RESUMEN
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.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Activación de Complemento/efectos de los fármacos , Hematínicos/farmacología , Compuestos de Hierro/farmacología , Fallo Renal Crónico/terapia , Administración Intravenosa , Anemia Ferropénica/complicaciones , Complemento C1q/efectos de los fármacos , Complemento C1q/metabolismo , Complemento C3d/efectos de los fármacos , Complemento C3d/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/efectos de los fármacos , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Disacáridos/farmacología , Disacáridos/uso terapéutico , Compuestos Férricos/farmacología , Compuestos Férricos/uso terapéutico , Sacarato de Óxido Férrico , Óxido Ferrosoférrico/farmacología , Óxido Ferrosoférrico/uso terapéutico , Ácido Glucárico/farmacología , Ácido Glucárico/uso terapéutico , Hematínicos/uso terapéutico , Humanos , Técnicas In Vitro , Compuestos de Hierro/uso terapéutico , Complejo Hierro-Dextran/farmacología , Complejo Hierro-Dextran/uso terapéutico , Fallo Renal Crónico/complicaciones , Maltosa/análogos & derivados , Maltosa/farmacología , Maltosa/uso terapéutico , Lectina de Unión a Manosa/efectos de los fármacos , Lectina de Unión a Manosa/metabolismo , Properdina/efectos de los fármacos , Properdina/metabolismo , Diálisis RenalRESUMEN
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.
Asunto(s)
Activación de Complemento/efectos de los fármacos , Complemento C4b , Selenio/farmacología , Complemento C3d/efectos de los fármacos , Complemento C4/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Fragmentos de Péptidos/efectos de los fármacos , Selenito de SodioRESUMEN
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.
Asunto(s)
Proteínas del Sistema Complemento/efectos de los fármacos , Medios de Contraste/farmacología , Granulocitos/enzimología , Urografía , Activación de Complemento/efectos de los fármacos , Complemento C3d/efectos de los fármacos , Complemento C3d/metabolismo , Ensayo de Actividad Hemolítica de Complemento , Diatrizoato/farmacología , Granulocitos/efectos de los fármacos , Humanos , Yohexol/farmacología , Yopamidol/farmacología , Ácido Yoxáglico/farmacología , Lactoferrina/metabolismo , Recuento de Leucocitos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Elastasa Pancreática/metabolismoRESUMEN
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.