学术讨论—中国静脉血栓栓塞症研究现状.ppt

中国中国(zhn u)(zhn u)静脉血栓栓塞症研究静脉血栓栓塞症研究现状现状赵永强赵永强北京协和医院血液科北京协和医院血液科第一页，共二十四页。静脉静脉(jngmi)(jngmi)血栓栓塞症的流行病学血栓栓塞症的流行病学(venous thromboembolism,VTE)总人群中总人群中VTE的年诊断率的年诊断率西方国家西方国家(guji)(guji)：0.52/1000。中国大陆：无大规模调查的流行病学数据。中国大陆：无大规模调查的流行病学数据。中国香港：中国香港：0.167/1000是否中国人是否中国人VTE发生率确实低于高加索人。发生率确实低于高加索人。第二页，共二十四页。malignanciesstrokeChina(Zhang,2001)2.8%(n=106)6.7%(n=120)Sweden(Nordstrom,1994)39%(n=383)UK(Johnson,1999)52%(n=258)Canada(Turpie,1992)28%(n=25)内科内科(nik)(nik)疾病中疾病中VTE的发生率的发生率第三页，共二十四页。nHip&knee replacementChina (Yang,2000)6248.4%(Li,2002)1635.4%France40013.5%USA (Davidson,1996)47470%外科外科(wik)(wik)疾病中疾病中VTE的发生率的发生率第四页，共二十四页。近近近近1010年国内杂志发表年国内杂志发表年国内杂志发表年国内杂志发表(fbio)(fbio)的有关的有关的有关的有关VTEVTE的文章数目的文章数目的文章数目的文章数目中国人中国人VTE“发生率低发生率低”需考虑的影响因素需考虑的影响因素 医师对医师对医师对医师对VTEVTE认知度？诊断认知度？诊断认知度？诊断认知度？诊断(zhndun)(zhndun)技术？技术？技术？技术？第五页，共二十四页。近近近近1010年北京协和医院新诊断年北京协和医院新诊断年北京协和医院新诊断年北京协和医院新诊断(zhndun)(zhndun)的的的的VTEVTE病例数病例数病例数病例数中国人中国人VTE“发生率低发生率低”需考虑需考虑(kol)(kol)的影响因素的影响因素 医师对医师对VTE认知度？诊断技术？认知度？诊断技术？Duplex ultrasoundDuplex ultrasoundContrast venographyContrast venographyVentilation-perfusion scanVentilation-perfusion scanCTV/HCTPACTV/HCTPA第六页，共二十四页。亚临床亚临床(ln chun)(ln chun)型型VTE比西方人多比西方人多致死性致死性VTE比西方人少比西方人少纤溶活性比西方人强？纤溶活性比西方人强？食物和其他环境因素？食物和其他环境因素？中国中国(zhn u)(zhn u)人人VTE“发生率低发生率低”的人种和饮食环境因的人种和饮食环境因素素第七页，共二十四页。VTE的遗传性危险的遗传性危险(wixin)(wixin)因素因素在高加索人群中，最常见在高加索人群中，最常见(chn jin)(chn jin)的遗传性危险因素为：的遗传性危险因素为：两种基因突变两种基因突变:因子因子V Leiden突变突变 凝血酶原凝血酶原G20210A突变突变 VTE患者中的检出率患者中的检出率50%。三种抗凝蛋白缺乏：三种抗凝蛋白缺乏：蛋白蛋白C、蛋白、蛋白S和抗凝血酶缺乏和抗凝血酶缺乏 VTE患者中的检出率患者中的检出率1015%。第八页，共二十四页。DVT患者患者(hunzh)(hunzh)中中FV Leiden突变突变*高加索人群高加索人群(rnqn)中因子中因子V Leiden突变的检出率突变的检出率37%.。APC-RAPC-RFV LeidenFV LeidenDVTDVTcontrolcontrolDVTDVTcontrolcontrolChinese Han nationalityChinese Han nationality Mainland Mainland (Chu,1996)(Chu,1996)5/315/31(16%)(16%)5/1065/106(4.7%)(4.7%)0/310/310/1410/141 (Bai,2000)(Bai,2000)4/874/87(4.6%)(4.6%)0/600/600/870/870/600/60 Taiwan Taiwan (Shen,1997)(Shen,1997)0/850/850/850/85Chinese Kazak nationalityChinese Kazak nationality (Xing,2001)(Xing,2001)3/853/85(3.5%)(3.5%)JapanJapan (Zama,1996)(Zama,1996)3/333/33(9%)(9%)0/630/630/290/290/530/53Europe Europe (Koster,1993)(Koster,1993)1 1 (den Heijer,1996)(den Heijer,1996)2 264/30164/301(21%)(21%)1 114/30114/301(5%)(5%)1 147/26947/269(17.5)(17.5)2 27/2697/269(2.6%)(2.6%)2*2*第九页，共二十四页。DVT患者患者(hunzh)(hunzh)中凝血酶原基因中凝血酶原基因G20210A突变突变*高加索人群高加索人群(rnqn)中凝血酶原中凝血酶原G20210A突变约占突变约占 2%。Prothrombin gene Prothrombin gene G20210A mutationG20210A mutationDVTDVTcontrolcontrolChinaChina (Bai,2000)(Bai,2000)0/980/980/1000/100 (He,2002)(He,2002)0/1030/1030/1060/106UKUK (Cumming,1997)(Cumming,1997)12/219 12/219(5.5%)(5.5%)2/1642/164 (1.2%)(1.2%)HollandHolland(Poort,1996)(Poort,1996)18%18%1%1%*第十页，共二十四页。DVT患者患者(hunzh)(hunzh)中抗凝蛋白缺乏中抗凝蛋白缺乏n nDeficient proteinsDeficient proteinsATATPCPCPSPSTotalTotalChinaChina Mainland Mainland (Bai,2000)(Bai,2000)87875 5(5.7%)(5.7%)8 8(9.2%)(9.2%)1313(14.9%)(14.9%)2626(29.9%)(29.9%)Taiwan Taiwan (Shen,1997)(Shen,1997)85853 3(3.5%)(3.5%)1616(18.8%)(18.8%)2828(32.9%)(32.9%)4747(55.3%)(55.3%)Hong kong Hong kong (Liu,1994)(Liu,1994)52525 5(9.6%)(9.6%)9 9(17.3%)(17.3%)1010(19.2%)(19.2%)2424(46.1%)(46.1%)JapanJapan (Suehisa,2001 (Suehisa,20011131132 2(1.8%)(1.8%)9 9(8.0%)(8.0%)2020(17.7%)(17.7%)3131(27.4%)(27.4%)EuropeEurope (den Heijer,1996)(den Heijer,1996)2692691010(3.7%)(3.7%)1515(5.6%)(5.6%)7 7(2.6%)(2.6%)3232(11.9%)(11.9%)第十一页，共二十四页。DVT患者患者(hunzh)(hunzh)中高同型半胱氨酸血症中高同型半胱氨酸血症Plasma homocysteinePlasma homocysteine(mol/L)(mol/L)P PDVTDVTControlControlChinaChina(Qiu,2003)(Qiu,2003)13.08.713.08.7(n=69)(n=69)10.14.310.14.3(n=111)(n=111)0.050.05 (Gao,2003)(Gao,2003)14.511.014.511.0(n=33)(n=33)10.74.610.74.6(n=33)(n=33)0.010.050.05HollandHolland(den Heijer,(den Heijer,1996)1996)12.9(4.8-60.2)12.9(4.8-60.2)(n=269)(n=269)12.3(6.4-37.5)12.3(6.4-37.5)(n=269)(n=269)第十二页，共二十四页。高同型半胱氨酸血症定义高同型半胱氨酸血症定义(dngy)为高于对照组为高于对照组90*或或 95#百分位水平。百分位水平。DVT患者患者(hunzh)(hunzh)中高同型半胱氨酸血症中高同型半胱氨酸血症hyperhomocysteinemiahyperhomocysteinemiaOddsOddsRatioRatioDVTDVTControlControlChina China (Qiu,2003)(Qiu,2003)*15/69 15/69 (21.7%)(21.7%)11/111 11/111(9.9%)(9.9%)2.52.5 (Gao,2003)(Gao,2003)*21/33 21/33 (63.6%)(63.6%)4/33 4/33 (12.1%)(12.1%)9.59.5HollandHolland(den Heijer,(den Heijer,1996)1996)#28/269 28/269(10.4%)(10.4%)13/269 13/269(4.8%)(4.8%)2.52.5第十三页，共二十四页。VTE遗传性危险因素遗传性危险因素(yn s)(yn s)小结小结抗凝蛋白抗凝蛋白抗凝蛋白抗凝蛋白缺乏缺乏缺乏缺乏(quf)(quf)其他其他其他其他(qt)(qt)/未明未明未明未明APC-RAPC-R(Genetic defect?)(Genetic defect?)APC-RAPC-R(FV Leiden)(FV Leiden)中国汉族人群中国汉族人群中国汉族人群中国汉族人群高加索人群高加索人群高加索人群高加索人群其他其他其他其他/未明未明未明未明抗凝蛋白抗凝蛋白抗凝蛋白抗凝蛋白缺乏缺乏缺乏缺乏第十四页，共二十四页。WuWu19941994DVTDVTYangYang19961996DVTDVTXuXu20002000DVTDVTPanPan19991999PTEPTEAoAo20032003PTEPTEGuoGuo20032003PTEPTEWangWang20042004VTEVTETotal Total(%)(%)n n23123117617610310362621491491061062182181045*1045*phlebitis/Varicosisphlebitis/Varicosis4444151513132 2555560601111200 200 (19.1%)(19.1%)surgerysurgery2626454524241111111118184646181 181 (17.3%)(17.3%)Trama/fractureTrama/fracture2121323220201010252523234141172 172 (16.5%)(16.5%)Prolonged bed rest Prolonged bed rest/Immobilazation/Immobilazation353531311 135354 4 106 106(10.1%)(10.1%)malignanciesmalignancies7 75 514141111101010102323 80 80 (7.7%)(7.7%)Hypertension/Hypertension/AtherosclerosisAtherosclerosis232320201 11414 58 58 (6.2%)(6.2%)Chronic heart Chronic heart diseasesdiseases13134 418181111 46 46 (4.9%)(4.9%)Pregnancy/deliveryPregnancy/delivery13138 81 12 21 1 25 25 (2.4%)(2.4%)CTDCTD8 81 12 24 4 14 14 (1.5%)(1.5%)NSNS1 16 66 61 1 8 8 (0.9%)(0.9%)othersothers57572929444410106 66 64 4156 156 (14.9%)(14.9%)unknownunknown2828181812127 7212128286262176 176 (16.8%)(16.8%)*One patient may have more than one factors.*One patient may have more than one factors.VTE获得性危险因素获得性危险因素(yn s)(yn s)分析分析第十五页，共二十四页。WuWu19941994DVTDVTYangYang19961996DVTDVTXuXu20002000DVTDVTPanPan19991999PTEPTEAoAo20032003PTEPTEGuoGuo20032003PTEPTEWangWang20042004VTEVTETotal Total(%)(%)n n23123117617610310362621491491061062182181045*1045*phlebitis/Varicosisphlebitis/Varicosis4444151513132 2555560601111200 200 (19.1%)(19.1%)surgerysurgery2626454524241111111118184646181 181 (17.3%)(17.3%)Trama/fractureTrama/fracture2121323220201010252523234141172 172 (16.5%)(16.5%)Prolonged bed rest Prolonged bed rest/Immobilazation/Immobilazation353531311 135354 4 106 106(10.1%)(10.1%)malignanciesmalignancies7 75 514141111101010102323 80 80 (7.7%)(7.7%)Hypertension/Hypertension/AtherosclerosisAtherosclerosis232320201 11414 58 58 (6.2%)(6.2%)Chronic heart Chronic heart diseasesdiseases13134 418181111 46 46 (4.9%)(4.9%)Pregnancy/deliveryPregnancy/delivery13138 81 12 21 1 25 25 (2.4%)(2.4%)CTDCTD8 81 12 24 4 14 14 (1.5%)(1.5%)NSNS1 16 66 61 1 8 8 (0.9%)(0.9%)othersothers57572929444410106 66 64 4156 156 (14.9%)(14.9%)unknownunknown2828181812127 7212128286262176 176 (16.8%)(16.8%)*One patient may have more than one factors.*One patient may have more than one factors.VTE获得性危险获得性危险(wixin)(wixin)因素分析因素分析根据两项全国范围的调查，外周血根据两项全国范围的调查，外周血管病患者中有静脉炎或静脉曲张者管病患者中有静脉炎或静脉曲张者占占1219.6%1219.6%，明显高于西方国家，明显高于西方国家，明显高于西方国家，明显高于西方国家，原因原因原因原因(yunyn)(yunyn)不明。不明。不明。不明。第十六页，共二十四页。WuWu19941994DVTDVTYangYang19961996DVTDVTXuXu20002000DVTDVTPanPan19991999PTEPTEAoAo20032003PTEPTEGuoGuo20032003PTEPTEWangWang20042004VTEVTETotal Total(%)(%)n n23123117617610310362621491491061062182181045*1045*phlebitis/Varicosisphlebitis/Varicosis4444151513132 2555560601111200 200 (19.1%)(19.1%)surgerysurgery2626454524241111111118184646181 181 (17.3%)(17.3%)Trama/fractureTrama/fracture2121323220201010252523234141172 172 (16.5%)(16.5%)Prolonged bed rest Prolonged bed rest/Immobilazation/Immobilazation353531311 135354 4 106 106(10.1%)(10.1%)malignanciesmalignancies7 75 514141111101010102323 80 80 (7.7%)(7.7%)Hypertension/Hypertension/AtherosclerosisAtherosclerosis232320201 11414 58 58 (6.2%)(6.2%)Chronic heart Chronic heart diseasesdiseases13134 418181111 46 46 (4.9%)(4.9%)Pregnancy/deliveryPregnancy/delivery13138 81 12 21 1 25 25 (2.4%)(2.4%)CTDCTD8 81 12 24 4 14 14 (1.5%)(1.5%)NSNS1 16 66 61 1 8 8 (0.9%)(0.9%)othersothers57572929444410106 66 64 4156 156 (14.9%)(14.9%)unknownunknown2828181812127 7212128286262176 176 (16.8%)(16.8%)*One patient may have more than one factors.*One patient may have more than one factors.2 risk factors:58%2 risk factors:58%3 risk factors:31%3 risk factors:31%4 risk factors:14%4 risk factors:14%VTE获得性危险因素获得性危险因素(yn s)(yn s)分析分析第十七页，共二十四页。VTE患者患者(hunzh)(hunzh)的性别分布的性别分布汇总几项大宗汇总几项大宗(dzng)(dzng)国内研究，国内研究，1741名名VTE患者患者的性别分布为：的性别分布为：男男:女女=1091:650(1.68:1)国外同类研究：高加索人群和其他亚洲人群中国外同类研究：高加索人群和其他亚洲人群中无明显性别差异。无明显性别差异。第十八页，共二十四页。VTE患者的年龄分布患者的年龄分布(fnb)(fnb)汇总几项大宗国内研究，汇总几项大宗国内研究，汇总几项大宗国内研究，汇总几项大宗国内研究，17411741名名名名VTEVTE患者的性别分布为：患者的性别分布为：患者的性别分布为：患者的性别分布为：13901390（中位年龄（中位年龄（中位年龄（中位年龄 49.7)49.7)N=576 Data from:Xu,2000 Data from:Xu,2000 Ao,2003 Ao,2003 Guo,2003 Guo,2003 Wang,2004 Wang,2004The first episodes of VTE were most common at age The first episodes of VTE were most common at age 4060,that was about 10 years younger than that of 4060,that was about 10 years younger than that of Caucasians.Caucasians.第十九页，共二十四页。90%of DVT 90%of DVT involved lower involved lower limbes limbes Frequencies of PTE in Frequencies of PTE in the patients presented the patients presented with DVT:11.144.7%with DVT:11.144.7%Frequencies of DVT Frequencies of DVT in the patients in the patients presented with PTE:presented with PTE:4266%4266%汇总汇总汇总汇总(huzng)(huzng)几项大宗几项大宗几项大宗几项大宗国内研究，计国内研究，计国内研究，计国内研究，计17411741名名名名VTEVTE患者患者患者患者第二十页，共二十四页。2001 Guideline on diagnosis and treatment of PTE2001 Guideline on diagnosis and treatment of PTE The Society of Respiratory diseasesThe Society of Respiratory diseasesChinese Medical AssociationChinese Medical AssociationClinical suspicion of PTEClinical suspicion of PTEVentilation and perfusion scanVentilation and perfusion scanCompression ultrasound venographyCompression ultrasound venographyD-Dimer D-Dimer Confirmation of PTEConfirmation of PTEHCTPA or Contrast PA if HCTPA or Contrast PA if necessarynecessaryAnticoagulant Anticoagulant therapytherapyFibrinolytic therapy if Fibrinolytic therapy if indicatedindicated(+)(+)(-)(-)Exclusion of PTEExclusion of PTEFellowup if necessaryFellowup if necessary(-)(-)(+)(+)Risk factor screenRisk factor screenHCTPA:helical CT pulmonary angiography第二十一页，共二十四页。总的印象总的印象(ynxing)(ynxing)汉族人与高加索人相比：汉族人与高加索人相比：VTE的发生率可能较低，但这需经进一步大的发生率可能较低，但这需经进一步大规模流行病学规模流行病学(li xn bn xu)(li xn bn xu)研究的证实。研究的证实。抗凝蛋白缺乏，尤其是蛋白抗凝蛋白缺乏，尤其是蛋白S的缺乏，是最的缺乏，是最常见的遗传性缺陷。常见的遗传性缺陷。发病年龄较轻，需进一步证实。即使确如此，发病年龄较轻，需进一步证实。即使确如此，原因尚难解释。原因尚难解释。第二十二页，共二十四页。AcknowledgmentPeking Union Medical College Bai Chun-mei,et al.Natl Med J china,1999,79:900 Bai Chun-mei,et al.Chin J Intern Med,2000,39:746 Zhang Xiao-fei,et al.Chin J Contr Chron Non-commun Dis,2001,9:206 He Jian-guo,et al.Natl Med J china,2001,81:1490 He Jian-guo,et al.Natl Med J china,2002,82:1730 Qiu Ling,et al.Acta Acad Med Sin,2003,25:706 Gao Ying,et al.J Cardiovasc Pulmon Dis,22:222 Pan Jia-qi,et al.Natl Med J china,1999,79:354 Xu Ling,et al.Chin J Intern Med,2000,39:513Beijing Medical University Yang Gang,et al.Chin J Surg,2000,38:25 Guo Danjie,et al.Chin J Cardiol,2003,31:49 Shanghai Second Medical University Chu Hai-yan,et al.Chin J Hematol,1996,17:462 Yang Jing-wen,et al.Shanghai Med J,19:90Second Military Medical University Wang Mei-tang,et al.Acad J Sec Mil Med Univ,2004,24:740Chinese Medical University Ao Ran,et al.J Chin Med Univ,2003,32:562Capital Medical University Wang Chen,et al.Chin J Tuberc Respir Dis,2001,24:259第二十三页，共二十四页。内容(nirng)总结中国静脉血栓栓塞症研究现状。静脉血栓栓塞症的流行病学(li xn bn xu)(venous thromboembolism,VTE)。西方国家：0.52/1000。中国香港：0.167/1000。是否中国人VTE发生率确实低于高加索人。(den Heijer,1996)2。Japan(Fujimura,2000)。高同型半胱氨酸血症定义为高于对照组90*或 95#百分位水平。176 (16.8%)。谢谢第二十四页，共二十四页。