抗血栓药物在内镜操作时的管理.doc

Management【管理】 of antithrombotic 【抗血栓形成的】agents 【药剂】for endoscopic【内窥镜检查的】 procedures【程序、操作、步骤、过程】 This is one of a series of statements discussing the use of GI endoscopy 【胃肠内镜检查】in common clinical situations. The Standards【标准】 of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE)【美国胃肠镜协会】 prepared this text. This guideline【指导原则】 combines and updates 2 previously【以前】 issued guidelines, Guideline on the management of antithrombotic and antiplatelet therapy 【抗血小板治疗】for endoscopic procedures1 and ASGE guideline: the management of low-molecular-weight heparin【低分子肝素】 and nonaspirin【非阿司匹林】 antiplatelet agents for endoscopic procedures.2 To prepare this guideline, a search of the medical literature was performed using PubMed【免费搜索引擎，提供生物医学方面的论文搜索以及摘要】. Studies or reports that described fewer than【少于】 10 patients were excluded from analysis if multiple series with more than 10 patients addressing the same issue were available. Additional【额外的】 references【参考】 were obtained【获得】 from the bibliographies【文献】 of the identified【确认】 articles and from recommendations【推荐、建议】 of expert consultants【专家顾问】. Guidelines for appropriate【合适的】 use of endoscopy are based on a critical review【批评性审查】 of the available data and expert consensus【一致同意】 at the time the guidelines are drafted【制定、起草】. Further controlled clinical studies may be needed to clarify【使清楚，澄清】 aspects【方面】 of this guideline. This guideline may be revised【修订、修正】 as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations【推荐、建议】 are based on reviewed studies【综述研究】 and were graded on【被分级】 the strength of the supporting evidence (Table 1).3 The strength of individual【个人的、独特的】 recommendations is based on both the aggregate【总数的、总计的】 evidence quality and an assessment【评估、评价】 of the anticipated【预先的、预期的】 benefits and harms. Weaker【微弱的、无说服力的】 recommendations are indicated by phrases such as “we suggest” whereas stronger recommendations are typically stated as “we recommend.”TABLE 1. GRADE system for rating the quality of evidence for guidelinesQuality of evidence Definition【定义】 SymbolHigh qualityFurther research is very unlikely to change our confidence in the estimate of effect+Moderate qualityFurther research is likely tohave an important impact onour confidence in the estimateof effect and may change theestimate+-Low qualityFurther research is very likelyto have an important impacton our confidence in the estimateof effect and is likely to changethe estimate+-Very low qualityAny estimate of effect is veryuncertain +-Weaker recommendations are indicated by phrases such as we suggest, whereas stronger recommendations are typically stated as we recommend.Adapted from Guyatt et al.3 This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patients condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from this guideline. Antithrombotic agents include anticoagulants【抗凝剂】 (eg, warfarin, heparin, and low molecular weight heparin) and antiplatelet【抗血小板的】 agents (eg, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), thienopyridines【噻吩并吡啶】 (eg, clopidrogrel【氯吡格雷】 and ticlopidine【噻氯吡啶】), and glycoprotein IIb/IIIa receptor inhibitors【糖蛋白IIb/IIIa受体抑制剂】). Antithrombotic therapy【治疗】 is used to reduce the risk of thromboembolic events【血栓栓塞事件】 in patients with certain【某一，必然的】 cardiovascular【心血管的】 conditions (eg, atrial fibrillation【心房纤颤】 and acute coronary syndrome【ACS急性冠脉综合征】), deep venous thrombosis (DVT)【深部静脉血栓形成】, hypercoagulable states【高凝状态】, and endoprostheses【内镜置管术】. The most common site of significant bleeding in patients receiving oral anticoagulation therapy【口服抗凝治疗】 is the GI tract【胃肠道】.4 The antithrombotic drug classes with【把.与.归入一类】 duration of action and routes for reversal【逆转】 are described in Table 2.TABLE 2. Antithrombotic drugs: duration of action and routes for reversalRoutes for reversalDrug classSpecific agent(s)Duration【持续的时间，持续】 of actionElective【可选择的】Urgent 【极力主张的，急迫的】AntiplateletagentsAspirin10 days NATransfuse platelets【血小板输注】NSAIDsVaries 【相应变化】NATransfuse plateletsDipyridamole【双嘧达莫】2-3 daysHoldTransfuse plateletsThienopyridines (clopidrogrel,【氯吡格雷】 ticlopidine【】噻氯吡啶)3-7 daysNATransfuse platelets desmopressin【去氨加压素】 if overdoseGP IIb/IIIa inhibitors (tirofiban, abciximab, eptifibatide)VariesNATransfuse platelets; in case of overdose, some agents can be removed with dialysis【透析】AnticoagulantsWarfarin3-5 daysHoldFFP vitamin K, consider protamine sulfate*Unfractionated heparin【未分离肝素】4-6 hHoldHold or consider protamine sulfate*LMWH【低分子肝素】12-24 h HoldHold or consider protamine sulfate【硫酸鱼精蛋白】*NA, Not applicable; NSAID, nonsteroidal anti-inflammatory drug; GP, glycoprotein; FFP, fresh frozen plasma; LMWH, low molecular weight heparin.*Caution: Can cause severe hypotension and anaphylaxis. Before performing（【执行】 endoscopic【内镜检查】 procedures on patients taking antithrombotic medications, one should consider the urgency【紧迫，紧要】 of the procedure and the risks of (1) bleeding related solely【唯一地，仅仅】 to antithrombotic therapy, (2) bleeding related to an endoscopic intervention performed in the setting of antithrombotic medication use, and (3) a thromboembolic event related to interruption of antithrombotic therapy. Alternative【备选的，替代的，其他的】 diagnostic【诊断的】 studies for patient evaluation【诊断（医学）；估价】 (eg, video capsule endoscopy【胶囊内镜】 or radiologic studies【放射检查】) should also be considered as well as the use of resources for hospitalization【住院治疗】, parenteral【胃肠外的】 antithrombotic therapy, and laboratory tests【实验室检查】 used to monitor【监测，记录】 antithrombotic therapy.Furthermore, potential【潜在的】 thromboembolic events that may occur with withdrawal【撤回，撤退】 of medication can be devastating【可怕的，毁灭性的】,whereas【鉴于】 bleeding after high-risk procedures, although increased in frequency【频繁性】, is rarely【罕有的】 associated with any significant morbidity【发病率，病态】 or mortality【死亡率，死亡数】. Discussion with the patient and his or her prescribing physician【处方医生】 before the procedure is invaluable【无法估计】 to help determine whether antithrombotic agents should be stopped or adjusted【调整】 in any particular patient. This guideline is an update of two previous ASGE guidelines1,2 and addresses the management of patients undergoing【经历，承受】 endoscopic procedures who are receiving antithrombotic therapy, providing recommendations and management【管理】 algorithms【运算法则】.DEFINITIONS【定义，规定】Procedure risks【操作风险】 Endoscopic procedures vary in their potential to produce significant or uncontrolled bleeding (Table 3).Low-risk procedures include all diagnostic procedures including those with mucosal biopsy【粘膜活检】5,6 and ERCP【内镜逆行胰胆管造影】 without sphincterotomy【括约肌切开术】,7,8 diagnostic balloon-assisted enteroscopy【气囊辅助内镜检查】,9 and EUS 【超声内镜】without FNA 【细针抽吸】or Tru-Cut needle biopsy.10TABLE 3. Procedure risk for bleedingHigher-risk procedures Low-risk proceduresPolypectomy Diagnostic (EGD, colonoscopy, flexible sigmoidoscopy)Biliary or pancreatic sphincterotomy including biopsy Pneumatic or bougie dilation ERCP without sphincterotomy EUS without FNAPEG placement Enteroscopy and diagnostic balloon-assisted enteroscopyTherapeutic balloon-assisted enteroscopy Capsule endoscopy Enteral stent deployment (without dilation) EUS with FNA Endoscopic hemostasisTumor ablation by any techniqueCystogastrostomyTreatment of varices Higher-risk procedures include those associated with an increased risk of bleeding, such as endoscopic polypectomy【内镜息肉切除术】,11,12 therapeutic balloon-assisted enteroscopy,9,13 endoscopic sphincterotomy【内镜下括约肌切开术】,14 and those procedures with the potential to produce bleeding that is inaccessible or uncontrollable【难以或无法控制的】 by endoscopic means such as dilation of benign【良性扩张】 or malignant strictures【恶性狭窄】,15-17 percutaneous endoscopic gastrostomy【经皮内镜胃造口术】,18 and EUS-guided FNA【超声内镜引导下细针穿刺活检术】.19 Finally, patients requiring hemostasis【止血】 should be considered at higher risk of rebleeding regardless of whether their initial【最初的】 procedure was low risk.Condition risks【风险条件】 The probability【概率】 of athromboembolic complication【并发症】 related to the temporary【短暂的，临时的】 interruption【中断】 of antithrombotic therapy for an endoscopic procedure depends on the preexisting 【先前存在的】condition that resulted in the use of antithrombotic therapy.These conditions may be divided into low- and higher risk groups based on their associated risk of thromboembolic events (Table4).Low-risk conditions include DVT【深静脉血栓形成】,chronic【慢性的】 or paroxysmal【阵发性】 atrial【心房的，中庭的】 fibrillation【纤维颤动】 not associated with valvular disease【瓣膜病】,bioprosthetic valves【生物瓣膜】,and mechanical valves【机械瓣膜】 in the aortic 【大动脉】position.Higher-risk conditions include atrial fibrillation associated with valvular heart disease【瓣膜性心脏病】 (whether surgically corrected or not),mechanical valves in the mitral position【二尖瓣位置】,and mechanical valves in patients who have had a previous【先前的、以前的】 thromboembolic event【血栓栓塞事件】. Patients with coronary【冠状动脉】 stents 【支架】(especially those with a drug-eluting stent 【药物释放支架】DES) are at higher risk of stent thrombosis【血栓症】, particularly when dual antiplatelet therapy【双联抗血小板治疗】 (DAT)is discontinued【终止，中断】 before minimum duration recommendations. Current【现在的，最近的】 guidelines【指南，指导方针】 from the American Heart Association (AHA)【美国心脏联合会】 recommend that DAT should ideally【理论上地，完美地，理想地】 be continued for 12 months beyond the date of placement【放置，安置】 in patients with a DES.20TABLE 4. Condition risk for thromboembolic eventHigher-risk condition Low-risk conditionAtrial fibrillation associated Uncomplicated orwith valvular heart disease, paroxysmal nonvalvularprosthetic valves, active atrial fibrillationcongestive heart failure, Bioprosthetic valveleft ventricular ejection Mechanical valve in thefraction35%, a history aortic positionof a thromboembolic Deep vein thrombosisevent, hypertension,diabetes mellitus, orage 75 ymitral positionBioprosthetic valveMechanical valve in anyposition and previousthromboembolic eventRecently (1 y) placedcoronary stentAcute coronary syndromeNonstented percutaneouscoronary intervention aftermyocardial infarction The risk of major embolism【栓塞，栓子】 (causing death, residual neurologic deficit【残余神经功能缺损】, or peripheral ischemia requiring surgery【外周缺血需要外科手术】) in the absence【缺少，缺乏】 of antithrombotic therapy in patients with mechanical valves is 4 per 100 patient-years.21 With antiplatelet therapy, this risk is reduced to 2.2 per 100 patient-years and with warfarin to 1 per 100 patient-years.22 In a pooled analysis of 5 randomized controlled trials【在一个集中5个随机对照试验的分析】, nonanticoagulated patients with sustained【持续的】 atrial fibrillation【心房纤颤】 had an annual stroke rate of 4.5%.23 In patients with atrial fibrillation and concomitant dilated cardiomyopathy, valvular heart disease, or recent thromboembolic events, the risk of thromboembolism is greater.24 Anticoagulation therapy for DVT is typically performed for 1 to 6 months.25 Short-term discontinuation of anticoagulation therapy does not seem to significantly increase the risk of pulmonary embolism.ELECTIVE ENDOSCOPIC PROCEDURES IN PATIENTS RECEIVING ANTITHROMBOTIC THERAPY【选择的内窥镜手术的病人接受抗凝治疗】Risk of bleeding from specific procedures while taking antithrombotic agents Diagnostic endoscopy. Although aspirin has been shown to prolong【延长】 bleeding times as long as 48 hours after ingestion【摄取】,26,27 there are no clinical trials demonstrating【证明，证实】 an increased incidence【发生率】 of bleeding in patients who have undergone【经历，承受】 upper【较高的，上面的】 or lower endoscopy with and without biopsy【组织活检】 while taking aspirin or clopidogre【氯吡格雷】l. Moreover, there is evidence【证据，迹象】 that continuing therapeutic【疗法，治疗学】 anticoagulation【抗凝】 with warfarin during the periendoscopic period【围内窥镜期】 has a low risk of bleeding in such low-risk procedures. A retrospective 【回顾的】 study by Gerson et al28 of 104 patients who underwent【经历】 171 endoscopic procedures while maintaining【保持，坚持】 therapeutic【治疗的，疗法的】 warfarin dosing found that in low-risk procedures (upper【上面的】 endoscopy【内镜检查术】 and colonoscopy【结肠镜检查】 including the use of mucosal biopsy), no clinically evident bleeding occurred【发生，出现】.28 Colonoscopic【结肠镜检查】 polypectomy【息肉切除术】. Several studies examined the risk of antithrombotic【抗血栓形成的】 therapy in postpolypectomy【息肉切除术后】 bleeding. Although 1 prospective【预期的，可能的】 study of 694 patients found a small (1%) increased risk of trace【追踪，追溯】 postpolypectomy bleeding in patients taking aspirin or NSAIDs,29 other larger retrospective【回顾的】 studies did not find this association【联想】.30,31 Because the absolute【绝对的，完全的】 risk of postpolypectomy bleeding seems to be low, even in the setting of aspirin or NSAID use, very large studies would be required to demonstrate【证明，证实】 a significantly【意义深长的，值得注目的】 elevated【升高的，高层的】 risk (if the risk was actually【确实，实际上】 increased). For example, to have an 80% power to detect a 50% increase in absolute risk of bleeding with aspirin or NSAIDs from 2% to 3%, more than 4000 patients would need to be included in each group. Thus far, there has not been a prospective study of this magnitude【巨大，重要】 conducted【引导，实施】. Although the data are limited, postpolypectomy bleeding risk seems to be increased for patients taking warfarin31,32 or resuming【重新开始】 warfarin or heparin within【在内，不超过】 1 week after polypectomy.31 Case series of prophylactic【预防性的】 clip【夹子】 application after polypectomy of small polyps【息肉】 (1 cm) in patients taking antithrombotic agents demonstrate low rates of bleeding (0%-3.3%).32-35 However, no randomized【使随机化】 controlled trials【随机对照试验】 in patients actively using antithrombotic agents have been performed【进行，完成，执行】. Because of the lack of definitive【明确的，决定性的】 clinical data and associated costs【相关成本】, routine application【常规应用】 of prophylactic mechanical【机械的】 clips or detachable【可拆开的，可分开的】 snares【可拆卸的的圈套】 in these patients cannot be recommended【推荐，建议】 at this time.Sphincterotomy【括约肌切开术】 and PEG. The overall【总的，全部的】 risk of postsphincterotomy bleeding is 0.3% to 2.0%.36-38 Withholding aspirin or NSAIDs, even as long as 7 days before sphincterotomy, does not seem to reduce the risk of bleeding.39 However, anticoagulation【抗凝作用】 with oral【口服的，口头的】 warfarin or intravenous【静脉注射】 heparin within 3 days after has been shown to increase the risk of postsphincterotomy bleeding.40 PEG placement has an overall bleeding complication【并发症】 rate of approximately 2.5%.41,42 The risk of bleeding for PEG placement【安置，放置，定位】 in the patient receiving antithrombotic therapy is unknown.Risk of stopping antithrombotic therapy before elective endoscopy When antithrombotic therapy is temporary【临时的，暂时的】, such as for DVT【深部静脉血栓形成】, elective procedures should be delayed【推迟，延期】, if possible, until anticoagulation【抗凝】 is no longer indicated【标示，表明】. This is particularly true in patients with a recently placed coronary【冠状动脉】 stent【支架】 (see detailed discussion below【请参阅下面的详细讨论】) who have significant risks of spontaneous【自发的，天然产生的】 stent occlusion【闭塞，堵塞】 with subsequent【随后的，作为结果而发生的】 acute coronary syndrome【急性冠脉综合征】 and death.43-45 If a decision is made to perform endoscopy in patients receiving antithrombotic therapy, the need to stop or reverse【交换，推翻】 these agents should be individualized【赋予个性，个别的加以考虑】. The administration【管理，施行】 of vitamin K to reverse anticoagulation for elective procedures should be avoided because it delays【延迟】 therapeutic anticoagulation【抗凝治疗】 once anticoagulants【抗凝剂】 are resumed【重新开始，继续】.46 The 2006 AHA/American College of Cardiology【心脏病学】 (ACC) guidelines recommend that in patients at low risk of thrombosis【血栓症】 (Table 4) warfarin simply be held before the procedure and that bridge therapy with heparin is usually unnecessary. The absolute【绝对的，完全的】 risk of an embolic【栓子的】 event【事件】 for patients in whom anticoagulation is interrupted for 4 to 7 days is approximately【近似的，大约】 1%.47,48 In 1 large prospective【预期的，未来的，可能的】 multicenter【多中心，多通道】 observational study, almost 1300 cases【事例】 (in 1024 patients) of warfarin interruption【中断，打断】 were examined.47 The most common indications【最常见的适应症】 for anticoagulation were atrial fibrillation (43%), venous thrombosis【静脉血栓形成】 (11%), and mechanical heart valves【瓣膜】 (10%). Only 73 patients were considered at higher risk of thromboembolism【血栓栓塞】, with 93% of the patients deemed【认为，视为】 at low risk. Only 7 (0.7%) patients had a postprocedure 【术后】 thromboembolic event within 30 days of the procedure, although more than 80% of the total study population had anticoagulation held for less than 5 days. None of the 7 patients who experienced a thromboembolic event received bridging therapy (ie, short-acting anticoagulation medication use), despite【尽管】 the fact that 2 of these patients were technically high risk 【技术风险高】because of active malignancy【主动恶化】 and recent DVT,