HYPOPHOSPHATAEMIA FOLLOWING FERRIC CARBOXYMALTOSE INFUSION

Intravenous iron therapy is used to treat iron deficiency anaemia when oral iron preparations are not tolerated, ineffective or contraindicated. Ferric carboxymaltose (FCM) (Ferinject, Vifor Pharma Pty Ltd Australia) is an intravenous iron preparation approved for use in children over 14 years of age with a favourable reported safety profile, tolerability and efficacy and is used in paediatric centres, including in children below 14 years.^{1, 2}

Transient hypophosphataemia has been reported post-iron infusion due to increased fibroblast growth factor-23 driving reduced tubular phosphate reabsorption and lasts for weeks to months.³ We have observed that frequent prescribers of FCM are not aware of hypophosphataemia as a possible adverse effect, however, this is an important differential to consider for severe refractory or symptomatic hypophosphataemia in patients following iron infusion.

We report a 17-year-old female with Crohn's disease who presented with partial small bowel obstruction, bradycardia, hypotension and fatigue 12 days following FCM infusion. Bloods revealed severe hypophosphataemia (0.30 mmol/L). Intravenous phosphate correction was prescribed and she was managed conservatively. Minimal serum phosphate increment was noticed the following day and she required daily intravenous phosphate corrections for the next 5 days. On day 6 of admission, her serum phosphate remained low (0.59 mmol/L). Paired urine and serum samples showed elevated fractional excretion of phosphate (38%), confirming renal phosphate wasting. She was discharged on oral phosphate supplements and her serum phosphate normalised on day 22 post-FCM.

Current evidence on the clinical significance of iron-induced acute hypophosphataemia is conflicting. The vast majority of affected individuals in adult studies were asymptomatic; however, case reports describe otherwise unexplained fatigue, lethargy and muscle weakness.³

Chronic hypophosphataemia is documented in adults following repeated FCM doses, with case reports of osteomalacia and bone deformities, although confounding factors affecting bone homeostasis are likely.⁴ In children, there is currently inadequate information whether repeated FCM doses leads to recurrent acute or cumulative chronic hypophosphataemia.

Transient moderate to severe hypophosphataemia can occur following FCM but severe cases with clinical consequences are rare. Patients and clinicians should be alert for symptoms that may suggest hypophosphataemia in days to weeks following FCM (unexplained fatigue, muscle weakness, bone pain, fractures) and check serum phosphate level if hypophosphataemia is suspected. Concomitant risk factors for disorders of phosphate homeostasis may contribute to risk and should be identified and addressed, particularly in children requiring repeated infusions. Further quality research is needed to determine frequency of hypophosphataemia post-FCM in children and establish its clinical importance.

Informed written consent has been obtained from the patient.

中文翻译：

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羧基麦芽糖铁输注后的低磷酸盐血症

羧基麦芽糖铁输注后的低磷酸盐血症

当口服铁制剂不能耐受、无效或禁忌时，静脉补铁用于治疗缺铁性贫血。羧基麦芽糖铁 (FCM)（Ferinject，Vifor Pharma Pty Ltd Australia）是一种静脉用铁制剂，获准用于 14 岁以上儿童，具有良好的报告安全性、耐受性和有效性，用于儿科中心，包括以下儿童14年。^1、2

据报道，由于成纤维细胞生长因子 23 增加导致肾小管磷酸盐重吸收减少并持续数周至数月，因此在输铁后会出现暂时性低磷酸盐血症。³我们观察到，经常开 FCM 的处方者不知道低磷酸盐血症是一种可能的不良反应，但是，这是考虑铁输注后患者出现严重难治性或有症状的低磷酸盐血症的重要区别。

我们报告了一名患有克罗恩病的 17 岁女性，她在 FCM 输注后 12 天出现部分小肠梗阻、心动过缓、低血压和疲劳。血液显示严重的低磷酸盐血症（0.30 mmol/L）。规定了静脉磷酸盐校正，并对她进行了保守治疗。第二天发现血清磷酸盐增加最小，她需要在接下来的 5 天内每天静脉注射磷酸盐校正。入院第 6 天，她的血清磷酸盐仍然很低（0.59 mmol/L）。配对的尿液和血清样本显示磷酸盐排泄分数升高 (38%)，证实肾磷酸盐消耗。她通过口服磷酸盐补充剂出院，并且她的血清磷酸盐在 FCM 后第 22 天恢复正常。

目前关于铁诱导的急性低磷血症的临床意义的证据是相互矛盾的。在成人研究中，绝大多数受影响的个体是无症状的；然而，病例报告描述了无法解释的疲劳、嗜睡和肌肉无力。³

成人在重复 FCM 剂量后记录到慢性低磷酸盐血症，有骨软化和骨畸形的病例报告，尽管可能存在影响骨稳态的混杂因素。⁴在儿童中，目前没有足够的信息表明反复服用 FCM 是否会导致复发性急性或累积性慢性低磷血症。

FCM 后可能发生短暂的中度至重度低磷血症，但具有临床后果的严重病例很少见。患者和临床医生应警惕 FCM 后数天至数周内可能提示低磷酸盐血症的症状（不明原因的疲劳、肌肉无力、骨痛、骨折），并在怀疑低磷酸盐血症时检查血清磷酸盐水平。磷酸盐稳态失调的伴随风险因素可能会增加风险，应予以识别和解决，特别是在需要反复输注的儿童中。需要进一步的质量研究来确定儿童 FCM 后低磷酸盐血症的频率并确定其临床重要性。

已获得患者的知情书面同意。