Centre of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Eur J Clin Pharmacol. 2012 May;68(5):821-32. doi: 10.1007/s00228-011-1184-3. Epub 2011 Dec 21.
Drug-induced immune thrombocytopaenia is a rare, serious condition that can be triggered by numerous medications. To characterize the spectrum of drugs associated with immune thrombocytopaenia (ITP) in the Berlin Case-Control Surveillance Study (FAKOS).
Adult hospitalized patients with new onset idiopathic, secondary or drug-induced acute ITP and hospital control patients were ascertained by active surveillance in 50 Berlin hospitals (>180 clinical departments) between 2000 and 2009. Drug exposures were obtained in a personal interview. Chronic cases were excluded in a follow-up after 6 or more months. A standardized causality assessment was conducted for each ITP patient to assess possible drug aetiology. Drug risks were quantified in a case-control design with unconditional logistic regression analysis.
Ninety out of 169 validated cases of acute ITP were assessed as being at least possibly drug-related (n= 85 different drugs overall, n = 30 drugs with certain or probable causality). Drugs involved in ≥ 2 cases with a probable or certain relationship were tirofiban (n = 10 cases), abciximab (n = 4), trimethoprim/sulphamethoxazole (n = 4), influenza vaccine (n = 3), and citalopram (n = 2). Pneumococcal and poliomyelitis vaccine were assessed as probably causing ITP in one case each. In the case-control analyses, significantly increased risks were observed for tirofiban, abciximab, trimethoprim/sulphamethoxazole, gentamicin, triamterene/hydrochlorothiazide, drospirenone/ethinylestradiol, and influenza vaccination.
Our study confirms known ITP risks for glycoprotein IIb/IIIa receptor antagonists and sulphonamides and generates signals for several other drugs and vaccines. New onset of ITP should not only direct attention to drugs as possible aetiological agents, but also to vaccines that are known to cause autoimmune phenomena.
药物诱导的免疫性血小板减少症是一种罕见且严重的病症,可由多种药物引发。本研究旨在通过柏林病例对照监测研究(FAKOS),对与免疫性血小板减少症(ITP)相关的药物谱进行特征描述。
本研究通过主动监测,于 2000 年至 2009 年在柏林的 50 家医院(180 余个临床科室)中,确定了新发病例的特发性、继发性或药物诱导性急性 ITP 成年住院患者以及医院对照患者。通过个人访谈获取药物暴露情况。在 6 个月或更长时间的随访中排除慢性病例。对每位 ITP 患者进行标准化因果关系评估,以评估可能的药物病因。采用病例对照设计,使用非条件逻辑回归分析来量化药物风险。
在 169 例经验证的急性 ITP 病例中,有 90 例被评估为至少可能与药物相关(共涉及 85 种不同药物,其中 30 种药物具有确定或可能的因果关系)。涉及 2 例以上可能或确定关系的药物有替罗非班(n = 10 例)、阿昔单抗(n = 4 例)、甲氧苄啶/磺胺甲噁唑(n = 4 例)、流感疫苗(n = 3 例)和西酞普兰(n = 2 例)。肺炎球菌疫苗和脊髓灰质炎疫苗各有 1 例被评估为可能导致 ITP。在病例对照分析中,替罗非班、阿昔单抗、甲氧苄啶/磺胺甲噁唑、庆大霉素、阿米洛利/氢氯噻嗪、屈螺酮/炔雌醇和流感疫苗的风险显著增加。
本研究证实了已知的 ITP 风险与糖蛋白 IIb/IIIa 受体拮抗剂和磺胺类药物相关,并为其他几种药物和疫苗发出了信号。新出现的 ITP 不仅应引起人们对可能的病因药物的关注,还应关注已知会引起自身免疫现象的疫苗。