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口服抗凝剂治疗患者严重出血的管理:急诊医学心脏研究与教育集团-国际多学科严重出血共识小组2018年10月20日会议纪要

Management of Severe Bleeding in Patients Treated With Oral Anticoagulants: Proceedings Monograph From the Emergency Medicine Cardiac Research and Education Group-International Multidisciplinary Severe Bleeding Consensus Panel October 20, 2018.

作者信息

Gibler W Brian, Racadio Judy M, Hirsch Amy L, Roat Todd W

出版信息

Crit Pathw Cardiol. 2019 Sep;18(3):143-166. doi: 10.1097/HPC.0000000000000181.

Abstract

In this Emergency Medicine Cardiac Research and Education Group (EMCREG)-International Proceedings Monograph from the October 20, 2018, EMCREG-International Multidisciplinary Consensus Panel on Management of Severe Bleeding in Patients Treated With Oral Anticoagulants held in Orlando, FL, you will find a detailed discussion regarding the treatment of patients requiring anticoagulation and the reversal of anticoagulation for patients with severe bleeding. For emergency physicians, critical care physicians, hospitalists, cardiologists, internists, surgeons, and family physicians, the current approach and disease indications for treatment with anticoagulants such as coumadin, factor IIa, and factor Xa inhibitors are particularly relevant. When a patient treated with anticoagulants presents to the emergency department, intensive care unit, or operating room with severe, uncontrollable bleeding, achieving rapid, controlled hemostasis is critically important to save the patient's life. This EMCREG-International Proceedings Monograph contains multiple sections reflecting critical input from experts in Emergency Cardiovascular Care, Prehospital Emergency Medical Services, Emergency Medicine Operations, Hematology, Hospital Medicine, Neurocritical Care, Cardiovascular Critical Care, Cardiac Electrophysiology, Cardiology, Trauma and Acute Care Surgery, and Pharmacy. The first section provides a description of the current indications for the treatment of patients using oral anticoagulants including coumadin, the factor IIa (thrombin) inhibitor dabigatran, and factor Xa inhibitors such as apixaban and rivaroxaban. In the remaining sections, the treatment of patients presenting to the hospital with major bleeding becomes the focus. The replacement of blood components including red blood cells, platelets, and clotting factors is the critically important initial treatment for these individuals. Reversing the anticoagulated state is also necessary. For patients treated with coumadin, infusion of vitamin K helps to initiate the process of protein synthesis for the vitamin K-dependent coagulation proteins II, VII, IX, and X and the antithrombotic protein C and protein S. Repletion of clotting factors for the patient with 4-factor prothrombin complex concentrate, which includes factors II (prothrombin), VII, IX, and X and therapeutically effective concentrations of the regulatory proteins (protein C and S), provides real-time ability to slow bleeding. For patients treated with the thrombin inhibitor dabigatran, treatment using the highly specific, antibody-derived idarucizumab has been demonstrated to reverse the hypocoagulable state of the patient to allow blood clotting. In May 2018, andexanet alfa was approved by the US Food and Drug Administration to reverse the factor Xa anticoagulants apixaban and rivaroxaban in patients with major bleeding. Before the availability of this highly specific agent, therapy for patients treated with factor Xa inhibitors presenting with severe bleeding usually included replacement of lost blood components including red blood cells, platelets, and clotting factors and 4-factor prothrombin complex concentrate, or if not available, fresh frozen plasma. The evaluation and treatment of the patient with severe bleeding as a complication of oral anticoagulant therapy are discussed from the viewpoint of the emergency physician, neurocritical and cardiovascular critical care intensivist, hematologist, trauma and acute care surgeon, hospitalist, cardiologist, electrophysiologist, and pharmacist in an approach we hope that the reader will find extremely practical and clinically useful. The clinician learner will also find the discussion of the resumption of oral anticoagulation for the patient with severe bleeding after effective treatment important because returning the patient to an anticoagulated state as soon as feasible and safe prevents thrombotic complications. Finally, an EMCREG-International Severe Bleeding Consensus Panel algorithm for the approach to management of patients with life-threatening oral anticoagulant-associated bleeding is provided for the clinician and can be expanded in size for use in a treatment area such as the emergency department or critical care unit.

摘要

在这本来自2018年10月20日于佛罗里达州奥兰多举行的急诊医学心脏研究与教育小组(EMCREG)-口服抗凝剂治疗患者严重出血管理国际多学科共识小组的急诊医学心脏研究与教育小组(EMCREG)国际会议论文集中,你会发现关于需要抗凝治疗的患者的治疗以及严重出血患者抗凝逆转的详细讨论。对于急诊医生、重症监护医生、住院医生、心脏病专家、内科医生、外科医生和家庭医生来说,使用香豆素、凝血因子IIa和凝血因子Xa抑制剂等抗凝剂的当前治疗方法和疾病适应症尤为相关。当接受抗凝治疗的患者因严重、无法控制的出血而前往急诊科、重症监护病房或手术室时,实现快速、可控的止血对于挽救患者生命至关重要。这本EMCREG国际会议论文集包含多个章节,反映了急诊心血管护理、院前急救医疗服务、急诊医学操作、血液学、医院医学、神经重症监护、心血管重症监护、心脏电生理学、心脏病学、创伤与急性护理外科以及药学等领域专家的重要意见。第一部分描述了目前使用口服抗凝剂治疗患者的适应症,包括香豆素、凝血因子IIa(凝血酶)抑制剂达比加群以及凝血因子Xa抑制剂如阿哌沙班和利伐沙班。在其余章节中,以严重出血症状入院的患者的治疗成为重点。对于这些患者,补充包括红细胞、血小板和凝血因子在内的血液成分是至关重要的初始治疗方法。逆转抗凝状态也是必要的。对于接受香豆素治疗的患者,输注维生素K有助于启动维生素K依赖的凝血蛋白II、VII、IX和X以及抗血栓蛋白C和蛋白S的蛋白质合成过程。使用含有凝血因子II(凝血酶原)、VII、IX和X以及治疗有效浓度的调节蛋白(蛋白C和S)的四因子凝血酶原复合物浓缩物补充凝血因子,能够实时减缓出血。对于接受凝血酶抑制剂达比加群治疗的患者,已证明使用高度特异性的、源自抗体的依达赛珠单抗进行治疗可逆转患者的低凝状态,从而实现血液凝固。2018年5月,andexanet alfa被美国食品药品监督管理局批准用于逆转大出血患者体内的凝血因子Xa抗凝剂阿哌沙班和利伐沙班的作用。在这种高度特异性药物出现之前,接受凝血因子Xa抑制剂治疗且出现严重出血的患者的治疗通常包括补充丢失的血液成分,如红细胞、血小板和凝血因子以及四因子凝血酶原复合物浓缩物,若无法获得该浓缩物,则使用新鲜冰冻血浆。本文从急诊医生、神经重症和心血管重症监护专家、血液学家、创伤与急性护理外科医生、住院医生、心脏病专家、电生理学家和药剂师的角度,讨论了作为口服抗凝剂治疗并发症的严重出血患者的评估和治疗方法,我们希望读者会发现这种方法极其实用且具有临床价值。临床学习者还会发现,对于有效治疗后严重出血患者恢复口服抗凝治疗的讨论很重要,因为在可行且安全的情况下尽快使患者恢复抗凝状态可预防血栓形成并发症。最后,为临床医生提供了一份EMCREG国际严重出血共识小组关于危及生命的口服抗凝剂相关出血患者管理方法的算法,该算法可放大尺寸以便在急诊科或重症监护病房等治疗区域使用。

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