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青少年非抗凝依赖的华法林过量:逆转策略和药代动力学。

Warfarin Overdose in an Adolescent Not Dependent on Anticoagulation: Reversal Strategy and Kinetics.

机构信息

Department of Emergency Medicine, Maine Medical Center, 22 Bramhall Street, Portland, ME, 04102, USA.

Harvard Medical Toxicology Program, Boston Children's Hospital, 300 Longwood Avenue, Mailstop 3025, Boston, MA, 02115, USA.

出版信息

J Med Toxicol. 2022 Oct;18(4):334-339. doi: 10.1007/s13181-022-00907-1. Epub 2022 Sep 6.

Abstract

INTRODUCTION

Warfarin induces coagulopathy. Guidelines protocolize reversal of supratherapeutic international normalized ratio (INR) in patients dependent on anticoagulation, but practices vary for reversing warfarin-induced coagulopathy after overdose in non-warfarin-dependent patients.

CASE REPORT

This is the report of a 15-year-old female who ingested her father's warfarin (100-200 mg) in a self-harm attempt. At hour 24 post-ingestion, her INR was 2.00 and she was admitted for monitoring. Reversal of coagulopathy was initially deferred pending the INR trend. The INR was 5.10 at hour 60 and 2.5 mg oral vitamin K (VK1) was given. At hour 85, the INR peaked at 6.67 and she received a second oral dose of 2.5 mg VK1. On day 8, she was medically cleared with an INR of 1.31. On day 11, she developed lower abdominal pain and diarrhea. Imaging revealed a duodenal hematoma, and symptoms improved spontaneously. She was again medically cleared 13 days post-ingestion. Her serum warfarin concentration peaked at 19 mcg/mL at hour 46. Serial warfarin concentrations were obtained, demonstrating first-order elimination kinetics and a 30-hour half-life.

CONCLUSION

A restrictive approach to coagulopathy reversal in non-warfarin-dependent patients with intentional warfarin overdose may result in worsening coagulopathy, bleeding, and lengthy hospital stay. Given the risk for significant, prolonged coagulopathy, these patients should be treated early with VK1, with subsequent serial INR monitoring and probable additional VK1 dosing. Delayed peak warfarin concentrations support consideration of gastrointestinal decontamination in late presenters.

摘要

简介

华法林可引起凝血功能障碍。指南规定了对抗依赖抗凝治疗的超治疗国际标准化比值(INR)的逆转方案,但对于非华法林依赖患者过量服用华法林后凝血功能障碍的逆转方案,实践中存在差异。

病例报告

这是一名 15 岁女性的报告,她在自残时摄入了父亲的华法林(100-200mg)。摄入后 24 小时,INR 为 2.00,她被收入院进行监测。最初推迟了凝血功能障碍的逆转,等待 INR 趋势。摄入后 60 小时 INR 为 5.10,给予口服 2.5mg 维生素 K(VK1)。摄入后 85 小时,INR 峰值为 6.67,给予第二次口服 2.5mg VK1。第 8 天,INR 为 1.31,她获准出院。第 11 天,她出现下腹痛和腹泻。影像学显示十二指肠血肿,症状自行改善。摄入后 13 天再次获准出院。她的血清华法林浓度在摄入后 46 小时达到 19 mcg/mL 的峰值。获得了一系列华法林浓度,显示出一级消除动力学和 30 小时半衰期。

结论

对于故意华法林过量的非华法林依赖患者,采用限制抗凝逆转的方法可能导致凝血功能障碍、出血和住院时间延长。鉴于存在严重、长期凝血功能障碍的风险,这些患者应早期给予 VK1,随后进行连续 INR 监测,并可能需要额外的 VK1 剂量。延迟的华法林峰值浓度支持考虑在晚期出现的患者进行胃肠道去污。

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本文引用的文献

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Warfarin Poisoning with Delayed Rebound Toxicity.华法林中毒伴延迟性反弹性毒性
J Emerg Med. 2017 Feb;52(2):194-196. doi: 10.1016/j.jemermed.2016.05.068. Epub 2016 Nov 9.
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Warfarin overdose: a 25-year experience.华法林过量:25年的经验
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An update of consensus guidelines for warfarin reversal.华法林逆转共识指南更新。
Med J Aust. 2013 Mar 4;198(4):198-9. doi: 10.5694/mja12.10614.
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Guidelines on oral anticoagulation with warfarin - fourth edition.华法林口服抗凝治疗指南 - 第四版
Br J Haematol. 2011 Aug;154(3):311-24. doi: 10.1111/j.1365-2141.2011.08753.x. Epub 2011 Jun 14.
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Intentional warfarin overdose.故意过量服用华法林。
Ther Drug Monit. 2003 Dec;25(6):715-22. doi: 10.1097/00007691-200312000-00010.

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