- Although CARPA is influenced by infusion rate and formulation stability, the prevailing mechanistic model holds that complement activation is triggered by the nanoparticle form of the iron complex, rather than solely by “free iron” release.
- Modern IV iron agents are colloidal nanoparticles whose surface chemistry, size, and charge can provoke complement binding and activation (via classical, lectin, or alternative pathways).
- Rapid infusion increases the instantaneous nanoparticle exposure to complement proteins, increasing the likelihood of activation before immune regulatory clearance can intervene.
- The composition, molecular weight, charge, and structural integrity of the nanoparticle shell determine how the particle behaves in plasma and how likely it is to trigger complement activation (CARPA) or release labile iron.
- These properties vary between different formulation, this infusion time differs.
- For example, ferric carboxymaltose is very stable and can be indufed over 13-30 min whereas iron sucrose is less stable and is over 1-2 h.
- Loosely bound (labile) iron may amplify downstream inflammatory effects but is not considered the primary initiator of CARPA in current formulations. However, the difference in allowable infusion speeds between IV iron formulations primarily reflects differences in nanoparticle structure and stability, not free iron release.
- Note: Iron dextran is very stable but more immunogenic (dextran allergy risk) so is given over 1-6 h.
Oct
12
2025