From the Departments of Medicine (A.H.K., N.A.S., A.M., H.M., M.D.T.) and Pediatrics (M.D.T., J.C.R.), University of Illinois College of Medicine at Peoria, and the Bleeding and Clotting Disorders Institute (M.D.T., J.C.R.) - both in Peoria.
N Engl J Med. 2018 Sep 27;379(13):1216-1223. doi: 10.1056/NEJMoa1807652.
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.
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.
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 K (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.
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 K replacement therapy. The specific synthetic cannabinoid compounds are not known.
2018 年 3 月和 4 月，伊利诺伊州的多家医院接诊了 150 多名出现凝血功能障碍和出血倾向的患者。当地医生和公共卫生组织发现，凝血功能障碍与合成大麻素的使用之间存在关联。对患者血清样本和药物样本的初步检测显示，可能的掺杂物是一种抗凝剂——溴敌隆。
我们回顾了 2018 年 3 月 28 日至 4 月 21 日期间入住伊利诺伊州皮奥里亚圣弗朗西斯医疗中心的患者的医生报告数据，并将符合诊断合成大麻素相关凝血功能障碍标准的成年患者纳入病例系列。主治医生可决定进行确认性抗凝剂中毒检测。
在 45 次住院治疗中，共有 34 名患者被确定患有合成大麻素相关凝血功能障碍。在 34 名患者中，有 15 名进行了确认性抗凝剂检测，其中 15 名检测呈超华法林中毒阳性。15 名（100%）患者的抗凝剂检测呈溴敌隆阳性，5 名（33%）患者呈敌鼠钠盐阳性，2 名（13%）患者呈溴鼠灵阳性，1 名（7%）患者呈华法林阳性。患者就诊时的常见症状包括 19 名（56%）肉眼血尿和 16 名（47%）腹痛。为评估腹痛进行了计算机断层扫描，发现 12 名患者存在肾脏异常。所有 34 名患者均接受了口服维生素 K（叶绿醌）治疗，23 名（68%）患者还接受了静脉注射治疗。5 名（15%）患者接受了红细胞输注，19 名（56%）患者接受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。1 名患者因自发性颅内出血并发症死亡。
我们的数据表明，合成大麻素中的超华法林掺杂物可导致严重的凝血功能障碍。在我们的研究中，在大多数出现出血倾向的患者中，症状通过维生素 K 替代治疗得到控制。具体的合成大麻素化合物尚不清楚。
