Background Direct oral anticoagulants (DOAC) are increasingly used worldwide. Little is known so far about their pharmacokinetics in emergency situations. Methods A prospective, observational registry was performed to determine the clinical course in consecutive patients with major bleeding or urgent surgery treated with DOACs. In back-up blood samples from routine care DOAC drug concentrations were measured using UPLC-MS/MS. Anticoagulant intensity at first presentation and drug half-life (t1/2), tested in repeat samples, were evaluated. Results 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. 67% (89/132) experienced life-threatening bleeding and 33% (43/132) needed an urgent surgery. For pharmacokinetic analysis a total of 605 blood samples was available. Median concentration on admission was 205 ng/mL for rivaroxaban and 108 ng/mL for apixaban. All treatment groups showed a high variation of drug concentrations at baseline. In rivaroxaban treated patients t½ was 17.3 hours (95% CI: 15.4 – 19.7) without significant difference in both groups (major bleeding: t½ 16.7 hours, 95% CI: 14.7 - 19.3; urgent surgery: t½ 19.7 hours, 95% CI 15.2 - 27.9; p=0.292). In apixaban treated patients t½ was 25.0 hours (95% CI: 22.9 – 27.6) with a longer t½ after urgent surgery (t1/2: 30.8 hours; 95% CI: 26.9 – 36.4) compared to severe bleeding (t1/2: 20.8 hours; 95% CI: 18.8 – 23.2; p<0.001). Conclusions Emergency patients under DOAC treatment show a high variation of anticoagulant concentrations at baseline. Compared with rivaroxaban, apixaban showed a lower median concentration on admission and a longer t½.

中文翻译：

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紧急情况下直接口服抗凝剂的药代动力学——前瞻性观察性 RADOA 登记结果

背景 直接口服抗凝剂 (DOAC) 在世界范围内的使用越来越多。到目前为止，人们对它们在紧急情况下的药代动力学知之甚少。方法 进行了一项前瞻性观察性登记，以确定连续接受 DOAC 治疗的大出血或紧急手术患者的临床过程。在来自常规护理的备用血液样本中，使用 UPLC-MS/MS 测量 DOAC 药物浓度。评估了首次就诊时的抗凝强度和药物半衰期 (t1/2)，并在重复样本中进行了测试。结果前瞻性纳入了 140 名患者。94% (132/140) 的患者可获得药代动力学数据。67% (89/132) 经历过危及生命的出血，33% (43/132) 需要紧急手术。对于药代动力学分析，共有 605 份血样可供使用。入院时利伐沙班的中位浓度为 205 ng/mL，阿哌沙班为 108 ng/mL。所有治疗组在基线时都显示出药物浓度的高变化。在利伐沙班治疗的患者中，t½ 为 17.3 小时（95% CI：15.4 – 19.7），两组无显着差异（大出血：t½ 16.7 小时，95% CI：14.7 - 19.3；紧急手术：t½ 19.7 小时，95% CI 15.2 - 27.9；p=0.292）。在接受阿哌沙班治疗的患者中，t½ 为 25.0 小时（95% CI：22.9 – 27.6），与严重出血（t1/2：20.8）相比，紧急手术后的 t½ 更长（t1/2：30.8 小时；95% CI：26.9 – 36.4）小时；95% CI：18.8 – 23.2；p<0.001）。结论 接受 DOAC 治疗的急诊患者在基线时表现出抗凝剂浓度的高度变化。与利伐沙班相比，阿哌沙班入院时的中位浓度较低，t½ 较长。