磺達(dá)肝葵鈉解讀課件

1、American College of Chest Physicians Evidence-BasedClinical Practice Guidelines(9th Edition) 老年科2012.12 ACCP9 About FondaparinuxA first-generation synthetic analog of the antithrombin-binding pentasaccharideThe prototype for most of the new indirect factor Xa inhibitorsLicensed for prevention of VTE

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

3、Three of the newer indirect factor Xa inhibitors, idraparinux, idrabiotaparinux, and SR123781A,are second- and third-generation variants（變異體） of fondaparinuxFondaparinux is given at a fixed dose of 2.5 mg daily for thromboprophylaxis and for the treatment of ACSFor treatment of DVT or pulmonaryembol

4、ism 5 mg : weight 100 kg.routine coagulation monitoring is not recommendedpatients 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) LMWHVKA dabigatran

5、/rivaroxaban(2B) 總結(jié)預(yù)防深靜脈血栓： 內(nèi)科急重癥+骨科手術(shù) 非骨科手術(shù)，若LDUH與LMWH禁忌，可選用治療靜脈血栓栓塞癥（深靜脈血栓+肺栓塞） 證據(jù)級別 2C(LMWH 2B) Thank you ACCP 9指南 非骨科手術(shù)患者的VTE預(yù)防VTE風(fēng)險(xiǎn)分級VTE發(fā)生率Roger評分*Caprini評分*出血風(fēng)險(xiǎn)預(yù)防推薦推薦級別極低危0.5%1034低LMWHLDUH機(jī)械預(yù)防（IPC）2 B2 B2 C高機(jī)械預(yù)防（IPC）2 C高危6.0%5低LMWHLDUH建議聯(lián)用機(jī)械預(yù)防（ES或IPC）1 B1 B2 C高機(jī)械預(yù)防（IPC）2 CCHEST 2012; 141(2)(Su

6、ppl):e227Se277SIPC：間斷充氣加壓裝置；LDUH：低劑量普通肝素；ES：彈力襪Roger評分：依據(jù)手術(shù)類型、麻醉評分、輔助檢查等的風(fēng)險(xiǎn)評估模型Caprini評分：依據(jù)年齡、病史、合并疾病等的風(fēng)險(xiǎn)評估模型DVT 深靜脈血栓（Deep Vein Thrombosis DVT )，DVT是在某一條深靜脈中出現(xiàn)了血液凝塊，血液的正常流動(dòng)受阻。DVT通常出現(xiàn)在下肢，如骨盆、大腿和小腿，于是把下肢DVT又分為：小腿DVT和髂股DVT靜脈血栓栓塞癥（VTE）：VTE包括深靜脈血栓形成（DVT）及肺栓塞（PE）Xa因子磷脂Va因子Xa因子Ca2+內(nèi)源性通路外源性通路凝血酶原凝血酶纖維蛋白原纖維

7、蛋白凝血酶原復(fù)合物啟動(dòng)階段放大階段血小板聚集凝結(jié)Xa因子直接Xa因子抑制劑Chest 2012;141;e44S-e88SRisk Factors for VTE in Hospitalized Medical PatientsIn 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 1,180 medical inpatients, 60.3% o

8、f patients were low risk and 39.7% were high risk. Among patients who did notreceive 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%, andfatal PE 0.4%.Table 11Section 2.9,

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)房顫患者應(yīng)用VKA與雙聯(lián)抗血小板的比較達(dá)比加群較華法林的優(yōu)越性2.1.11 Recommendation Regarding Dabigatran vs Adjusted-Dose VKA Therapy: The RE-LY trial showed that dabigatran, at the higher

10、 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 dabigatran 110 mg bid leads to a significant

11、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 dose of 110 mg bid.However, the Food and Dr

12、ug 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). 4.1 Patients Undergoing Elective Cardioversion of AF（48h）

13、serial imaging of thepatients with AF of greater than 48 h or unknown durationundergoing elective electrical or pharmacologic cardioversionAnticoagulation 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 Electi

14、ve Cardioversion of AF（48h）serial imaging of the patients with AF of documented duration of 48 h or lessundergoing elective electrical or pharmacologic cardioversionanticoagulation at presentation and proceeding to cardioversion （2C)Anticoagulation at least 4 weeks after (2C)regardless of the baseli

15、ne risk of stroke 4.2 Patients Undergoing Urgent Cardioversion for Hemodynamically Unstable AFserial imaging of the AF patients and hemodynamic instability undergoing urgent cardioversiontherapeutic-dose parenteral anticoagulation before （2C) if possibleAnticoagulation at least 4 weeks after (2C)reg

16、ardless of the baseline risk of stroke 治療劑量：Enoxaparin 1 mg/kg bid or 1.5 mg/kg dailyprophylactic-dose：enoxaparin 30 mg bid or 40 mg dailyAn intermediate-dose regimen ：for bridging and is intermediate in anticoagulant intensity between high- and low-dose regimens (eg, enoxaparin 40 mg bid)傳統(tǒng)凝血模式分為內(nèi)源

17、性及外源性凝血途徑 內(nèi)源性(接觸因子)途徑外源性(組織因子)途徑XIaXIIaIXaXaIIaVIIIaVaVIIa組織因子纖維蛋白原纖維蛋白激活激活激活激活激活激活Dunn CJ, et al. Drugs. 2000(60) 1: 203-237三大抗凝體系外源性凝血途徑XIaIXaXaIIaVIIIaVa纖維蛋白原纖維蛋白XIIa接觸性血栓途徑激活激活激活激活激活VIIa組織因子Alban S. Current Pharmaceutical Design.2008;14: 1152-1175組織因子途徑抑制物抗凝血酶III蛋白C/蛋白S肝素類、戊糖及水蛭素抗凝作用位點(diǎn)VIIaVaXIaI

18、XaXaIIaVIIIa激活激活激活激活激活Mackman N. NATURE.2008; 451: 914-918組織因子普通肝素低分子肝素 水蛭素 磺達(dá)肝癸鈉 纖維蛋白原纖維蛋白XIIa肝素類抗凝藥物抗凝機(jī)制外源性凝血途徑XIaIXaXaIIa纖維蛋白原纖維蛋白接觸性血栓途徑XIIa激活激活激活激活激活激活VIIaDouglas B.Cines.Chest 1986;89;420-426肝素組織因子抗凝血酶III分子量5400以上才具有抗IIa活性Alban S. Current Pharmaceutical Design.2008;14: 1152-1175Canales JF, et al. Am J Cardiovasc Drugs. 2008;8(1):15-25肝素必須與AT及IIa分子結(jié)合才能發(fā)揮抗IIa作用, 為分子鏈長度依賴性XaAT肝素分子鏈IIaAT肝素分子鏈抗IIa示意圖抗Xa示意圖肝素