磺达肝葵钠解读.ppt

1、American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition),老年科 2012.12,ACCP9 About Fondaparinux,A first-generation synthetic analog of the antithrombin-binding pentasaccharide The prototype for most of the new indirect factor Xa inhibitors Licensed for prevention

2、of VTE in patients undergoing high-risk orthopedic surgery and, in some countries, in general surgical or medical patients A substitute for heparin or LMWH for initial treatment of VTE Licensed in Europe and Canada, but not in the United States, as an alternative to heparin or LMWH for the treatment

3、 of ACS Three of the newer indirect factor Xa inhibitors, idraparinux, idrabiotaparinux, and SR123781A,are second- and third-generation variants（变异体） of fondaparinux,Fondaparinux is given at a fixed dose of 2.5 mg daily for thromboprophylaxis and for the treatment of ACS For treatment of DVT or pulm

4、onaryembolism 5 mg : weight 100 kg. routine coagulation monitoring is not recommended patients with moderate renal insufficiency (ie, CrCl 30-50 mL/min), the dose of fondaparinux should be reduced by 50% contraindicated in patients with renal insufficiency (CrCl LMWH dabigatran/rivaroxaban (2C),LMWH

5、VKA dabigatran/rivaroxaban (2B),5.1 急性肺栓塞的抗凝方案的选择,serial imaging of the,patients with acute PE,initial treatment with parenteral anticoagulation （1B）,LMWH （2B） Fondaparinux （2C） Over UFH,LMWH Once daily Administration With the same dose （2C）,总结,预防深静脉血栓： 内科急重症+骨科手术 非骨科手术，若LDUH与LMWH禁忌，可选用 治疗静脉血栓栓塞症（深静

6、脉血栓+肺栓塞） 证据级别 2C(LMWH 2B),Thank you,3.1/3.2/3.3AF合并冠心病的抗凝治疗,ACCP 9指南 非骨科手术患者的VTE预防,CHEST 2012; 141(2)(Suppl):e227Se277S,IPC：间断充气加压装置；LDUH：低剂量普通肝素；ES：弹力袜 Roger评分：依据手术类型、麻醉评分、辅助检查等的风险评估模型 Caprini评分：依据年龄、病史、合并疾病等的风险评估模型,DVT 深静脉血栓（Deep Vein Thrombosis DVT )，DVT是在某一条深静脉中出现了血液凝块，血液的正常流动受阻。DVT通常出现在下肢，如骨盆、大

7、腿和小腿，于是把下肢DVT又分为：小腿DVT和髂股DVT 静脉血栓栓塞症（VTE）：VTE包括深静脉血栓形成（DVT）及肺栓塞（PE）,Chest 2012;141;e44S-e88S,Risk Factors for VTE in Hospitalized Medical Patients,In the Padua Prediction Score risk assessment model, high risk of VTE is defined by a cumulative score 4 points. In a prospective observational study of

8、1,180 medical inpatients, 60.3% of patients were low risk and 39.7% were high risk. Among patients who did not receive prophylaxis, VTE occurred in 11.0% of patients vs 0.3% of low-risk patients (HR, 32.0; 95% CI, 4.1-251.0). Among high-risk patients, the risk of DVT was 6.7%, nonfatal PE 3.9%, and

9、fatal PE 0.4%.,Table 11Section 2.9, 2.10, 5.6, 9.2 Risk Factors for Bleeding With and Contraindications to Use of Thrombolytic （溶栓）Therapy (Both Systemic and Locally Administered),房颤患者应用VKA与双联抗血小板的比较,达比加群较华法林的优越性,2.1.11 Recommendation Regarding Dabigatran vs Adjusted-Dose VKA Therapy: The RE-LY tria

10、l showed that dabigatran, at the higher dose of 150 mg bid, leads to reductions in nonfatal stroke, probable reductions in all-cause mortality, and no apparent increase in the risk of nonfatal major extracranial bleeding compared with VKA therapy ( Table 9 ), whereas there was no evidence that dabig

11、atran 110 mg bid leads to a significant reduction in relevant outcomes compared with VKA therapy ( Table 10 ). In the United States, the Food and Drug Administration （FDA）approved the use of dabigatran for the prevention of thromboembolism in patients with AF at a dose of 150 mg bid but not at a dos

12、e of 110 mg bid. However, the Food and Drug Administration did approve, based on pharmacokinetic considerations rather than direct evidence from RCTs in AF populations, a dose of 75 mg bid for patients with severe renal insufficiency (defined as a creatinine clearance 15-30 mL/min).,3.1 Patients Wit

13、h AF and Stable Coronary Artery Disease,3.1. For patients with AF and stable coronary artery disease and who choose oral anticoagulation, we suggest adjusted-dose VKA therapy alone (target international normalized ratio INR range, 2.0-3.0) rather than the combination of adjusted-dose VKA therapy and

14、 aspirin (Grade 2C) . stable coronary artery disease : no acute coronary syndrome within the previous year,4.1 Patients Undergoing Elective Cardioversion of AF（48h）,serial imaging of the,patients with AF of greater than 48 h or unknown duration,undergoing elective electrical or pharmacologic cardiov

15、ersion,Anticoagulation at least 3 weeks before （1B),Anticoagulation at least 4 weeks after (1B) regardless of the baseline risk of stroke,4.1.2 Patients Undergoing Elective Cardioversion of AF（48h）,serial imaging of the,patients with AF of documented duration of 48 h or less,undergoing elective elec

16、trical or pharmacologic cardioversion,anticoagulation at presentation and proceeding to cardioversion （2C),Anticoagulation at least 4 weeks after (2C) regardless of the baseline risk of stroke,4.2 Patients Undergoing Urgent Cardioversion for Hemodynamically Unstable AF,serial imaging of the,AF patie

17、nts and hemodynamic instability,undergoing urgent cardioversion,therapeutic-dose parenteral anticoagulation before （2C) if possible,Anticoagulation at least 4 weeks after (2C) regardless of the baseline risk of stroke,治疗剂量：Enoxaparin 1 mg/kg bid or 1.5 mg/kg daily prophylactic-dose：enoxaparin 30 mg

18、bid or 40 mg daily An intermediate-dose regimen ：for bridging and is intermediate in anticoagulant intensity between high- and low-dose regimens (eg, enoxaparin 40 mg bid),传统凝血模式分为内源性及外源性凝血途径,内源性(接触因子)途径,外源性(组织因子)途径,XIa,XIIa,IXa,Xa,IIa,VIIIa,Va,VIIa,组织因子,纤维蛋白原,纤维蛋白,激活,激活,激活,激活,激活,激活,Dunn CJ, et al.

19、Drugs. 2000(60) 1: 203-237,三大抗凝体系,外源性凝血途径,XIa,IXa,Xa,IIa,VIIIa,Va,纤维蛋白原,纤维蛋白,XIIa,接触性血栓途径,激活,激活,激活,激活,激活,VIIa,组织因子,Alban S. Current Pharmaceutical Design.2008;14: 1152-1175,组织因子 途径抑制物,抗凝血酶III,蛋白C/蛋白S,肝素类、戊糖及水蛭素抗凝作用位点,VIIa,Va,XIa,IXa,Xa,IIa,VIIIa,激活,激活,激活,激活,激活,Mackman N. NATURE.2008; 451: 914-918,组织因子,普通肝素 低分子肝素,水蛭素,磺达肝癸钠,纤维蛋白原,纤维蛋白,XIIa,肝素类抗凝药物抗凝机制,外源性凝血途