ABSTRACT
BACKGROUND: Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA). METHODS: First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways. Additionally, the preparations were tested in an ex-vivo model using the whole blood of healthy volunteers and HD patients. Lastly, in-vivo complement activation was tested for one preparation in HD patients. RESULTS: In the in-vitro assays, iron dextran, and ferric carboxymaltose caused complement activation, which was only possible under alternative pathway conditions. Iron sucrose may interact with complement proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron dextran significantly induced complement activation in the blood of healthy volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric carboxymaltose and iron sucrose only caused significant complement activation in the blood of HD patients. No in-vitro or ex-vivo complement activation was found for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose in HD patients did not lead to significant in-vivo complement activation. CONCLUSION: This study provides evidence that iron dextran and ferric carboxymaltose have complement-activating capacities in-vitro, and hypersensitivity reactions to these drugs could be CARPA-mediated.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Complement Activation/drug effects , Hematinics/pharmacology , Iron Compounds/pharmacology , Kidney Failure, Chronic/therapy , Administration, Intravenous , Anemia, Iron-Deficiency/complications , Complement C1q/drug effects , Complement C1q/metabolism , Complement C3d/drug effects , Complement C3d/metabolism , Complement Membrane Attack Complex/drug effects , Complement Membrane Attack Complex/metabolism , Disaccharides/pharmacology , Disaccharides/therapeutic use , Ferric Compounds/pharmacology , Ferric Compounds/therapeutic use , Ferric Oxide, Saccharated , Ferrosoferric Oxide/pharmacology , Ferrosoferric Oxide/therapeutic use , Glucaric Acid/pharmacology , Glucaric Acid/therapeutic use , Hematinics/therapeutic use , Humans , In Vitro Techniques , Iron Compounds/therapeutic use , Iron-Dextran Complex/pharmacology , Iron-Dextran Complex/therapeutic use , Kidney Failure, Chronic/complications , Maltose/analogs & derivatives , Maltose/pharmacology , Maltose/therapeutic use , Mannose-Binding Lectin/drug effects , Mannose-Binding Lectin/metabolism , Properdin/drug effects , Properdin/metabolism , Renal DialysisABSTRACT
Sodium selenite exerts a marked inhibiting effect on the hemolysis induced by complement fixation. The results of rocket immunoelectrophoresis tests for the activated fragments C3d and C4d show that sodium selenite inhibits complement activation through the alternative pathway.
Subject(s)
Complement Activation/drug effects , Complement C4b , Selenium/pharmacology , Complement C3d/drug effects , Complement C4/drug effects , Hemolysis/drug effects , Humans , Peptide Fragments/drug effects , Sodium SeleniteABSTRACT
Four different radiographic contrast media (RCM) were used for i.v. urography in 40 patients, none of whom had complications. No rise in C3d was observed for any of the RCM, indicating that complement was not activated. However, significantly decreased values for CH50 were detected when the non-ionic RCM iopamidol and iohexol were used, and this may be due to interaction between the RCM and the complement molecules. Significantly increased numbers of neutrophils were observed in patients receiving ioxaglate, iohexol and diatrizoate, which may be due to inhibition of granulocyte adherence. No rise in the concentration of elastase and lactoferrin was observed. On the other hand, significantly decreased values of elastase were seen after injection of diatrizoate, which may be due to inhibition of the degranulation process by this media.
Subject(s)
Complement System Proteins/drug effects , Contrast Media/pharmacology , Granulocytes/enzymology , Urography , Complement Activation/drug effects , Complement C3d/drug effects , Complement C3d/metabolism , Complement Hemolytic Activity Assay , Diatrizoate/pharmacology , Granulocytes/drug effects , Humans , Iohexol/pharmacology , Iopamidol/pharmacology , Ioxaglic Acid/pharmacology , Lactoferrin/metabolism , Leukocyte Count/drug effects , Neutrophils/drug effects , Pancreatic Elastase/metabolismABSTRACT
Complement activation is believed to be of importance in the development of complications arising after cardiopulmonary bypass. The effect on complement activation of priming the extracorporeal circuit with crystalloid alone, crystalloid plus albumin, or crystalloid plus the plasma expander polygeline was assessed in 36 patients undergoing coronary artery operations with cardiopulmonary bypass using a bubble oxygenator. Activation of the alternative and common complement pathways was monitored before, during, and after the bypass period by measuring concentrations of factor B and its fragment Ba and C3 and its fragment C3d. Complement activation occurred in all three groups of patients, with no difference between the crystalloid and crystalloid-albumin groups. In contrast, Ba fragment concentrations were persistently and significantly lower during and after bypass in the polygeline group, denoting reduced complement activation. C3d levels also showed a tendency to be lower in this group. Our results indicate that addition of polygeline to the priming solution reduces complement activation. Because complement activation is associated with morbidity after cardiopulmonary bypass, addition of polygeline to the priming solution may offer an inexpensive method of reducing morbidity after cardiopulmonary bypass.