An Outbreak of Synthetic Cannabinoid–Associated Coagulopathy in Illinois,The New England Journal of Medicine

Background

In March and April 2018, more than 150 patients presented to hospitals in Illinois with coagulopathy and bleeding diathesis. Area physicians and public health organizations identified an association between coagulopathy and synthetic cannabinoid use. Preliminary tests of patient serum samples and drug samples revealed that brodifacoum, an anticoagulant, was the likely adulterant.

Methods

We reviewed physician-reported data from patients admitted to Saint Francis Medical Center in Peoria, Illinois, between March 28 and April 21, 2018, and included in a case series adult patients who met the criteria used to diagnose synthetic cannabinoid–associated coagulopathy. A confirmatory anticoagulant poisoning panel was ordered at the discretion of the treating physician.

Results

A total of 34 patients were identified as having synthetic cannabinoid–associated coagulopathy during 45 hospitalizations. Confirmatory anticoagulant testing was performed in 15 of the 34 patients, and superwarfarin poisoning was confirmed in the 15 patients tested. Anticoagulant tests were positive for brodifacoum in 15 patients (100%), difenacoum in 5 (33%), bromadiolone in 2 (13%), and warfarin in 1 (7%). Common symptoms at presentation included gross hematuria in 19 patients (56%) and abdominal pain in 16 (47%). Computed tomography was performed to evaluate abdominal pain and revealed renal abnormalities in 12 patients. Vitamin K1 (phytonadione) was administered orally in all 34 patients and was also administered intravenously in 23 (68%). Red-cell transfusion was performed in 5 patients (15%), and fresh-frozen plasma infusion in 19 (56%). Four-factor prothrombin complex concentrate was used in 1 patient. One patient died from complications of spontaneous intracranial hemorrhage.

Conclusions

Our data indicate that superwarfarin adulterants of synthetic cannabinoids can lead to clinically significant coagulopathy. In our series, in most of the cases in which the patient presented with bleeding diathesis, symptoms were controlled with the use of vitamin K1 replacement therapy. The specific synthetic cannabinoid compounds are not known.

中文翻译：

伊利诺伊州爆发的大麻素相关性凝血病暴发

背景

在2018年3月和2018年4月，伊利诺伊州有150多名患有凝血病和出血性疾病的医院就诊。地区医生和公共卫生组织确定了凝血病和合成大麻素使用之间的关联。对患者血清样品和药物样品的初步测试表明，抗凝剂溴地芬很可能会掺假。

方法

我们回顾了2018年3月28日至4月21日之间从伊利诺伊州皮奥里亚（Peoria）的圣弗朗西斯医学中心（Saint Francis Medical Center）入院的患者的医生报告数据，并将这些患者纳入病例组，这些患者符合用于诊断合成大麻素相关性凝血病的标准。经治疗医师酌情下令确认性抗凝中毒专家小组下达命令。

结果

在45例住院期间，共有34例患者被确定患有合成大麻素相关性凝血病。在34例患者中的15例中进行了确诊性抗凝试验，在15例患者中证实了超华法林中毒。抗凝试验阳性的15例患者（100％）的溴地芬，5例（33％）的地芬那浓，2例（13％）的苯丁二酮和1例（7％）的华法林。呈现的常见症状包括19例（56％）的肉眼血尿和16例（47％）的腹痛。进行计算机断层扫描以评估12例患者的腹痛并显示肾脏异常。在所有34例患者中口服维生素K1（植物酮），也有23例（68％）通过静脉给药。5例（15％）进行了红细胞输注，19例（56％）进行了新鲜冷冻血浆输注。1名患者使用了四因子凝血酶原复合物浓缩物。一名患者死于自发性颅内出血并发症。

结论

我们的数据表明，合成大麻素的超华法林掺假可导致临床上明显的凝血病。在我们的系列文章中，在大多数患者表现出大出血的情况下，使用维生素K1替代疗法可控制症状。具体的合成大麻素化合物尚不清楚。

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