ECMO的抗凝管理-ELSO培训

1、ECMO的抗凝管理ECMO抗凝管理. i$ELSOiill| .郭震上海交通大学附属胸科医院ECMO的管理凝血与抗凝抗凝监测血栓与出血案例分析中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝管理决定成败中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理中国生物医

2、学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理ECMO complications(Bleeding) oxygenator plasma leakageHemolysisH Oxygenatorchange Qstrointestinal hemorrhageH Brain injuryB MSOFAH InfectionB Renal dysfunctionfM

3、CIots in circuit抗凝管理决定成败Adult Respiratory ComplicationsMechanical: Clots: oxygenator Mechanical: Clots: bridge Mechanical: Clots: bladder Mechanical: Clots: hemofilter Mechanical: Clots: otherHemorrhagic: Gl hemorrhageHemorrhagic: Cannulation site bleedingHemorrhagic: Surgical site bleedingHemorrhag

4、ic: Hemolysis (hgb 50 mg/dl)Hemorrhagic: Disseminated intravascular coagulation (DIC)Neurologic: CNS infarction by US/CTNo.Reported% ReporteaNo. Survived%Survived67912.9%37455%851.6%4856%881.7%5057%1442.7%6344%3396.4%19156%2935.6%10034%79515.1%40451%71713.6%31143%3186.0%11737%1763.3%4827%1062.0%3230

5、%2063.9%4120%International Summary January, 2014Neurologic: CNS hemorrhage by US/CT抗凝管理决定成败Mechanical: Clots: oxygenatorMechanical: Clots: bridgeMechanical: Clots: bladderMechanical: Clots: hemofilterMechanical; Clots: otherHemorrhagic: Gl hemorrhageHemorrhagic; Cannulation site bleedingHemorrhagic:

6、 Surgical site bleedingHemorrhagic: Hemolysis (hgb 50 mg/dl)Hemorrhagic: Disseminated intravascular coagulation (DIC) Neurologic: CNS infarction by US/CTNo.%No.%ReportedReportedSurvivedSurvived4239.6%17241%410.9%2356%110.2%545%731.7%1825%2876.5%10938%1774.0%4324%87219.8%35741%1,01323.0%34834%3137.1%

7、9530%1804.1%4424%1693.8%3822%962.2%88%International Summary January, 2014Neurologic: CNS hemorrhage by US/CT中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理并发症:出血和血栓III中国生物医学工程学会体夕卜循环分会Chinese Society of

8、Extra-Corporeal CirculationECMO的抗凝管理中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理并发症:出血和血栓III中国生物医学工程学会体夕卜循环分会Chinese Society of

9、Extra-Corporeal CirculationECMO的抗凝管理凝血与抗凝的平衡血栓调理蛋白(TM)激活蛋白C生成APC,灭FVa, FVIIIa组织因子途径抑制物抑制TF-FIX复合物类肝素物质有浓集ATJII在内皮表面的作用，后者中和丘血及E漩 一氧化氮(NO)进入平滑肌细胞激活cGMP血管扩张，抑制平滑肌收缩，抑制血小板,单核细胞，中性粒细胞与内皮粘附抑制血小板聚集凝血与抗凝的平衡中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理中国生物医学工程学会体夕卜循环分会Chinese Soci

10、ety of Extra-Corporeal CirculationECMO的抗凝管理ThrombosisConsumption of Coagulation FactorsActivation of FibrinolysisAnficoaulation Massive Transfusion Platalet ConsumptionPlotalat Activation and AdhasiorActivation of Coagulation Factoir nLaiLjkocyta and Complemant Activation 1Exposur to non - andotha 1

11、 ial call sur*facasAnticoagulationThrombosisHemorrhage中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理砸UU垦HiG12Hageman 因子11血浆凝血激酶前质9血浆凝血激酶成分8抗血友病因子7稳定因子3组织因子10stuart因子5易变因子4钙2凝血酶原1纤维蛋白原中国生物医学工程学会体夕卜循环分会Ch

12、inese Society of Extra-Corporeal CirculationECMO的抗凝管理EC MO为什么抗凝?异物表面接触内源凝血途经激活的同时II IkIH外源性凝血途径启动并加强 肝素不能完全阻止疑血 管道表面的预处理（涂期II 减少凝血的启动卩幺:庆庆接触时间和面积表面负电荷是否有创面血流模式和剪切力表面对蛋白的吸附内壁光滑程度持续缺血、缺氧严重感染内毒素储血罐多脏器功能衰竭se Society of Extra-Corporeal CirculationECMO的抗凝管理生物相容性材料Coating AgentTrade NameManufacturerPoly-2-

13、methoxyla ciylateX CoatingTerumoSi/caprolactam copolymerSMARxTCobe/Sorinhepariu + Recombinant human albumin.BiolineMaquetSynthetic albuminSafelineMaquetbiopassive polymer”SoftlineMaquethepariu.CarniedaMedtronichepariu 十 sulphonated polymersTriliumMedtronicHeparinDuraflo IIBaxter生物相容性材料PHOSPHORYLCHOL

14、INE COATINGPMP Polymethylpentene：聚甲基戊烯 PP Polypropylene：聚丙烯肝素的管理:中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理易被鱼精蛋白中和肝素的个例 HIT与肝功能夭肝素诱导白f20u/Kg/hr|单链寡糖组成的多聚粘多糖链，1000030000D通过与AT III结合起效抑制内源性和共同途径不能终止已经发

15、生的凝血反应i 插管前50-100- u/Kg 当ACTQT- t Associated TlirombosV1AnHcoagulank MonitoringMetabolismHalf-lifeCommentlepirudin水蛭素/( B&m, Q.4 mg/kgfc / inhial infusion rate, 0,15 mg kg-1 h1 J15-2-5 x baseline aPTTRenalSQ mmRehtivly centra indictin renalfailure risk of aftaphylaxis especially on reexposure; minor

16、 prolongation of INRBivlirudin比伐如定1No bvlus; initial infusionMte 0.15-0201lUg 呛7.h-L1.5-Z5 X baseline aPTTknzymic (80?4);Rensil (20%)25 minSmall experience in treating HIT; manor prolongation of INRArgnilrobn阿库曲班 No bolus： initiM infusion/ 制匕2档/ * min1/i430 x baMlJne a PIT4Q-5Q minInitial iosu? 0.5

17、g- kg1* - Min1 in heps tic instjffickncy； mockr* to marked prolongation of INR (complicates uarFarin overlap)、Identical pfoszols吵& isolated HIT, excopt for lpirudin no initial bolus； iinitijl infusion 儿也 0.10 叫j 畑 h 1 Jidjusted io jPTT l.E-2.5 X baselineIo the package insert and in order t -avoid ov

18、erdosing (wpedally in elderly patients with unrecognizedrenal dyiunciion w rccomnniend omitting the lepirudin bolus unless there is life threatening ihrombosis. h Generally the patients byline aPTT should bv(wh-cn /ipplibM for Cileuliting Wrgvt mngv, whyn ipprppritr； othyrvdY, th窗 min of thv htworot

19、ory rtormiil G)ng i*in bfiied. c Subnii.11 97% ACT 82% ATHI活度 65% Anti-Xa范围不一 43% TEGVariability in Anticoagulation Management of Patients on Extracorporeal Membrane Oxygenation: An In ternational Survey*Melania M. Bembea, MIX MPHU; Gail Annich MIP; Peter Rycus. MPH4; Gary Oldenburg1;Ivor Berkowitz,

20、Peter Pronovost, Ml), Phi)1Pediatric Critical Caro McdtcincFebruary 2013 Vdumo 14 Number 2Boston Children Phoenix ChildrensaPTT60-80 sec60-80 secPTv 17 secFibrinogen 100 mg/dL100 mg/dLAnti Xa0.30 - 0.70 IU/mL0.3-0.7 U/mLAntiThrombin70%50%ACT180-220160-180 if bleeding中国生物医学工程学会体外循环分会Chinese Society o

21、f Extra-Corporeal Circulation抗凝的监测 ACT： 180220s Prekallikrien High MW kininogen Factor XII Factor XI Factor IX factor VII Frothrombin F brinogen Factor VII Ionic strength Histidine-rich glycoprotein Platelet factor 4 Aprotinin Red cell volume Platelet count Platelet function Calcium Temperature Hepa

22、rin Antithrombin III Plasminogen Monocytes Tissue factor Protein C Activating agentiese Society of Extra-Corporeal Circulation ACT缩短检查肝素泵管路三通是否通畅 ATIII水平肝素药效下降尿排出多肝素效价 ACT过度延长额外肝素进入血液稀释低温 DIC HIT感染inese Society of Extra-Corporeal Circulation中国生物医学工程学会体外循环分会ECMO的抗凝管理抗凝的监测 APTT反映因子I、II、V、Vffl、IX、X、XI和

23、刈的活性 正常值31s , ECMO中维持50-80s , Bxl.52g检测内源性凝血通路/共同通路对/剂量(0.1 -1 u/ml)肝素比较敏感与肝素剂量相关性较好对ECMO中抗凝监测有较大帮助婴幼儿偏长，误差较大 监测频率:once/4h 24h中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的监测中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的监测 Anti-X反映I正常彳 ECM无法丿

24、价格?监测扌中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的监测Anti-Xa (0.3 0.8 u/ ml)aPTT (60- 90 seconds)ACT (180-220 seconds)RcsponsenormalTTRepeat anti factor Xa, aPTT, ACTCorisider flbiiii degiadatioii/split products to rule out DIC Check patiejit teiijeiatmeRule out hcmodil

25、utionIf at upper end of anti factor Xa raiige3 consider decreasing UFH chip rate by 5-10%.normal4-1Consider checking ATL111 and Fibrinogen levelAdminister FFP 20ml/K_g or ATIII, then repeat anti factor Xa levelIncrease LJFH drip rate by 10%normalT1Consider checking ATIII levelRepeat aiitifactoi Xa a

26、PTT and ACT at this time If at upper end of antiiactor Xa range；, consider decreasing.LJFH drip rate by 5-1 0%.ttTDecrease UFH chip rate by 10%TI-lConsider checking ATIII level Adniiiiister FFP/AT111 (preferably ATI I)Decrease UFH drip rate by 5-10%XJ-XConsider UFH bolusIncrease UFH drip late by 10%

27、It1Consider UFH bolusConsider fibrin degradatioji/spMt products to rule out LC In orca so UFH drip rate byJ Extra Corpor Technol. 2014 Mar;46(l):69-76.Comparison of routine laboratory measures of heparin anticoagulation for neonates on extracorporeal membrane oxygenation.中国生物医学工程学会体夕卜循环分会Chinese Soc

28、iety of Extra-Corporeal CirculationECMO的抗凝管理抗凝的监测PTD-Dimer2TEG An alysis中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的监测血栓弹力图（TEG）鉴别凝血紊SLW外科性出血凝血因子缺乏与血/皈功能障碍区分自身凝血功能障不彌抗凝药物影响中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的监测中国生物医学工程学会体夕卜循环分会Chi

29、nese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的监测中国生物医学工程学会体夕卜循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的监测 ACT： 180 220s简单、粗略、易变、普及 APTT： NX 1.52倍，5080s没有一种手段可以准确反映肝素抗凝状态依赖多种监测手段的联合应用 ATIII activity： 50-70%, 0.5u/ml TEG、Sonoclotx ROTEM:全面但不便，出血的管理中国生物医学工程学会体夕卜循环分会Chinese

30、Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的管理保护凝血机制涂层管道凝血成分的维持中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的管理FFP、PLT、冷沉淀、血浆抗纤溶药物:6-氨基己酸、氨甲环酸PLT 5080X 109/L, FIB 1.0g/L明显出血或出血高危者，FIB 1.5g/L, ACT-140-180秒充分外科止血小量出血绝不可忽视避免不必要的有创操作保护呼吸道、消化道、尿道不易发现的出血：脑、消化道、胸腔抗凝永远达不到生理

31、状态中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的管理中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的管理即使在出血时，千万不要忘记抗凝！ !中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的管理中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal C

32、irculationECMO的抗凝管理抗凝的管理血流速度慢离心泵、接头、心脏腔室中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的管理充分抗凝、心脏跳动、左心引流左右心房、静脉插管尖端中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的管理渗血抗凝的管理一DIC凝血后继发出血，高凝到低凝过程大量微栓和出血并存微循环障碍，内环境突然恶化器官功能障碍：肝功能、指端发黑变凉等膜肺氧合功能下降出血（凝血因子消耗

33、和继发纤溶） ACT异常延长与肝素无关皮肤出血点或瘀斑 ECMO中一旦发生死亡率相当高降低ACT，减肝素，鱼精蛋白拮抗?凝血指标和功能检查，判断原因 新鲜冰冻血浆（10ml/kg/次量） 如果没有效果，给予冷沉淀纤维蛋白原150mg/dl. PLT血小板计数8X109/L vn因子如渗血任仍然不止，考虑检查D-二聚体，FDP、TEG, ATIII,肝素水平，肝素抗体试验（排除HIT）中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理抗凝的管理HIT中国生物医学工程学会体外循环分会Chinese Soci

34、ety of Extra-Corporeal CirculationECMO的抗凝管理抗凝的管理HITPlatelet removal by splenic macrophagesRelease of procoagulant microDarticleslx船rThrombosis/Aggregation PF4PLCy2SykADPPlatelet;yiPLCy27 FcyRIIAHepari n/PF4?JHepari n-PF4 immune complexigGFcyRIIAProcoagula nt platelet-derived microparticlesVessel wall中国生物医学工程学会体外循环分会Chinese Society of Extra-Corporeal CirculationECMO的抗凝管理病例讨论 60kg,男性，ARDS VV-ECMO辅助第四天血流动力学稳定，血气