易栓癥-神內(nèi)病例

易栓癥Normalhemostasis（止血）VIIVIITF-VIIaXXaIIIIaFbgnFibrinsIXTFFibrinpVIIIVTFTF-VIIaIXaadhesion

粘附aggregation

聚集coagulationpathway

凝血途徑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易栓癥（Thrombophlilia）指由于抗凝蛋白、凝血因子、纖溶蛋白等的遺傳性或獲得性缺陷，或存在獲得性危險(xiǎn)因素，而容易發(fā)生血栓栓塞的疾病狀態(tài)。不是單一的疾病。血栓栓塞類型：靜脈血栓栓塞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.易栓癥的分類遺傳性易栓癥獲得性易栓癥一、天然凝血抑制物缺乏一、易栓疾病1、遺傳性抗凝血酶缺乏癥1、抗磷脂抗體綜合征2、遺傳性蛋白C缺乏癥2、腫瘤性疾病3、遺傳性蛋白S缺乏癥3、后天性凝血因子水平增高4、遺傳性肝素輔因子-II缺乏癥4、獲得性抗凝蛋白缺乏二、凝血因子缺陷5、糖尿病1、遺傳性抗活化的蛋白C癥6、骨髓增生性疾病2、凝血酶原20210A基因突變7、腎病綜合征3、異常纖維蛋白原血癥8、陣發(fā)性睡眠性血紅蛋白尿癥4、凝血因子XII缺乏癥二、易栓狀態(tài)三、纖溶蛋白缺陷1、年齡增加1、異常纖溶酶原血癥2、血栓形成既往史2、組織型纖溶酶原活化物（tPA）缺乏3、長時間制動3、纖溶酶原活化抑制物-1（PAI-1）增多4、創(chuàng)傷及圍手術(shù)期四、代謝缺陷5、妊娠和產(chǎn)褥期1、高同型半胱氨酸血癥6、口服避孕藥及激素替代療法2、高組氨酸糖蛋白增多癥F：familyhistory（尤其是強(qiáng)家族史，即家族中有至少兩例同類型血栓患者）U：unusuallocationsofthrombosis（腹腔、顱內(nèi)等部位）R：recurrentepisodesofthrombosisY：year（<45y）符合上述任1條均建議篩查易栓癥指標(biāo)FURY易栓癥初篩項(xiàng)目

PT、aPTT、Fib、(TT?)

抗磷脂抗體(LA、ACA)

空腹同型半胱氨酸

FVIII:C

蛋白C活性 蛋白S活性