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<b><i>Background:</i></b> 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). <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.【背景】静脉注射（IV）铁剂是血液透析（HD）患者贫血治疗的常用手段。所有静脉铁剂均存在引发超敏反应的风险，但其病理生理机制尚未得到充分阐明。本研究假设，此类超敏反应中有相当比例由补体激活介导，进而表现为被称为补体激活相关假性过敏（complement activation-related pseudo allergy, CARPA）的类过敏性临床表型。 【方法】首先，针对5种临床常用静脉铁剂，采用覆盖补体三条激活通路的功能性补体检测实验，测定其体外补体激活能力。其次，利用健康志愿者与血液透析患者的全血构建离体模型，对上述铁剂开展测试。最后，在血液透析患者体内测试其中一种铁剂的补体激活情况。 【结果】体外实验结果显示，右旋糖酐铁（iron dextran）与羧基麦芽糖铁（ferric carboxymaltose）仅在补体旁路激活通路条件下可引发补体激活。蔗糖铁（iron sucrose）可能与补体蛋白发生相互作用，但未在体外引发补体激活。离体实验中，右旋糖酐铁可显著诱导健康志愿者及血液透析患者全血的补体激活。此外，羧基麦芽糖铁与蔗糖铁仅在血液透析患者的全血中可引发显著补体激活。芬莫昔多（ferumoxytol）与异麦芽糖铁（iron isomaltoside）未在体外或离体实验中检测到补体激活。血液透析患者接受羧基麦芽糖铁静脉铁剂治疗后，未出现显著的体内补体激活。 【结论】本研究证实，右旋糖酐铁与羧基麦芽糖铁具备体外补体激活能力，此类药物引发的超敏反应可能由补体激活相关假性过敏介导。