冯正义-ECMO-抗凝及凝血

ECMO中的抗凝阜外医院体外循环科冯正义ECMO为何要抗凝抗凝剂抗凝监测ECMO出血及栓塞（一）ECMO为何需要抗凝生理凝血抗凝动态平衡凝血系统凝血因子血小板抗凝血系统体液抗凝（肝素ATⅢ）蛋白C系统纤溶系统细胞吞噬血液流速内皮细胞阻隔作用分泌功能调控作用血液流动性防血液接触促抗凝平衡MOPumpCPBECMOECMO与CPB对血液影响单位时间内血液与非内皮人工材料接触强度血液暴露于生物材料的时间创面或损伤的大小肝素用量的大小ECMOCPBSurface/X-Coating减少血液与异物的接触减轻血小板、WBC、补体的激活长时间、闭式、部分CPB过程ECMO最大的敌人：血液与非生理的人工材料接触ECMO启动凝血瀑布•ECMO开始意味着血液与异物表面接触反应开始•内源凝血途经激活的同时，“外源性凝血途径”启动新的促凝和抗凝血平衡Top3:1.Bleeding/thrombsis32%2.Infection17%3.Oxygenatorplasmaleakage/hemolysis16%ECMOcomplications20161675444171512BleedingoxygenatorplasmaleakageHemolysisOxygenatorchangeGastrointestinalhemorrhageBraininjuryMSOFDICInfectionRenaldysfunctionClotsincircuit抗凝—ECMO成功的第一步阜外医院2004-2010年ECMO资料目标是预防临床中由于血液与大量的异物表面接触而形成血栓,维持促、抗凝动态平衡。抗凝个体化原则。明确ECMO中血栓形成的同时伴有凝血因子的消耗。明确凝血因子\血小板在抗凝治疗中的角色。ECMO中抗凝理念（二）抗凝剂肝素肝素:ECMO中主要抗凝剂ATlll（antithrombinlll）.与ATlll结合,通过抑制factorX(Xa)激活和Prothrombin转化为thrombin.从而阻止血栓形成硫酸粘多糖带负电荷半衰期30-45分钟分子量3,000-30,000从牛肺或猪肠粘膜中提取不能终止已经发生的凝血反应!!因此肝素用于预防凝血。易被鱼精蛋白中和。肝素特性Heparin–Half-lifeandUnitsHalf-lifedependsontheamountadministered.100units/kg=1hour400units/kg=2.5hours800units/kg=5hours肝素管理持续泵肝素稳定后测ACT/3小时禁止单剂量单次给药肝素加减：根据ACT、APTT，出血的情况初始剂量：（ecmosetup)100U/kgbolus维持剂量：范围:ACT160-200秒速度:10-60u/Kg/hr每天配制新的肝素泵Heparinpracticalities(1)50-100u/KgatcannulationMonitorACTfrequently-30minutely(fromIAline)StartHeparininfusionat20u/Kg/HrwhenACT200sAim:ACT160-180(differentnormalswithdifferentmachine)Dependsonbleedingrisk/clottingriskEvery1-2hrswhenstableHighACTDecreasedoseby10-20%?Don’tstoptheheparinLowACTIncreasedoseby10-20%?Don’tgiveabolusHeparinpracticalities(2)Factorsincreasingtheneedforheparin–Platelettransfusion/Thrombocytosis–HighUrineoutput–Heparinresistance–ATIIIdeficiencyFactorsdecreasingtheneedforheparin–Renalfailure–ThrombocytopeniaKeepplatelets100000个体化原则（1）-不同病情每个患者对相同剂量的肝素反应不一样。1、CPB与非CPB患者2、距离CPB后时间3、不同年龄：婴幼儿4、肝、肾功能不全延长肝素作用6、尿量的排出对ACT影响很大，个体化原则（2）-ATlll缺乏危重新生儿循环血中ATlll常常低下。长时间CPB患者。肝功能低下。伴有心脏粘液瘤者。预充FFP，补充ATIII其他抗凝剂-肝素替代品比伐如定(bivalirudin)阿库曲班(argatroban)水蛭素(hirudin)ArtifOrgans.2007Jun;31(6):461-5.ArgatrobaninECMOAnnThoracSurg,2007May;83(5):1865-7SuccessfuluseofbivalirudinforECMOinapatientwithHITbolus:0.5mg/kg,continuosinfusion0.25-1mg/kg/h,ACT200s±continuosinfusion2-0.2microg/kg/min,aPPT50-60s（三）抗凝监测ACT监测ACT：维持160-200s监测仪器尽量选用进口ACT仪关于HEMOCHRONJr.ACT+:血肝素浓度1.0-6.0U/ml，有较好的线性关系。ACT-LR:对低肝素浓度敏感。ACT’s异常ACT缩短检查输注肝素的管路、三通是否通畅ATIII水平???Heparin药效下降尿排出多ACT’s过度延长验证监测技术是否有误确认没有额外肝素进入血液稀释低温DICHITFg浓度ATIII活性XII活性温度PLT数量及功能ACT肝素浓度与ACT值非线性相关常规检测ACT局限性影响ACT因素RedcellvolumePlateletcountPlateletfunctionCalciumTemperatureHeparinAntithrombinIIIPlasminogenMonocytesTissuefactorProteinCpHActivatingagentPrekallikrienHighMWkininogenFactorXIIFactorXIFactorIXFactorVIIProthrombinFibrinogenFactorVIIIonicstrengthHistidine-richglycoproteinPlateletfactor4AprotininACT﹠APTTACT反映全血中各个凝血因子及血小板凝血状态的综合程度，是一种监测肝素抗凝效果的粗略手段，实用、简便可行检测仪器或方法有差别APTT反映因子Ⅰ、Ⅱ、Ⅴ、Ⅷ、Ⅸ、Ⅹ、Ⅺ和Ⅻ的活性，正常值31s，ECMO中维持60-80s。它检测内源性凝血通路/共同通路，对是否补充凝血因子有指导意义，对小剂量(0.1-1u/ml)肝素比较敏感，ECMO中有较大帮助。AntiXaAntiXaassayisthemostspecificmethodofmeasuringheparineffectthatwehaveavailable–Therapeutic0.25–0.5u/ml–Alsotheonlywaytomonitorlowmolecularweightheparin(0.4–1u/ml)HeparinmonitoringACTTEGAPTTAntiXaPriceCheapExpensiveMoreexpVexpSiteBedsideBedsideLab，BedsideLabSampleWholebloodWholebloodPlasmaPlasmaMeasuresWholebloodclottingWholebloodclottingIntrinsicandcommonpathwaysHeparinactivity(indirect)血栓弹力图(TEG)---鉴别凝血紊乱和外科性出血;凝血因子缺乏与血小板功能障碍;区分自身凝血功能障碍与抗凝药物影响.工作原理测试杯震动杯盖和悬垂丝附着在一起血块使杯子和盖耦合在一起杯盖的运动就是反应血块的强度系统将检测到凝血开始到纤溶原始的物理信息进行分析常见参数及意义：探针旋转振幅时间凝血因子纤维蛋白原血小板聚集功能纤维蛋白溶解TEG参数:R反应时间(4–8min*)*Version4.2normalvaluesdefaultTEG参数:K和Angle()血块形成速率RClottimeIIagenerationFibrinformationCoagulationpathwaysRClottimeIIagenerationFibrinformationCoagulationpathwaysParameterHemostaticActivityHemostaticComponentHypo-coagulableHyper-coagulableR(min)R(min)R(min)R(min)K(min)(deg)K(min)(deg)K(min)(deg)K(min)(deg)ClotrateFibrinmeshFibrinplateletCoagpathwaysplateletsKClotrateFibrinmeshFibrinplateletCoagpathwaysplateletsKDysfunction4-8min:Angle(47-74°)K:血块动力学(0-4min)TEG参数:MA最大血块强度RClottimeIIagenerationFibrinformationCoagulationpathwaysRClottimeIIagenerationFibrinformationCoagulationpathwaysParameterHemostaticActivityHemostaticComponentHypo-coagulableHyper-coagulableR(min)R(min)R(min)R(min)K(min)(deg)K(min)(deg)K(min)(deg)K(min)(deg)MAMAMAMAClotrateFibrinX-linkingFibrinplateletCoagpathwaysplateletsKClotrateFibrinX-linkingFibrinplateletCoagpathwaysplateletsKMaximumclotstrengthPlatelet–fibrininteractionsPlatelets(~80%)Fibrin(~20%)MAMaximumclotstrengthPlatelet–fibrininteractionsPlatelets(~80%)Fibrin(~20%)MADysfunction最大振幅(54–72mm)TEG参数:LY30与EPL血块消融RClottimeIIagenerationFibrinformationCoagulationpathwaysRClottimeIIagenerationFibrinformationCoagulationpathwaysParameterHemostaticActivityHemostaticComponentHypo-coagulableHyper-coagulableR(min)R(min)R(min)R(min)K(min)(deg)K(min)(deg)K(min)(deg)K(min)(deg)MAMAMAMACl