Division of Hematology Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.
Division of Hematology Oncology, Massachusetts General Hospital, Boston, MA.
Blood Adv. 2024 Nov 12;8(21):5451-5457. doi: 10.1182/bloodadvances.2024013666.
Iron overload and its complications are recognized to be morbid and fatal in patients with congenital hemolytic anemias. In patients with iron overload caused by congenital hemolytic anemias, there has been no study evaluating the dose-response relationship between serum markers of iron overload and long-term health complications. Filling this critical gap was the aim of this study. We evaluated outcomes in a 5-hospital observational cohort study of adults with congenital hemolytic anemias diagnosed with iron overload over a 40-year period and assessed associations between depth and duration of iron overload, as well as clinical complications including diabetes, heart disease, malignancy, bone density disorders, and death. One hundred seventy patients with congenital hemolytic anemias developing iron overload were included. More years experienced of ferritin >500 ng/mL and >1000 ng/mL were associated with the development of diabetes mellitus, with adjusted odds ratios (ORs) of 2.61 per 10-year increment (P = .034) and 3.24 per 10-year increment (P = .035), respectively. More years experienced of ferritin >1000 ng/mL were associated with the development of heart disease (adjusted OR, 5.30 per 10-year increment; P = .002). Peak lifetime ferritin of >10 000 ng/mL was associated with sixfold odds of developing diabetes (P = .04) and 10-fold odds of developing heart disease (P = .007). A peak ferritin >10 000 ng/mL was associated with an increase in mortality (adjusted OR, 6.77; P = .033). In conclusion, iron overload in patients with congenital hemolytic anemias is associated with diabetes mellitus, cardiac disease, and death. Prolonged exposure to relatively modest iron overload was associated with nearly threefold increased odds of diabetes.
铁过载及其并发症被认为在先天性溶血性贫血患者中是病态和致命的。在由先天性溶血性贫血引起的铁过载患者中，尚未有研究评估铁过载血清标志物与长期健康并发症之间的剂量反应关系。填补这一关键空白是本研究的目的。我们评估了一项为期 40 年的、在 5 家医院进行的先天性溶血性贫血成人铁过载观察队列研究的结果，并评估了铁过载深度和持续时间与包括糖尿病、心脏病、恶性肿瘤、骨密度紊乱和死亡在内的临床并发症之间的相关性。纳入了 170 例发生铁过载的先天性溶血性贫血患者。血清铁蛋白 >500ng/mL 和 >1000ng/mL 的时间每增加 10 年与糖尿病的发生相关，校正后的比值比（OR）分别为 2.61（P=.034）和 3.24（P=.035）。血清铁蛋白 >1000ng/mL 的时间每增加 10 年与心脏病的发生相关（校正 OR，5.30/10 年；P=.002）。峰值终身铁蛋白 >10000ng/mL 与发生糖尿病的六倍几率相关（P=.04）和发生心脏病的十倍几率相关（P=.007）。峰值铁蛋白 >10000ng/mL 与死亡率增加相关（校正 OR，6.77；P=.033）。总之，先天性溶血性贫血患者的铁过载与糖尿病、心脏病和死亡有关。长期接触相对适度的铁过载与糖尿病发生的几率增加近三倍相关。
