

• Immunology
• Nephrology
• Pharmacology

Background:

• Intravenous (IV) iron is crucial for treating anemia in hemodialysis (HD) patients.
• Hypersensitivity reactions are a known risk of IV iron, but their mechanism remains unclear.
• Complement activation-related pseudo allergy (CARPA) is hypothesized as a potential cause.

Purpose of the Study:

• To investigate the complement-activating capacity of five common IV iron preparations.
• To determine if these reactions are linked to CARPA in HD patients.

Main Methods:

• In vitro complement activation assays for three complement pathways.
• Ex vivo testing using whole blood from healthy volunteers and HD patients.
• In vivo complement activation assessment in HD patients for one preparation.

Main Results:

• Iron dextran and ferric carboxymaltose activated complement in vitro (alternative pathway).
• Iron dextran activated complement ex vivo in both healthy and HD patient blood.
• Ferric carboxymaltose and iron sucrose activated complement ex vivo only in HD patient blood.
• Ferumoxytol and iron isomaltoside did not activate complement.

Conclusions:

• Iron dextran and ferric carboxymaltose possess in vitro complement-activating properties.
• Hypersensitivity reactions to these IV iron drugs may be mediated by CARPA.