Unmet clinical laboratory need in patients hospitalized for acute poisoning from long-acting anticoagulant rodenticides.

Unmet clinical laboratory need in patients hospitalized for acute poisoning from long-acting anticoagulant rodenticides.
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DOI:
10.1080/24734306.2021.1925444
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发表时间:
2021
影响因子:
--
通讯作者:
Rubinstein I
Rubinstein I
中科院分区:
其他
文献类型:
--
作者:
van Breemen RB;Hafner JW;Nosal DG;Feinstein DL;Rubinstein I

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在2018年伊利诺伊州爆发的严重凝血病期间,医生治疗中毒患者的实时,定量毒理学数据的重要性得到了说明,该疾病是由吸入被市售溴鼠灵,地芬那鼠灵和溴敌隆污染的非法合成大麻素产品引起的,三种强效,长效抗凝血灭鼠剂(LAAR)。在住院患者的血液样本中鉴定和定量这些危及生命的毒素需要用液相色谱-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可提供关键信息,以指导住院期间和住院后的患者护理,包括识别违规LAAR,估计摄入剂量,以及一旦血浆LAAR浓度降至安全水平(<10 ng/mL),出院后口服维生素K1治疗的剂量和停止。因此,我们提出了一个行动计划,使治疗医生定量血浆浓度的几个LAAR同时中毒患者。它涉及我们实验室开发、测试和验证的快速(<15分钟)、灵敏和经验证的LC-MS/MS方法。这将允许治疗医生要求定量血浆LAAR检测,在患者的出院总结中报告检测结果,并建议在门诊环境中定期监测血浆LAAR浓度。
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.