DIC弥漫性血管内凝血-北京协和医院血液科.

DIC的诊断与治疗北京协和医院血液科DIC的定义•DisseminatedIntravascularCoagulation•DIC是一种发生于多种疾病或特殊病理状态下，人体凝血系统被激活而引起中小血管内弥漫性微血栓形成及继发性纤溶亢进的综合征。•由于DIC发展过程中出现不同程度的血小板和凝血因子水平消耗性减少，也称之为“消耗性凝血病”或“消耗性血栓出血性疾病”。ClinicalconditionsassociatedwithDIC1.Sepsis/Severeinfection-----------44.6%2.Malignancy-------------------------20.7%–Solidtumors6.9%，AL13.8%.OccurrenceinAPL37~65%.3.Obstetricalcalamities------------13.4%–Amnioticfluidembolism,Abruptioplacentae,Deadfetus4.Trauma/Surgery-----------------7.4%5.Severehepaticfailure------------7.4%6.Vascularabnormalities–Kasabach-Merrittsyndrome，Largevascularaneurysms7.Organdestruction(e.g.,severepancreatitis)8.Severetoxicorimmunologicreactions–Snakebites，Recreationaldrugs，Transfusionreactions，TransplantrejectionMortality•DIC----DeathIsComing.•Mortalityrangesfrom31~86%,whetherornotheparinwasadministrated.•CorrelatedFactors:–Underlyingdisorders–Theextentoforgondysfuction–Thedegreeofhemostaticfailure–IncreasingageContactFactorPathwayTissueFactorPathway(IntrinsicPathway)(ExtrinsicPathway)KallikreinPrekallikrein“TissueDamage”XIIXIIaTissueFactorHKC-1InhibitorXIXIaIXCa++Ca++VIIIVIIIaIIaIIIIaVaVProteinCAPCProteinSPCInhibitorTMSKIIaIIaFibrinogenFibrinMonomerAT-IIIHCF-IIFibrinPolymerFibrinClotFDPXIIIaCa++Plasmin2AntiplasminPlasminogenUKt-PAPAI-1FibrinolysisSystemCoagulationandFibrinolysis(VIIa)XaIXaCa++PLXaXVIIaVIITFPICa++PLXIIIIIaCa++Ca++PLCa++PLTheSimplifiedMechanismofDICDIC的失调控•Sepsis、Cancer、Trauma、Obstetricalcomplications:TF•LiverDisease:AT-III、PC/PS•Sepsis:TM、PC•Pregnancy:PS•APL、AmnioticFluidEmbolism、ProstateCancer:PlasminThrombinExplosionunderPathologicalConditionsIXa(+VIII)Xa(+V)TF+VIIaThrombinFibrinogenFibrinDecreaseofAT-IIIImpairmentofPCSystemInsufficientTFPICytokines(IL-6,etc.)PlasminogenPlasminFibrinFDPsPAPAI-1GenerationofThrombinMediatedbyTFImpairmentofAnticoagulationPathwaySuppressionofFibrinolysisbyPAI-1FormationofFibrinInadequateRemovalofFibrinThrombosisofSmallandMidsizeVesselsPathogeneticPathwaysInvolvedinDICAbnormalCoagulationinDICPhysiologicAnticoagulantPathwaysDysfunctionofthePCSysteminDICSchistocytesIntravascularFibrinDIC临床表现频率•临床表现各异，根据6组报道平均发生率(WilliamsHematology-6thEdition，Table126-2)–1.出血表现：77.3%–2.肾损害：46.4%–3.呼吸道表现：42.2%–4.肝损害：39.5%–5.休克：34.5%–6.CNS表现：22.8%–7.血栓栓塞：22.2%–8.肢端苍白：6.8%–9.其它DIC的实验室检查•MarkersofThrombinGeneration–D-dimer–3Ptest–Fibrinmonomer–FibrinopeptideA–Prothrombinfragment1+2–TAT•Screeningassaysforfactorsandplateletconsumption–PT–APTT–TT–Fibrinogen–Plateletcount•Ancillarytests–FDP–ELT–AT-III–FactorV/VIII–2-AntiplasminDIC的诊断标准•根据1994年武汉全国出血与血栓学术讨论会拟订以下标准：–1.临床表现–2.实验室指标临床表现1、存在易引起DIC的基础疾病。2、有下列两项以上的临床表现–多发性出血倾向。–不易用原发病解释的微循环衰竭或休克。–多发性微血管栓塞的症状、体征，如皮肤、皮下、粘膜栓塞坏死及早期出现的肾、肺、脑等脏器功能不全。–抗凝治疗有效。实验室主要标准-同时有以下三项以上异常1.Plt.100109/L或进行性下降（肝病、白血病血小板50109/L）或有2项以上血小板活化产物升高（-TG,PF4,TXB2，GMP-140）。2.血浆Fibrinogen含量1.5g/L（白血病及其他恶性肿瘤1.8g/L，肝病1.0g/L），或进行性下降，或4g/L。3.3P(+)或血浆FDP20mg/L（肝病FDP60mg/L），或D-Dimer升高。实验室主要标准（续）4.PT时间缩短或延长3s以上或呈动态变化（肝病时PT延长5s以上）。5.周围血破碎RBC2%。•对疑难病例、需另查：1.Plasminogen含量及活性降低。2.AT-III含量及活性降低（不适用于肝病）。3.血浆因子VIII:C活性50%（肝病须具备）。DIC实验室诊断最低标准(适于基层医院)•同时有下列三项以上异常1.血小板100109/L或进行性下降。2.血浆Fibrinogen含量1.5g/L或进行性下降。3.3P阳性或血浆FDP20mg/L。4.PT缩短或延长3s以上或呈动态变化。5.周围血破碎红细胞2%。附：白血病合并DIC的实验室标准1.血小板计数低于50109/L或进行性下降，或有2项以上血浆血小板活化产物升高:-TG；PF4；TXB2；GMP-140。2.血浆Fibrinogen含量1.8g/L或进行性下降。3.3P阳性或血浆FDP20mg/L或D-Dimer水平升高。4.PT缩短或延长3s以上或呈动态变化。5.Plasminogen含量及活性降低。附：肝病合并DIC的实验室标准1.血小板50109/L或有2项以上血浆血小板活化产物升高:-TG；PF4；TXB2；GMP-140。2.血浆Fibrinogen含量1.0g/L。3.血浆FVIII:C活性50%。4.PT延长5s以上或呈动态变化。5.3P阳性或血浆FDP60mg/L或D-Dimer水平升高。慢性DIC•在转移癌、肝病、、SLE、巨大血管瘤或死胎滞留综合征等情况下，慢性持续或间歇性启动血管内凝血引发的DIC。栓塞较出血常见。•实验室：–血小板数轻度减少。–Fibrinogen正常或升高。–PT、APTT可能正常。–FDPs、D-Dimer升高。–破碎RBC常见、但程度逊于TTP者。DiagnosticalgorithmforovertDIC-ASH20021.Riskassessment:DoesthepatienthaveaunderlyingdisorderknowntobeassociatedwithovertDIC?Ifyes,proceed.Ifno,donotusethisalgorithm.2.Orderglobalcoagulationtests(plateletcount,prothrombintime[PT],fibrinogen,solublefibrinmonomers,orfibrindegradationproducts).3.Scoreglobalcoagulationtestresults:•plateletcount--------------------------------------------------------------------(100=0,100=1,50=2)•elevatedfibrin-relatedmarker(e.g.,solublefibrin----------------------monomers/fibrindegradationproducts)(noincrease=0,moderateincrease=2,strongincrease=3)•prolongedprothrombintime--------------------------------------------------(3sec.=0,3but6sec.=1,6sec.=2)•fibrinogenlevel-------------------------------------------------------------------(1.0g/L=0,1.0g/L=1)4.Calculatescore.--------------------------------------------------------------------5.If≥5:compatiblewithovertDIC;repeatscoringdaily.If5:suggestive(notaffirmative)fornon-overtDIC;repeatnext1-2days.3P(PlasmaProtamineParacoagulation)TestFgFM(FibrinMonomer)FDPThrombin肽A、BFM+FDPSPMC(SolubleProteinMonomerComplex)鱼浆蛋白FDPFM游离出来并聚集成纤维状、絮状或胶冻状PlasminELT(EuglobulinLysisTime)•血浆优球蛋白组分：由Fibrinogen,PlasminogenandPA(PlasminogenActivator)组成,不含纤溶酶抑制物。•实验程序：在PH4.5时使优球蛋白沉淀、离心去除纤溶抑制物将此沉淀溶于Buffer中加Ca++或Thrombin使其凝固37oC下观察凝块完全溶解所需时间。ELT正常值：加