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抗甲状腺药物相关的严重中性粒细胞减少症和粒细胞缺乏症:在单一参考中心管理的30例病例研究

Severe Neutropenia and Agranulocytosis Related to Antithyroid Drugs: A Study of 30 Cases Managed in A Single Reference Center.

作者信息

Andrès Emmanuel, Lorenzo Villalba Noel, Mourot-Cottet Rachel, Maloisel Frédéric, Tebacher Martine, Gottenberg Jacques-Eric, Goichot Bernard, Herbrecht Raoul, Zulfiqar Abrar-Ahmad

机构信息

Departments of Internal Medicine, Strasbourg University Hospitals, 67000 Strasbourg, France.

Onco-Hematology, Strasbourg University Hospitals, 67000 Strasbourg, France.

出版信息

Medicines (Basel). 2020 Mar 19;7(3):15. doi: 10.3390/medicines7030015.

Abstract

The most important series devoted to antithyroid drug-induced severe neutropenia and agranulocytosis are Japanese studies, almost specifically in relation to the intake of methimazole. The clinical data of 30 Caucasian patients followed up for antithyroid drug-induced neutropenia at a third-level hospital are reported. The data of 30 patients with idiosyncratic antithyroid drug-induced neutropenia and agranulocytosis from a cohort study on drug-induced neutropenia and agranulocytosis conducted at the University Hospital of Strasbourg (France) were retrospectively reviewed. The mean patient age was 61.7 years old (range: 20-87), and the gender ratio (F/M) was 4. Several comorbidities were reported in 23 patients (76.7%), with the mean Charlson comorbidity index of 1. The causative drugs were carbimazole and benzylthiouracil, in 28 (93.3%) and 2 cases, respectively, prescribed primarily for multi-hetero-nodular goiter or thyroid nodule to 18 patients (60%). Sore throat and acute tonsillitis (40%), isolated fever (20%), septicemia (13.3%), documented pneumonia (6.7%), and septic shock (6.7%) were the main clinical features upon admission. The mean neutrophil count at nadir was 0.02 and 0 × 10/L (range: 0-0.3). Regarding the patients' hospital course: 13 cases (43.3%) worsened during hospitalization, severe sepsis was found in 26.7%, systemic inflammatory response syndrome-in 13.3%, and septic shock-in 3.3% of the cases, respectively. Broad-spectrum antibiotics were indicated for all the patients, and 21 (73.3%) of them received hematopoietic growth factors. Hematological recovery (neutrophil count ≥ 1.5 × 10/L) was seen at 8.3 days (range: 2-24), but faster in those receiving hematopoietic growth factors (4.9 days, = 0.046). Two patients died during hospitalization, and the rest had a favorable clinical outcome. Antithyroid drug-induced neutropenia represents a serious complication resulting from the rates of severe infections especially in those cases severe neutropenia. In this setting, an established procedure for the management of patients seems useful or even indispensable in view of potential mortality.

摘要

关于抗甲状腺药物引起的严重中性粒细胞减少症和粒细胞缺乏症的最重要系列研究是日本的研究,几乎专门针对甲巯咪唑的摄入情况。报告了一家三级医院对30例因抗甲状腺药物引起中性粒细胞减少症进行随访的白种人患者的临床数据。回顾性分析了法国斯特拉斯堡大学医院进行的一项关于药物性中性粒细胞减少症和粒细胞缺乏症队列研究中30例因特异质性抗甲状腺药物引起中性粒细胞减少症和粒细胞缺乏症患者的数据。患者平均年龄为61.7岁(范围:20 - 87岁),性别比(女/男)为4。23例患者(76.7%)报告有多种合并症,Charlson合并症指数平均为1。致病药物分别为卡比马唑和苄基硫氧嘧啶,各有28例(93.3%)和2例,主要用于治疗18例(60%)多结节性甲状腺肿或甲状腺结节患者。入院时的主要临床特征为咽痛和急性扁桃体炎(40%)、单纯发热(20%)、败血症(13.3%)、确诊肺炎(6.7%)和感染性休克(6.7%)。中性粒细胞计数最低点时的平均值为0.02和0×10⁹/L(范围:0 - 0.3)。关于患者的住院病程:13例(43.3%)在住院期间病情恶化,分别有26.7%的患者发生严重脓毒症、13.3%的患者发生全身炎症反应综合征、3.3%的患者发生感染性休克。所有患者均使用了广谱抗生素,其中21例(73.3%)接受了造血生长因子治疗。血液学恢复(中性粒细胞计数≥1.5×10⁹/L)出现在8.3天(范围:2 - 24天),但接受造血生长因子治疗的患者恢复更快(4.9天,P = 0.046)。2例患者在住院期间死亡,其余患者临床结局良好。抗甲状腺药物引起的中性粒细胞减少症是一种严重并发症,尤其是在严重中性粒细胞减少症患者中,严重感染发生率较高。在这种情况下,鉴于潜在的死亡率,建立一套患者管理程序似乎是有用的,甚至是必不可少

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