臨床血液學(xué)檢驗(yàn)：血栓與止血基礎(chǔ)理論

血栓與止血基礎(chǔ)理論

ThrombosisandHaemostasisBleedingPurpura（Dermatorrhagia）DermatorrhagiaHemostasisAnticoagulation正常凝血-抗凝平衡凝血低下，抗凝增強(qiáng)出血HemostasisAnticoagulation凝血亢進(jìn)，抗凝減弱血栓HemostasisAnticoagulationHemostasisAnticoagulation正常凝血-抗凝平衡Primaryhemostasis初期止血血液凝固系統(tǒng)抗凝血系統(tǒng)纖維蛋白溶解系統(tǒng)血液流變特性血栓形成

第一節(jié)、血管壁的止血作用◆血管壁的結(jié)構(gòu)了解◆血管的止血作用熟悉第二節(jié)、血小板的止血作用◆血小板的結(jié)構(gòu)熟悉◆血小板的活化了解◆血小板的止血功能掌握Primaryhemostasis初期止血血液凝固系統(tǒng)抗凝血系統(tǒng)纖維蛋白溶解系統(tǒng)血液流變特性血栓形成

primaryhemostasisvesselwallsystemplateletsystemvesselwall

vWF\t-PA,PAIFn\TSP\凝血因子Tunicaintima

基底膜、膠原、平滑肌、微纖維彈力纖維TunicamediaTunicaadventitiaVesselwallhemostasisVasoconstrictionPlateletactivationCoagulationpathwayAnticoagulantbalanceandremodelling1.血小板結(jié)構(gòu)⑴表面結(jié)構(gòu)⑵骨架系統(tǒng)和收縮蛋白⑶細(xì)胞器和內(nèi)容物

⑷特殊膜系統(tǒng)⒉血小板活化⒊血小板功能

⑴PeripheralZone

PlasmaMembrane–BilayeredLipidsMembraneproteins

PF3PS膽固醇糖脂磷脂鞘磷脂甘油磷脂

---磷脂酰膽堿PC、磷脂酰乙醇胺PE

磷脂酰絲氨酸PS、磷脂酰肌醇等PLTPlasmaMembrane:LipidsGlycoproteinGPIb-IX---

vWFreceptor,adhesion

GPⅡb-Ⅲa---Fgreceptor

,aggregationvWF、Fn

receptor,adhesionGPIa-IIa----collogenreceptorGPIc-IIa----FnreceptorGPIV----TSPreceptorGPV----thrombinreceptorGMP-140：regulateplateletandendothelialcellGPIa、Ib、IIb、IIIa（被ICSH統(tǒng)一命名）GPIb/IXvWFGPIIb/IIIaFibrinogen

vWF、FnGPIa/IIaCollagenGPIc/IIaFnGPVThrombinGPIVTSP

1.血小板結(jié)構(gòu)⑴表面結(jié)構(gòu)⑵骨架系統(tǒng)和收縮蛋白⑶細(xì)胞器和內(nèi)容物

⑷特殊膜系統(tǒng)⒉血小板活化⒊血小板功能◆膜脂質(zhì)◆膜蛋白⑵Sol-GelZonePLTCytoskeletonMicrotubulesPLTdiscoidshapeMicrofilamentsSubmembranefilaments1.血小板結(jié)構(gòu)⑴表面結(jié)構(gòu)⑵骨架系統(tǒng)和收縮蛋白⑶細(xì)胞器和內(nèi)容物

⑷特殊膜系統(tǒng)⒉血小板活化⒊血小板功能◆微管◆微絲◆膜下細(xì)絲⑶Organelle-ZoneCytoplasmiccontentAnucleateFewmitochondriaGranules

Alpha:?-TG、PF4、TSP、FV、Fg、FXI、GMP-140、FnDenseLysosomes

mitochondria

peroxisomesPLTGranules’Content

GranuleFunctionAlphaThromboglobulinPF4PDGFFibrinogen,FactorsV&VIIIvWFPlasminogena1-antiplasminHMWKFibronectinInhibitheparin;vesselrepairInhibitheparinVesselrepairFibrinformationPLTAdhesionPrecursorofplasmin(fibrinolysis)PlasmininhibitorContactactivation:intrinsiccoagulationpathPromotesPLTspreadingDenseADP/ATPCalciumSerotoninPLTagonistRegulatesPLTactivationPromotesvasoconstrictionLysosomesProteolytic,hydrolyticenzymesDigestvesselwallmatrixanddebris1.血小板結(jié)構(gòu)⑴表面結(jié)構(gòu)⑵骨架系統(tǒng)和收縮蛋白⑶細(xì)胞器和內(nèi)容物

⑷特殊膜系統(tǒng)⒉血小板活化⒊血小板功能◆α顆?！糁旅茴w?！羧苊阁w顆粒⑷SpecialmembranesystemOpencanalicularsystem(OCS)DensetubularSystem(DTS)PLTPlasmaMembrane:OCSTubularinvaginationofmembraneTransportofsubstancesreleasedfromPLTgranulestoexteriorAdsorption/storageofhemostaticproteinsDenseTubularSystem(DTS)EndoplasmicreticulumremnantFrommegakaryocyteCalciumstorage/release1.血小板結(jié)構(gòu)⑴表面結(jié)構(gòu)⑵骨架系統(tǒng)和收縮蛋白⑶細(xì)胞器和內(nèi)容物

⑷特殊膜系統(tǒng)⒉血小板活化⒊血小板功能◆開放管道系統(tǒng)OCS◆致密管道系統(tǒng)DTS靜息血小板活化血小板2.血小板的活化2.血小板活化的表現(xiàn)

(1)形態(tài)改變

(2)特殊蛋白的表達(dá)(GPⅡb/Ⅲa，P選擇素)

(3)血漿血小板特異產(chǎn)物水平增高

(?-TG，PF4，TXA2)

◆血小板活化的分子基礎(chǔ)

1、血小板收縮(凝血酶，膠原，TXA2，PAF等)

2、血小板表面物質(zhì)的表達(dá)(PF4，GPⅡb/Ⅲa)

◆血小板代謝基礎(chǔ)

(1)能量代謝(有氧和無氧)

(2)膜磷脂的代謝

A、花生四烯酸(AA)

B、血小板活化因子(PAF)

C、血小板第3因子(PF3)花生四烯酸代謝促進(jìn)血小板聚集抑制血小板聚集1.血小板結(jié)構(gòu)⑴表面結(jié)構(gòu)⑵骨架系統(tǒng)和收縮蛋白⑶細(xì)胞器和內(nèi)容物

⑷特殊膜系統(tǒng)⒉血小板活化⒊血小板功能◆活化表現(xiàn)◆活化分子基礎(chǔ)◆活化代謝基礎(chǔ)Adhesion

GpIIb/IIIa⑴粘附功能

PlateletadhesionGpIIb/IIIaGpIIb/IIIaAggregationADPAdrenalinePlateletGpIbExposedCollagenEndotheliumvWFCOLLAGENGpIIb/IIIaGpIIb/IIIaAggregationGpIIb/IIIaGpIIb/IIIaAggregationAdhesionAdhesionADPAdrenalineTHROMBINPlateletAdhesionFollowedbyAggregationcollagenvWFsheerforces(2)聚集功能

PlateletaggregationPlateletAggregationFibrinogenTxA2FibrinogenBindingSiteADPThrombinPlateletDenseGranuleIIIaIIbADPADPIIIaIIbIIIaIIbFibrinogenEDDDGpIb/IXvWFPlateletaggregation◎GPIIb-IIIa◎Fg◎Ca2+

⑶釋放反應(yīng)SecretionDischargeofgranules’contentsMarkersofPLTactivationPF4ThromboglobulinPromote&AmplifyPLTactivitiesPrimaryhemostasisSecondaryhemostasis釋放反應(yīng)因素◎誘導(dǎo)劑◎骨架系統(tǒng)◎Ca2+GPIIb-IIIa

fibrinogenPlateletcoagulation◎PF3：PS外翻形成（參與兩個(gè)復(fù)合物形成）◎接觸產(chǎn)物生成活性（CPFA）：膠原、ADP◎膠原誘導(dǎo)的凝血活性（CICA）：膠原◎a顆粒凝血因子的釋放（FV、Fg、FXI）FibrinReinforcementofPlateletPlugBySecondary

HemostasiscollagenvWFsheerforcesBloodclotretraction總結(jié)：一期止血功能

血管壁止血功能

血小板止血功能◎收縮反應(yīng)◎粘附功能◎血小板活化◎聚集功能◎凝血系統(tǒng)激活◎釋放反應(yīng)◎抗纖溶作用◎促凝功能◎血塊收