长效抗凝血灭鼠剂急性中毒住院患者未满足的临床实验室需求。

Toxicology communications Pub Date : 2021-01-01 Epub Date: 2021-06-04 DOI:10.1080/24734306.2021.1925444
Richard B van Breemen, John W Hafner, Daniel G Nosal, Douglas L Feinstein, Israel Rubinstein
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引用次数: 0

摘要

2018 年,伊利诺伊州爆发了因吸入被市售溴敌隆、敌鼠隆和溴敌隆这三种强效长效抗凝血灭鼠剂(LAARs)污染的非法合成大麻素产品而导致的严重凝血病,这说明了为治疗中毒患者的医生提供实时、定量毒理学数据的重要性。要在住院病人的血液样本中鉴定和量化这些危及生命的毒素,需要使用液相色谱-串联质谱法(LC-MS/MS)进行毒理学检测,而在疫情爆发时,医院的临床实验室还没有这种检测方法。这种高灵敏度的定量检测方法可提供关键信息,指导住院期间和住院后的病人护理,包括确定违规的 LAARs、估计摄入剂量、剂量以及出院后一旦血浆中 LAARs 浓度降至安全水平即停止口服维生素 K1 治疗 (
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Unmet clinical laboratory need in patients hospitalized for acute poisoning from long-acting anticoagulant rodenticides.

The importance of real-time, quantitative toxicology data available for physicians treating poisoned patients was illustrated during the 2018 outbreak in Illinois of severe coagulopathy caused by inhaling illicit synthetic cannabinoids products contaminated with commercially-available brodifacoum, difenacoum, and bromadiolone, three potent, long-acting anticoagulant rodenticides (LAARs). Identification and quantification of these life-threatening toxins in blood samples of hospitalized patients required toxicology testing with liquid chromatography-tandem mass spectrometry (LC-MS/MS) that was not available in clinical laboratories of hospitals at the time of the outbreak. This highly-sensitive, quantitative assay can provide critical information to guide patient care during and after hospitalization, including identification of offending LAARs, estimates of the ingested dose, and dosage and discontinuation of oral vitamin K1 therapy after hospital discharge once plasma LAARs concentrations decreased to a safe level (<10 ng/mL). Accordingly, we propose an action plan to enable treating physicians to quantify plasma concentrations of several LAARs simultaneously in poisoned patients. It involves rapid (<15 min), sensitive, and validated LC-MS/MS methods developed, tested and validated in our laboratory. This will allow treating physicians to request quantitative plasma LAARs testing, report test results in the patient's hospital discharge summary, and recommend regular monitoring of plasma LAARs concentrations in the outpatient setting.

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