易栓症-神内病例

易栓症Normalhemostasis（止血）VIIVIITF-VIIaXXaIIIIaFbgnFibrinsIXTFFibrinpVIIIVTFTF-VIIaIXaadhesion

粘附aggregation

聚集coagulationpathway

凝血途径Coagulationbalance

anticoagulantmechanismsprocoagulantmechanismsfibrinformation

(VIIa)Xa,IXaCa2+VIIaIIaTM+IIa

VIIa

IIa

CoagulationwaterfallPrecallicreinaXIIXIIaXIXIaIX

IXa

TF

XXaVIIIa

VaIIIIaFibrinclotXIIIa

XIIIChininogenProteinCAPCPSInhibitionIIa

VVIIaVIICallicrein

FibrinogenPlasminogenPAI-1PlasminVIIITFPIAntithrombinAPCinhibitorCa2+Ca2+Ca2+Ca2+FibrinmonomerEndothelialcellsurface

coagulationfactors

anticoagulantproteinsgain-of-functionmutations

fibrinolysisantiphospholipidAb

fibrinformationanticoagulantmechanismsprocoagulantmechanisms易栓症（Thrombophlilia）指由于抗凝蛋白、凝血因子、纤溶蛋白等的遗传性或获得性缺陷，或存在获得性危险因素，而容易发生血栓栓塞的疾病状态。不是单一的疾病。血栓栓塞类型：静脉血栓栓塞AnnualincidenceofDVT

Whites 0.8-1.2x1000 HongKongChinese 0.16x1000

Liuetal,HongKongMedJ2002

rateratio(vswhite)AfricanAmericans 1.27(1.07-1.51) Hispanic 0.60(0.54-0.67)Asians/PacificIslanders 0.26(0.22-0.30)*

Whiteetal,AnnInternMed1998*idiopathicorsecondaryVTE:amultifactorialdiseaseacquiredgeneticmixedtransientVTEriskfactors

…theoldstory.Genetic

riskfactorsinheritedthrombophilia

deficiencyofanticoagulantproteins

yearofdiscovery

antithrombin 1965

proteinC 1981

proteinS 1984ANTITHROMBIN,PROTEINC,PROTEINS:typeofdeficiencyTypeI:QuantitativedeficiencyTypeII:Qualitativedeficiency↓antigenictest↓functionaltest↓functionaltest=antigenictestPrevalenceofdeficiencies

general

unselected

population

VTEpatients antithrombin 0.02-0.2%1%

proteinC 0.1-0.5%3% proteinS ? 1-2%

RiskofVTE

associatedwithdeficiencies increase

relativerisk

antithrombin

5-50 proteinC

7-15

proteinS

6-10

Genetic

riskfactorsinheritedthrombophilia

yearofdiscovery

resistancetoactivatedproteinC

1993/94 andfactorVLeiden(G1691A)prothrombinmutation(G20210A) 1996…thenewstory.…theoldstory.Acquiredriskfactorsoftenpersistent(unremovable)olderagecancerantiphospholipidantibodiespreviousvenousthromboembolismAgeandVTE0-910-1920-2930-3940-4950-5960-6970-79>796005004003002001000Andersonetal,1991IncidenceRateper100,000FemalesMalesCancerandVTETissuefactor,constitutiveofmalignantcells,promotesangiogenesisandincreasesplasminproduction(metastases)Prothromboticcancersubstances(cancerprocoagulant,IL1β,TNF,etc.)TheriskofVTEishigherifchemotherapy(tamoxifen,thalidomide,L-asparaginase)VTEandoccultcancerMixedriskfactorsinheritedor/andacquired

yearofdiscoveryhyperhomocysteinemia 1994highfactorVIII

1995…thenewstory.…theoldstory.Transientriskfactorstemporary,

removablesurgeryandmajortraumaprolongedimmobilizationpregnancy/puerperium(6weekspostpartum)oralcontraceptives/hormonereplacementtherapyTransientriskfactorstemporary,

removable

yearofdiscoveryActivatedproteinCresistance

1993Airtravel 1999

…thenewstory.易栓症的分类遗传性易栓症获得性易栓症一、天然凝血抑制物缺乏一、易栓疾病1、遗传性抗凝血酶缺乏症1、抗磷脂抗体综合征2、遗传性蛋白C缺乏症2、肿瘤性疾病3、遗传性蛋白S缺乏症3、后天性凝血因子水平增高4、遗传性肝素辅因子-II缺乏症4、获得性抗凝蛋白缺乏二、凝血因子缺陷5、糖尿病1、遗传性抗活化的蛋白C症6、骨髓增生性疾病2、凝血酶原20210A基因突变7、肾病综合征3、异常纤维蛋白原血症8、阵发性睡眠性血红蛋白尿症4、凝血因子XII缺乏症二、易栓状态三、纤溶蛋白缺陷1、年龄增加1、异常纤溶酶原血症2、血栓形成既往史2、组织型纤溶酶原活化物（tPA）缺乏3、长时间制动3、纤溶酶原活化抑制物-1（PAI-1）增多4、创伤及围手术期四、代谢缺陷5、妊娠和产褥期1、高同型半胱氨酸血症6、口服避孕药及激素替代疗法2、高组氨酸糖蛋白增多症F：familyhistory（尤其是强家族史，即家族中有至少两例同类型血栓患者）U：unusuallocationsofthrombosis（腹腔、颅内等部位）R：recurrentepisodesofthrombosisY：year（<45y）符合上述任1条均建议筛查易栓症指标FURY易栓症初筛项目

PT、aPTT、Fib、(TT?)

抗磷脂抗体(LA、ACA)

空腹同型半胱氨酸

FVIII:C

蛋白C活性 蛋白S活性