影响DIC发生发展的因素

DisseminatedIntravascularCoagulation(DIC),武汉大学基础医学院病理生理学教研室李银萍2014.04,一、凝血通路(coagulationpathway）,Initiatedbytissuefactor(TF,组织因子);Canbeactivatedquickly;Primarypathwayinphysiologicalconditions.,InitiatedbyfactorSlowinactivationspeed,外源性凝血通路（ExtrinsicPathway）,内源性凝血通路（IntrinsicPathway）,正常机体凝血和抗凝血的平衡(Balancebetweencoagulationandanticoagulaiton),凝血反应的三个阶段（MainStepsofcoagulation),二、抗凝血系统(anti-coagulationsystem),Humoralanticoagulationsystem组织因子途径抑制物(tissuefactorpathwayinhibitor(TFPI)丝氨酸蛋白酶抑制物：如抗凝血酶（antithrombin，AT-)3.蛋白C系统（proteinCsystem)4.肝素(heparin)5.纤溶系统(fibrinolyticsystem),Cellularanticoagulationsystem1.Monocytes/macrophages2.Livercells3.Endothelialcells,Anti-coagulationsystem,Monocytes/macrophages：phagocytosisofactivatedcoagulationfactorsandendotoxin,etcLivercells：synthesisofanticoagulationfactorsasPC、AT，inactivatecoagulationfactorsasa、a、aEndothelialcells:,Cellularanticoagulation,Fibrinolyticsystem,纤溶酶原(plaminogen)、纤溶酶原激活物（plaminogenactivator,PA），纤溶酶原激活物抑制剂（plaminogenactivatorinhibitor,PAI）。,弥散性血管内凝血DisseminatedIntravascularCoagulation(DIC),DefinitionofDIC,DIC(DisseminatedIntravascularCoagulation,DIC）是一种由不同原因引起的以全身性血管内凝血系统活化为特征的临床综合征，因促凝物质暴露或产生增多，内源性抗凝因子及纤溶不足，导致广泛微血管内微血栓形成，同时或相继发生大量凝血因子和血小板消耗并可伴有纤溶亢进，导致多部位出血、休克、多器官功能障碍及微血管病性溶血性贫血。,DisseminatedIntravascularCoagulation(DIC)isalife-threateningacquiredsyndromecharacterizedbysystematicactivationofintravascularcoagulationarisingfromdifferentcauses.Itismanifestatedbywidespreadmicrothrombosisandsubsequenthemorrage,shock,multiorgandysfunctionandmicroangiopathichemolyticanemia,whichresultfromconsumptionandexhaustionofcoagulationfactorsandplatelets.DICcanpresentwithasimultaneouslyoccurringmicrothromboticandbleedingproblem.,Definition,EtiologyofDIC,Precipitatingcauses,Dysfunctionofmonocytes/macrophages，eg.Severeinfection,Dysfunctionofmicrocirculation,Hypercoagulatorystatus：pregnancyandacidosis,Dysfunctionoffibrinolysis,Dysfunctionofmonocytes/macrophages,Phagocytoseofmacrophage,Inabilityordecreasedabilityinremoveactivatedcoagulationfactors,Pregnancy,Hypercoagulatorystatus,MechanismsofDIC,1.Tissueinjury,releaseofTF,Causes：infection,severetrauma,surgicaloperation,necrosisoftumorcells,obstetriccomplications,initiationofDIC：hyperactivationofcoagulationsystem,MassivereleaseofTF,formaitonofTF-Fa-Facomplex,initiationofextrinsiccoagulationpathwayReleaseoflysoenzymesbyinjuriedcells，hydrolysisofactivatedcoagulationfactors,TF,Tran-membraneglycoprotein;Expressedbydamagedendothelialcells；Constitutivelyexpressedbytissues,eg.placenta,lung,liver,pancreas,brain,etc.,2.Extensivedamageofvascularendothelialcells,causes：endotoxin,virus,inflammation,hypoxia,radiation,2.Exposingofcollagen,andactivationofintrinsiccoagulationsystem,1.ReleaseofTFbyinjuriedEC,activationofextrinsiccoagulationsystem,3.increasedadhesionandactivationofplateletsinducedbycollagenandADP,ReduedTFPI,AT-,TM，PGI2,t-PA；IncreasedPAI,5.DisordersofcoagulationfactorsandanticoagulationfactorsreleasedbyEC,4.Activationofwhitebloodcellsbyinflammatoryfactorsinducedbyinfection,3.Massivedestructionofbloodcells,1)InjuryofredbloodcellsCauses：hemolysis。ReleaseofADPandphospholipid，inductionofaggregationofplateletsandcoagulation,2)ActivationandinjuryofwhitebloodcellsCauses：infection,leukemiaReleaseofTF，andintiationofextrinsiccoagulationpathway,3)Activationofplatelets,Activationofplateletsbythrombin,ADP,collagen,EffectsofcytokinesTNF、IL-1、IL-6、IL-8，etc,5.Effectsofactivatedcoagulationfactorsandplateletspositivefeedback,6.Interactionsamongcoagulationsystem/anti-coagulationsystem/kinin/inflammatoryfactors,7.DysfunctioninfibrinolysisDefectsorhyperfunction,8.Consumptionofcoagulationfactorsandplatelets,9.OxidativestressanddamagetoVEC,10.Otherthromboplasticmaterialsenteringtheblood,1)Acutepancreatitis：DirecteactivationofFandprothrombinbyTrypsin；IncreaseactivationofFandFbytrypsin;MassivereleaseofTF.2)羊水栓塞(amnioticfluidembolism)：MassivereleaseofTF；ActivationoffibrinolysisbyPA,inductionofbleeding3)EntranceoflargequantitiesofnegativelychargedmaterialsintobloodCarcinomacellsinhematogenousmetastasisParticlesasbacterials4)EntranceofexogenuoustoxinintobloodActivationofFandprothrombinbycertainapisinandvenomous,Secondaryfibrinolysis,Activationbya,a,thrombinandkallikrein,Accompaniedbyreducedactivityofcoagulation,1.Hypercoagulationstagethrombin，activationofplatelets，hypercoagulation，lowactivityoffibrinolysis，massivemicrothrombusinmicrocirculaiton2.Consumedhypocoagulationstagecoagulationfactorsandplatelets，activationofsecondaryfibrinolysis，activityofcoagulation，bleeding3.Vigoroussecondaryfibrinolysisstageplasmin，FDP；coagulationactivity，bleeding。,ClinicalstagesofDIC,Bleeding,Shock,Dysfunctionofmultipleorgans,Microangiopathichemolyticanemia,ConsequencesofDIC,Mechanismofbleeding,Coagulationsubstancesarelargelyconsumedandexhausted,particularlyfibrinogen,prothrombinandplateletsActivationofsecondaryfibrinolyticsystem,massiveFDPareproduced,Impairmentofendothelialcellsinducedbyischemia,hypoxiaandacidosissecondarytowidespreadmicrothrombus,Highpermeabilityofvascularendotheliumkinin,bradykinin,complementsandotherinflammatoryfactorsactivatedduringcoagulationprocessandfibrinolysis,DIC患者出血部位分布（%）部位百分率（%）部位百分率（%）皮肤紫癜或出血点63咯血24胃肠道出血50粘膜出血20伤口面出血46阴道出血10血尿32鼻出血9血肿26眼底出血7,2.Shock,Cardiacinsufficiencyinducedbywidespreadmicrothrombiinmicrovessels,Decreasedbloodvolumeresultingfrombleeding,Activationandreleaseofkininandbradykinincontributetodilationofmicrovessels,leadingtoincreasedvolumeofperipheralvessels.,Over50%ofacuteDICareaccompaniedbyshock,Mechanisms:,3.Multipleorgandysfunction,60%ofDICpatients,Kidneyandlungsufferthemostfrequently,Mechanisms:widespreadocclusionofmicrovesselsbymicrothrombiinducesischemia,hypoxiaoftissuecells,leadingtodisordersinmetabolism,functions.Kinin,bradykinin,complementandinflammatoryfactorsgeneratedduringonsetanddevelopmentofDICReperfusioninducedbyfibrinolysisofthrombuscanproduceoxygenfreeradical,whichmayleadtofurtherdamagetoorgans,DIC导致的常见器官功能障碍,4.microangiopathichemolyticanemia(MAHA),概念：纤维蛋白丝在微血管腔内形成网状结构，红细胞流过网孔时受到机械性损伤而破坏所导致的溶血性贫血。Schistocytes(裂体细胞）inperipheralbloodMechanisms：physicaldam