內(nèi)科病人靜脈血栓栓塞性疾病李小鷹

內(nèi)科病人靜脈血栓栓塞性疾病李小鷹全面認識VTE全球VTE的發(fā)生率居高不下VTE是患者死亡的主要因素VTE帶來沉重的負荷多數(shù)VTE的發(fā)生與入院時存在的基礎(chǔ)疾病和手術(shù)情況相關(guān)院內(nèi)或院外適宜的靜脈血栓預(yù)防可降低VTE所帶來的危害。VTE是可預(yù)防的嚴峻的公共衛(wèi)生保健問題1CohenAT.Presentedatthe5thAnnualCongressoftheEuropeanFederationofInternalMedicine;2005.2Eurostatstatisticsonhealthandsafety2001.Availablefrom:.VTE所致死亡觸目驚心VTE所導(dǎo)致的死亡例數(shù):543,4541

（2005第5歐盟內(nèi)科年會）VTE所致死亡超過了以下原因所致死亡的總數(shù):AIDS

5,8602乳腺癌 86,8312前列腺癌 63,6362交通事故 53,59922006年中國住院患者PTE死亡率達9.74%內(nèi)科患者VTE：一個被低估的全球疾病負擔(dān)住院人群統(tǒng)計，死亡者中10%死于PTE1PTE死亡者中，75%合并有內(nèi)科疾病2住院期間17%的重癥患者發(fā)生癥狀性DVT375%的內(nèi)科重癥患者存在2個以上VTE的危險因素41.SandlerDAetal.JRSocMed1989;82:203-5.2.BaglinTPetal.JClinPathol1997;50:609–10.3.MismettiPetal.ThrombHaemost2000;83:14–9.4.AndersonFAetal.JVascSurg1992;19:557-8內(nèi)科住院患者VTE患病率未經(jīng)治療時DVT的危險性

0%

12%22%28～33% 30～50%內(nèi)科腦卒中偏癱

ICUAMI1.LeizoroviczandMismetti.Circulation2004;110(SupplIV):13–9.

2.FraisseF,etal.AmJRespirCritCareMed.,2000.161:1109-1114.

3.SpyropoulosAC,etal.Chest2005.128:958-969.4.CohenAT,etal.ThrombHaemost2005.94:750-759.內(nèi)科住院患者VTE患病率國外前瞻性研究1.SamamaMMetal.NEnglJMed1999;341:79–3800.

2.LeizoroviczAetal.Circulation2004;110:874–79.3.CohenATetal.BMJ2005;inpress.致死性PEDVT所有致死性PE病例在死亡前得到診斷的不足一半

1約80%DVT病例無臨床表現(xiàn)2,3VTE經(jīng)常得不到及時診斷1.GoldhaberSZ,etal.AmericanJournalofMedicine1982;73:822-826.2.LethenH,etal.AmericanJournalofCardiology1997;80:1066-1069.3.SandlerDA,etal.J.RoyalSoc.Med.1989;82:203-205.住院接受內(nèi)科治療的患者屬于VTE高危人群靜脈血流緩慢血管內(nèi)皮受損極高危中/高危低/中危高凝狀態(tài)中國PTE發(fā)病并不少見全國PTE-DVT形成防治協(xié)作組報道的PTE病例數(shù)（年）

老年內(nèi)科住院患者VTE事件發(fā)生率調(diào)查VTEinClinicalMedicalElderlyPatients

(VTE-CMEP)VTE-CMEP研究VTE-CMEP

研究方案0天14-21天90天入選老年內(nèi)科急癥住院患者607例首次隨訪CUS二次隨訪VTE事件，CUS三次隨訪電話VTE事件VTE-CMEP

主要終點事件主要終點事件90天內(nèi)客觀檢查證實的DVT；90天內(nèi)客觀檢查證實的致死性或非致死性PE；客觀檢查證實的無癥狀的DVT。次要終點事件90天內(nèi)全因死亡。

入選患者基礎(chǔ)疾病情況%心力衰竭60.6%代謝性疾病42.0%內(nèi)臟炎癥29.9%慢性腎功能不全26.5%急性冠脈綜合癥24.5%急性腦梗塞10.5%呼吸衰竭10.0%惡性腫瘤5.9%VTE病史3.8%VTE-CMEP

主要終點事件主要終點患病率（％）9.7%01.534.567.59VTE事件7.3%2.1%DVTPEDVT+PE0.5%內(nèi)科急癥不同患者VTE的發(fā)生率COPD伴急性呼吸衰竭18.8%呼吸衰竭16.4%急性腦梗塞15.6%急性感染性疾病14.3%急性冠脈綜合癥8.7%心力衰竭7.6%急性心肌梗死4.2%不同基礎(chǔ)疾病VTE發(fā)生率VTE史34.8%靜脈曲張20.5%慢性內(nèi)臟炎癥疾病14.3%惡性腫瘤11.1%肥胖10.7%慢性腎功能不全8.7%代謝疾病8.2%不同治療措施患者VTE發(fā)生率

呼吸衰竭伴機械通氣23.5%中心靜脈導(dǎo)管18.9%永久性起搏器17.6%VTE–CMEP與其他研究結(jié)果比較0246810121416MEDENOXPREVENTCMEPVTE發(fā)病率（％）4.96%14.9%9.7%ARTEMIS10.5%內(nèi)科高危患者接受VTE預(yù)防不足IMPROVE研究：1500例內(nèi)科高?；颊?9％ENDORSE研究：

37356例內(nèi)科高?；颊?0％國內(nèi)（CMEP與RAMP）研究

1854例內(nèi)科高?；颊?0％VTE-CMEP研究預(yù)防VTE治療情況

項目首次隨訪二次隨訪末次隨訪抗凝藥物普通肝素13.0%6.0%0.9%低分子肝素7.1%3.0%0華法令5.4%6.8%4.0%機械性預(yù)防彈力襪00.3%0.2%下肢循環(huán)驅(qū)動器000肢體按摩04.0%1.4%VTE-RAMP研究

ICU/CCU內(nèi)科急癥住院患者VTE風(fēng)險評估和預(yù)防治療現(xiàn)況調(diào)查（VTE—RiskAssessmentandProphylaxisTreatmentamongAcute

MedicalPatientsinICU/CCUinChina–Across-sectionalSurvey）

ICUvsCCU

符合標準病人入組情況(

N

=

1247

)CCU(N=704)ICU(N=543)內(nèi)科重癥患者VTE危險因素比例

評估的患者中，有99.0%的患者采用血栓預(yù)防治療后受益的證據(jù)，其中57.8%患者有多重危險因素危險因素個數(shù)接受ACCP指南推薦的預(yù)防措施的比例**ACCP指南推薦的內(nèi)科重癥患者的預(yù)防方法包括：無藥物預(yù)防禁忌患者使用普通肝素或低分子肝素;有藥物預(yù)防禁忌患者使用機械預(yù)防方法（彈力襪或充氣加壓裝置）ENDORSE研究-----急癥住院VTE危險患者流行病學(xué)國際評估研究ENDORSE-Epidemiologic

InterNationalDay

forthe

EvaluatiOnofPatientsat

RiskofVenousThrombosisintheAcuteHospitalCare

Setting外科及內(nèi)科患者所占比例(

N

=

68,183

)外科患者(N=30,827)內(nèi)科患者(N=37,356)主要研究目的42

%

存在VTE危險內(nèi)科患者(

n

=

37,356

)次要研究目的40

%

接受了

ACCP

治療推薦64

%

存在VTE危險59

%

接受了ACCP

推薦治療外科患者(n

=30,827

)內(nèi)科VTE高危并接受推薦預(yù)防治療的患者52

%

存在VTE危險50

%

接受了ACCP

推薦治療總計(

N=68,183

)內(nèi)外科VTE高危患者接受推薦預(yù)防治療情況

外科患者內(nèi)科患者8882665947髖/膝關(guān)節(jié)置換髖部骨折胃部疾病結(jié)腸疾病泌尿系統(tǒng)疾病45414025急性呼吸系統(tǒng)疾病急性心衰肺部感染缺血性卒中0255075100%0255075100%內(nèi)科住院患者VTE機械性預(yù)防

機械性預(yù)防措施分級加壓彈力襪（GCS）間歇充氣加壓泵（IPC）足底靜脈泵（VFP）缺血性腦卒中患者應(yīng)用10d后經(jīng)超聲診斷的DVT發(fā)生率GCS+IPC預(yù)防組為4.7%單用GCS預(yù)防組為15.9%

LacutK,etal.Neurology,2005.65:865-869

內(nèi)科VTE藥物預(yù)防療效

低劑量普通肝素（LDUH）低分子肝素（LMWH）

MEDENOXPREVENT

PRINCEPRINCE-II磺達肝癸鈉

ARTEMIS使用肝素進行血栓預(yù)防治療可顯著獲益012345相對危險性肝素較好肝素較差Belch1981Dahan1986Ibara-Perez1988Bergmann1996Gardlund1996Fraisse1998總PEMismettiP,etal.ThrombHaemost2000;83:14-19.RR=0.48[0.34-0.68],P<0.001方差分析：P=NS低分子肝素杰出的療效進一步被證實幾項較大的研究結(jié)果顯示，低分子肝素預(yù)防內(nèi)科住院患者VTE顯著優(yōu)于安慰劑研究病例數(shù)藥物治療VTE發(fā)病率OR95%CINNTP

MEDENOX1102依諾肝素20mg,qd,14天

40mg,qd,14天5.5％0.370.22-0.639例<0.001安慰劑14天14.9％

PREVENT3681達肝素5000IU,qd,14天2.6％0.550.38-0.8045例=0.002安慰劑14天5.0％

ARTEMIS

849Fondparinux2.5mg,qd,14天1.5％0.530.31-0.92=0.085安慰劑3.4％NNT:每挽救1例VTE所需要治療的病人數(shù)0481216所有靜脈栓塞事件所有近端的深靜脈血栓事件安慰劑(n=288)依諾肝素40mg(n=291)P=0.037P=0.0002NS患者(%)DVT,深靜脈血栓;PE,肺栓塞NS,無顯著意義;VTE,靜脈血栓栓塞;RRR,相對風(fēng)險降低RRR63%依諾肝素4000AXaIU使近端DVT風(fēng)險降低65％，

此益處在3個月隨訪時仍然存在RRR65%14天治療期間的靜脈血栓栓塞性事件：Medenox研究：患者隨機分組，分別接受依諾肝素20毫克或依諾肝素40毫克治療，或者給予安慰劑，接受依諾肝素20mg治療的患者與接受安慰劑治療的患者相比，其預(yù)后沒有顯示顯著差異。Samamaetal.Acomparisonofenoxaparinwithplaceboforthepreventionofvenousthromboembolisminacutelyillmedicalpatients.ProphylaxisinMedicalPatientswithEnoxaparinStudyGroup.NEnglJMed1999;341:793-800

MEDENOX研究

PREVENT研究結(jié)果

21天時，達肝素（法安明）顯著降低主要終點發(fā)生率達

45％

主要終點：DVT/PE/猝死法安明5000IU組安慰劑組主要終點發(fā)病率（％）2.77%4.96%01234545％P=0.0015LeizoroviczA,etal.Circulation2004;110:874-879.內(nèi)科治療病人預(yù)防靜脈血栓形成依諾肝素是唯一一種LMWH已經(jīng)在國內(nèi)外注冊用于預(yù)防內(nèi)科治療患者的靜脈血栓形成MEDENOXn=11021PRINCEn=4512PRINCEIIn=20630246810121416VTE;第1-14天(%)P<0.001024681012VTE(%)024681012141618VTE(%)0510152025303540VTE(%)P=0.015等效性檢驗AP=0.014等效性檢驗AP=0.044依諾肝素40mg(4000IU抗Xa)qd依諾肝素20mg(2000IU抗Xa)qd安慰劑qd肝素鈣5000IUs.c.tidVTE,venousthromboemboliceventsLMWH,low-molecular-weightheparin1.SamamaMM,etal.NEnglJMed1999;341:793-800.2.Kleberetal.ThrombHaemost1999;(suppl)1552.3.Kleberetal.UnpublishedDataA.等效性檢驗：兩種治療等效，等效的定義是兩組的最大差異為4%低分子肝素與普通肝素療效比較普通肝素更好低分子肝素更好DVTPE死亡大出血P=NSP=NSP=NSP=0.049012相對危險性MismettiP,etal.ThrombHaemost2000;83:14-19.內(nèi)科住院患者靜脈血栓栓塞癥預(yù)防中國專家建議寫作組

中華醫(yī)學(xué)會老年醫(yī)學(xué)分會

中華醫(yī)學(xué)會呼吸病學(xué)分會

中華老年醫(yī)學(xué)雜志編輯委員會

中華結(jié)核和呼吸雜志編輯委員會

——中華老年醫(yī)學(xué)雜志中華呼吸結(jié)核雜志2009年第一期內(nèi)科住院患者靜脈血栓栓塞癥預(yù)防中國專家建議中國專家建議預(yù)防性治療的指征與方法一、需要進行VTE預(yù)防性治療的內(nèi)科患者二、VTE預(yù)防性治療的方法（一）機械性預(yù)防措施（二）藥物預(yù)防性治療三、一些特殊臨床情況下的VTE預(yù)防性治療１、急性心肌梗死２、急性腦卒中３、重癥監(jiān)護病房（ICU）患者４、惡性腫瘤５、腎功能不全四、幾點說明需要進行VTE預(yù)防性治療的內(nèi)科患者Foracutelyillmedicalpatientsadmittedtohospitalwithcongestiveheartfailure

orsevererespiratorydisease

or

whoareconfinedtobedandhaveoneormoreadditionalriskfactorsactivecancer,previousVTE,sepsis,acuteneurologicdisease,orinflammatoryboweldisease

——ACCP8thEditionguidelines需要進行VTE預(yù)防性治療的內(nèi)科患者

國內(nèi)專家建議

40歲以上因急性內(nèi)科疾病住院患者，和臥床≥3d，同時合并下列病癥或危險因素之一呼吸衰竭、COPD急性加重、急性腦梗死、心力衰竭（NYHAⅢ或Ⅳ級）、急性感染性疾?。ㄖ匕Y感染或感染中毒癥）、急性冠狀動脈綜合征、VTE病史、惡性腫瘤、炎性腸病、慢性腎臟疾病、下肢靜脈曲張、肥胖（體重指數(shù)＞30kg／m２）及高齡（年齡≥75歲）。VTE預(yù)防性治療的方法機械性預(yù)防措施適應(yīng)證無機械預(yù)防性治療禁忌證的VTE高?；颊?，建議與藥物預(yù)防聯(lián)合應(yīng)用對抗凝藥物治療有禁忌證的VTE高危患者出血性腦卒中或缺血性腦卒中，抗凝治療弊大于利的患者患肢無法或不宜應(yīng)用機械性預(yù)防措施者可在對側(cè)實施預(yù)防VTE預(yù)防性治療的方法機械性預(yù)防措施禁忌證嚴重下肢動脈硬化性缺血充血性心力衰竭肺水腫下肢DVT（GCS除外）血栓性靜脈炎下肢局部嚴重病變（皮炎、壞疽、近期手術(shù)及嚴重畸形）VTE預(yù)防性治療的方法藥物預(yù)防性治療單獨應(yīng)用阿司匹林無助于預(yù)防VTELDUH方法：5000U，SC，1次／12h，6-14d禁忌證:出血性疾病凝血功能障礙外傷與術(shù)后滲血先兆流產(chǎn)惡性高血壓細菌性心內(nèi)膜炎對肝素過敏者VTE預(yù)防性治療的方法LDUH應(yīng)用中需要特別重視的幾個問題密切觀察出血并發(fā)癥和嚴重出血危險發(fā)生出血，立即停用肝素，可靜脈注射硫酸魚精蛋白（1mg／100U肝素）對高危人群監(jiān)測APTT以調(diào)整劑量年齡≥75歲腎功能不全進展期腫瘤監(jiān)測血小板計數(shù)，警惕HITVTE預(yù)防性治療的方法LMWH使用方法依諾肝素40mg，1次／d達肝素5000U，1次／d療程：6-14d禁忌證對LMWH過敏其余禁忌證同普通肝素磺達肝癸鈉2.5mg，1次／d，建議治療6～14d住院患者血栓預(yù)防治療流程患者是否屬于高危人群是患者是否無法接受藥物性血栓預(yù)防開始血栓預(yù)防治療：法安明5000IU/依諾肝素4000IU1/d或普通肝素5000IU1/12h血栓預(yù)防治療一般需要維持6-14天，同時應(yīng)考慮其他臨床因素或住院時間的長短以確定血栓預(yù)防的療程隨著病情的變化，對可能導(dǎo)致靜脈血栓栓塞性疾病的危險因素進行重新評估考慮非藥物血栓預(yù)防方法如彈力襪，間歇式氣壓治療儀，足底泵否否是一些特殊臨床情況下VTE預(yù)防性治療急性心肌梗死（AMI）無需常規(guī)用藥預(yù)防VTE經(jīng)評估VTE高危的AMI患者如無禁忌證，可延長LMWH治療時間至２周延長治療期間改為預(yù)防劑量可聯(lián)合使用機械性預(yù)防措施一些特殊臨床情況下VTE預(yù)防性治療急性腦卒中缺血性腦卒中無禁忌證，給予LDUH或LMWH用藥前必須仔細權(quán)衡血栓和出血的風(fēng)險建議聯(lián)合機械性預(yù)防措施預(yù)防VTE出血性腦卒中如無禁忌證，應(yīng)使用機械性預(yù)防措施預(yù)防VTE一些特殊臨床情況下VTE預(yù)防性治療ICU患者無禁忌證，使用LDUH或LMWH進行預(yù)防，并建議聯(lián)合應(yīng)用機械方法預(yù)防VTE；有高出血風(fēng)險的患者，先采取GCS和（或）IPC預(yù)防血栓直至出血風(fēng)險降低，然后用藥物代替機械方法預(yù)防血栓，或藥物與機械方法聯(lián)合應(yīng)用；對藥物和機械預(yù)防措施均有禁忌證的患者，應(yīng)加強臨床監(jiān)護和床旁超聲檢查，以盡早發(fā)現(xiàn)和治療VTE一些特殊臨床情況下VTE預(yù)防性治療惡性腫瘤因內(nèi)科急癥住院的VTE高危惡性腫瘤患者，建議常規(guī)給予血栓預(yù)防性治療行化療或糖皮質(zhì)激素治療的惡性腫瘤患者，不建議常規(guī)使用血栓預(yù)防性治療進展期乳腺癌接受化療者，可考慮應(yīng)用低劑量華法林預(yù)防性治療置有中心靜脈導(dǎo)管的惡性腫瘤患者，不推薦常規(guī)使用藥物預(yù)防血栓形成一些特殊臨床情況下VTE預(yù)防性治療腎功能不全對嚴重腎功能不全的患者，建議選擇LDUH作為預(yù)防性抗凝治療的藥物肌酐清除率＜30ml／min的患者，如選擇LMWH，建議減量使用應(yīng)用LMWH時，如有條件，建議每1～2天監(jiān)測凝血因子Xa水平，據(jù)此調(diào)整劑附一：肝素誘導(dǎo)的血小板減少癥(略)附二：內(nèi)科患者靜脈血栓栓塞癥治療原則(略)謝謝！5354PrevalenceandPreventionofVenousThromboembolisminMedicalPatientsLiXiaoYing,MDChinesePLAGeneralHospital

BEIJING,CHINA55ClinicalReviewofVenousThromboembolismTheincidenceofvenous

thromboembolism(VTE)isincreasingVTEisresponsibleforalargenumberofhospitaldeathsVTEisaheavyburdenglobally

ThemajorityofVTEisassociatedwithunderlyingdisordersandsurgicalconditionsAppropriatethromboprophylaxishasbeenshowntobeeffectiveandsafeformostVTEpatientsAbigchallengeforpublichealthandhealthcare1

CohenAT.Presentedatthe5thAnnualCongressoftheEuropeanFederationofInternalMedicine;2005.2

Eurostatstatisticsonhealthandsafety2001.Availablefrom:.TheShockingMortalityofVTEVTEcauses543,454deathinhospitalyearlyMorethancombinedtotalofdeathsfromAIDS,breastcancer,prostaticcarcinomaandtrafficaccidents

AIDS5,860breastcancer

86,831prostaticcarcinoma

63,636trafficaccidents

53,5999.74%ofhospitalizedChinesepatientsdiedfrom

pulmonarythromboembolism(PET)in2006AnUnderestimateBurdenintheWorld10%of

hospitalizedpatientsdiefromPTE175%ofdeadcaseshaveacomplicationofmedicaldisorders217%ofseverehospitalizedpatientsdevelopsymptomatic

DVT375%ofhospitalizedpatientswithacutemedicalillnesshaveabovetwoVTEriskfactors4

1.SandlerDAetal.JRSocMed.1989,82:203-205.2.BaglinTPetal.JClinPathol.1997,50:609-610.3.MismettiPetal.ThrombHaemost.2000,83:14-19.4.AndersonFAetal.JVascSurg.1992,19:557-558TheRiskforVTE

inMedicalHospitalizedPatientsRiskofVTEwithnoprophylaxisinvariousgroupsofhospitalizedpatients

0%

12%22%28～33% 30～50%InternalMedicineAcuteIschemicStroke

ICUAMI1.LeizoroviczandMismetti.Circulation.2004,110(SupplIV):13-19.

2.FraisseF,etal.AmJRespirCritCareMed.2000,161:1109-1114.

3.SpyropoulosAC,etal.Chest.2005,128:958-969.4.CohenAT,etal.ThrombHaemost.2005,94:750-759.59TheIncidenceofVTE

inMedicalHospitalizedPatients1.SamamaMMetal.NEnglJMed.1999,341:79-3800.2.LeizoroviczAetal.Circulation.2004,110:874-879.3.CohenATetal.BMJ.2005,inpress.60fatalPEDVTPre-deathdiagnosiswasmadeinlessthan50%offatalPEAbout80%ofDVT

presentswithasymptomaticTimelyDiagnosisofVTEisVeryImportant1.GoldhaberSZ,etal.AmericanJournalofMedicine1982;73:822-826.2.LethenH,etal.AmericanJournalofCardiology1997;80:1066-1069.3.SandlerDA,etal.J.RoyalSoc.Med.1989;82:203-205.61MedicalHospitalizedPatients

——HighRiskPopulationtoDevelopVTEvenousstasisendothelialinjuryVeryhighriskModerate/highriskLow/moderateriskhypercoaguability62TheIncidenceofPETinChinaTimePETIncidencethecollaborationgrouponPTE-DVTpreventionandtreatmentinChinaVTE-CMEP

studyinChinaVTEinClinicalMedicalElderlyPatients

64DesignofVTE-CMEP0days14-21days90daysAtotalof607acutelyillmedicalhospitalizedelderly

patientswereenrolled1stfollow-up2ndfollow-uplastfollow-upCUS*CUS,VTEeventtelephone,VTEevent*CUS:compressedultrasound65EndPointsofVTE-CMEPPrimaryendpoints(within90day-followupperiod)ObjectivelyverifiedDVTObjectivelyverifiedfatalandnon-fatalPEObjectivelyverifiedasymptomaticDVTSecondaryendpoints(within90day-followupperiod)All-causemortality66BaselineCharacteristicsofthePatients

Heartfailure60.6%Metabolicdisease

42.0%Visceralinflammation29.9%Chronicrenalinsufficiency26.5%Acutecoronarysyndrome24.5%Acutebraininfarction

10.5%Respiratoryfailure10.0%Malignanttumor5.9%VTEhistory3.8%67PrimaryEndPointsofVTE-CMEPPrimaryendpoints（％）9.7%01.534.567.59VTE7.3%2.1%DVTPEDVT+PE0.5%68VTEIncidence

inPatientswithAcuteillnessCOPDwithrespiratoryfailure18.8%Respiratoryfailure16.4%Acutestroke15.6%Acutelyinfectiousdiseases

14.3%Acutecoronarysyndrome8.7%Heartfailure7.6%Acutemyocardialinfarction

4.2%69HistoryofVTE

34.8%Varicosis20.5%ChronicVisceral

Inflammation14.3%Malignanttumour11.1%Obesity

10.7%Chronicrenalinsufficiency8.7%Metabolicdisease

8.2%VTEIncidenceinPatientswithUnderlying

Disorders70Respiratoryfailurewithmechanicalventilation23.5%Centralvenouscatheter

18.9%Permanentpacemaker17.6%VTEIncidenceinPatientsWhoAcceptedTherapeuticMeasures71TheComparisonofVTE-CMEPwiththeInternationalProspectiveStudies0246810121416MEDENOXPREVENTCMEPVTEincidence（％）4.96%14.9%9.7%ARTEMIS10.5%72ThePercentageofVTEHighRiskMedicalPatientsAcceptedProphylaxesTreatmentIMPROVEstudy

39％

of

1,500VTEhighriskmedicalpatientsENDORSEstudy

40％of

37,356VTEhighriskmedicalpatientsCMEPstudyandRAMPstudyinChina

20％

of1,854VTEhighriskmedicalpatients73PharmacologicalandMechanicalProphylaxisTreatmentinVTE-CMEPItems1stfollow-up2ndfollow-uplastfollow-upAnticoagulantsLDUH

13.0%6.0%0.9%LMWH

7.1%3.0%0Warfarin5.4%6.8%4.0%MechanicalProphylaxisCompressionStockings00.3%0.2%Pneumatic

Compression

000LimbMassage04.0%1.4%74VTE-RAMPstudyVTE-RiskAssessmentandProphylaxisTreatmentamongAcute

MedicalPatientsinICU/CCUinChina–Across-sectionalSurvey

75PatientsinICUorCCU

QualifiedfortheEnrollmentCriteriainRAMPCCU(N=704)ICU(N=543)(Total=1247)76ThePercentageofVTERiskFactorsinSevereMedicalHospitalizedPatients99.0%ofpatientsbenefitedfromeffectiveprophylaxesagainstembolism.57.8%

ofpatientshadmultipleVTEriskfactorsThenumberofVTEriskfactorsICU=543CCU=704Total=1247%77ThePercentageofPatientsAcceptedProphylaxisRecommendationsbyACCP

ACCP

recommendationsforseveremedicalpatients

LDUHorLMWHforpatientswhohavenocontraindicationstoanticoagulanttherapyMechanicalprophylaxis(CompressionStockingsorPneumatic

Compression)forpatientswhohavecontraindicationstoanticoagulanttherapy78Epidemiologic

InternationalDay

forthe

EvaluationofPatientsat

RiskofVenousThrombosisintheAcuteHospitalCare

SettingENDORSEstudyTheEnrolledPatientsinENDORSESurgicalpatients(N=30,827)Medicalpatients(N=37,356)(Total=68,183)80Primaryobjectives41.5%atriskforVTEMedicalpatients(n

=37,356

)Secondaryobjectives39.5%receivedprophylaxis64.4%atriskforVTE

58.5

%

receivedprophylaxisSurgicalpatients(n

=30,827

)TheFindingsofENDORSEstudy51.8%atriskforVTE50%

receivedprophylaxisTotal=68,183

81ProportionofSurgicalandMedicalPatientsatHighRiskforVTEWhoReceivedProphylaxis

medicalpatients

surgicalpatients8882665947Hip/kneejointreplacementFractureofhipGastricdiseaseColonicdiseaseUrinarydisease45414025AcuterespiratorydiseaseAcuteheartfailurePulmonaryinfectionIschemicshock0255075100%0255075100%82MechanicalProphylaxisMeasures

TakenbyMedicalPatientsMechanicalprophylaxismeasures:GraduatedCompressionStockings（GCS）Intermittentpneumaticcompression（IPC）Venousfootpump

（VFP）

LacutK,etal.Neurology,2005.65:865-869

GCS+IPC

group4.7%GCSgroup15.9%DVTincidenceafter10-daytreatmentinpatientswithbraininfarction83

PharmacologicProphylaxisMeasures

TakenbyMedicalPatientsLowdoseunfractionatedheparin（LDUH）Lowmolecularweightheparin（LMWH）

MEDENOXPREVENT

PRINCEPRINCE-IIFondaparinuxARTEMIS84BenefitfromAnticoagulantTherapywithHeparin012345RelativeriskHeparinBetterHeparinWorseBelch1981Dahan1986Ibara-Perez1988Bergmann1996Gardlund1996Fraisse1998totalPEMismettiP,etal.ThrombHaemost.2000,83:14-19.RR=0.48[0.34-0.68],P<0.001ANOVA：P=NS85EffectivenessofLMWHComparedwithplacebo,LMWHcanreducetheincidenceofVTEinmedicalhospitalizedpatientssignificantly.

StudiesCasesDrugVTEincidenceOR95%CINNTP

MEDENOX

1102

Enoxaparin

20mg,qd,14days

40mg,qd,14days5.5％0.370.22-0.639<0.001

Placebo14days14.9％

PREVENT

3681

Dalteparin5000IU,qd,14days2.6％0.550.38-0.8045=0.002

Placebo14days5.0％

ARTEMIS

849

Fondparinux

2.5mg,qd,14days1.5％0.530.31-0.92=0.085Placebo14days3.4％NNT:NumberNeededtoTreat86Samamaetal.NEnglJMed.1999,341:793-800ResultsofMEDENOXstudyThebenefitobservedwith40mgofenoxaparinwasmaintainedatthreemonthsTherewasnosignificantdifferenceintheincidenceofVTEbetweenthegroupthatreceived20mgofenoxaparinandtheplacebogroup0481216VTEeventsProximalDVTeventsPlacebo(n=288)Enoxaparin(40mg)(n=291)P=0.037P=0.0002VTEincidence(%)RRR63%RRR65%14.9%5.5%RRR:relativeriskreduction4.9%87ResultsofPREVENTstudyDalteparinreducedtheprimaryendpointseventsby45%onday21

Primaryendpoints：DVT/PE/

suddendeath

Dalteparin（5000IU）PlaceboPrimaryendpoints（％）2.77%4.96%012345P=0.0015LeizoroviczA,etal.Circulation.2004,

110:874-879881.00.502.03.54.0TotalDVTTotalPETotalDeathsTotalMajorBleedingsLMWHbetterUFHbetterRR=1.07(0.79-1.45),p=0.661RR=0.83(0.56-1.24),p=0.37RR=0.74(0.29-1.88),p=0.52RR=0.48(0.23-1.00),p=0.049*RR:

Relativerisk,with95%confidenceintervalLMWHversusUFH89TheRecommendationsofthePreventionforVenousThromboembolisminMedicalHospitalizedPatients——ChineseExpertsWhoNeedtheThromboprophylaxis?Patientsovertheageof40withacutemedicalillnessand/orreducedmobilitywithoneofthefollowingmorbidities:

respiratoryfailure,orCOPDwithacuterespiratoryfailure,orwithmechanicalventilationacuteischemicstrokeacuteinflammatorydiseasesacutecoronarysyndromeheartfailurerheumaticdiseasepreviousVTEvaricosisinflammatoryboweldiseasemalignanttumorobesitychronicrenalfailuremetabolicdiseases(suchasdiabetesmellitus,metabolicsyndrome)centralvenouslinespermanentpacemaker

91HowtoPreventVTEinMedicalPatients?Indicationsofmechanicalthromboprophylaxis

ThepatientswithriskfactorsforVTEwhoarewithoutthecontraindication,anticoagulantthromboprophylaxiscombinedwithmechanicalmethodsshouldbegiven

ThepatientswithriskfactorsforVTEwhoarewiththecontraindicationtoanticoagulants,mechanicalthromboprophylaxisshouldbegiven

Thepatientswithhemorrhagicstrokeorischemicstroke,athighriskofbleedingifanticoagulantsbeused,mechanicalthromboprophylaxisshouldbegivenIfthemechanicalmethodcouldnotbeusedinonesideoflowextremitybecauseofillness,itcanbeusedintheothersideforthromboprophylaxis92ContraindicationstomechanicalthromboprophylaxisSevereischemicatherosclerosisinlowextremityCongestiveheartfailurePulmonaryedemaDVTinlowextremityexceptGCSThromboembolismvenousinflammation

SevereskindiseasesMechanicalThromboprophylaxis93LDUH:

5000U,sctidfor6-14days.Contraindications

toLDUHHemorrhagicdiseaseCoagulationdisordersStaxisaftertraumaoroperationThreatenedabortionMalignanthypertensionBacterialendocarditisAllergytoheparinPharmacologicalThromboprophylaxis94ObservecarefullyonsymptomsandsignsformajorbleedingAdjustLDUHdosebyMonitoringAPTTinhighriskpatientsage≥75yearsrenalinadequacyadvancedcarcinomaMonitorplateletcount,incaseofheparin-inducedthrombocytopenia(HIT)CautionsinLDUHusePharmacologicalThromboprophylaxis95LMWHenoxaparin40mgqdfor6-14daysdalteparin5000Uqdfor6-14daysFondaparinux

2.5mg,qdfor6-14daysContraindications:SeethatofheparinmentionedabovePharmacologicalThromboprophylaxis96TheProcessofThromboprophylaxisinMedicalHospitalizedPatientscontraindications

toanticoagulantsYesNoenoxaparin4000Uqdordalteparin5000UqdorLMWH5000Uq12h,for6-14days*NoYesGCS,IPC,VFPhighrisk?reestimatetheriskInhospitalization*Otherclinicalconditionsshouldbeconsideredwhendeterminingthromboprophylaxisduration97RoutineanticoagulantsprophylaxisforVTEisnotrecommended,becausethecurrenttherapyforAMIhasincludedenoughLDUHandLMWHalthoughthepatientsofAMIareathighriskforVTEThepatientswhoareathigherriskforVTEandwithoutthecontraindicationstoanticoagulants

ThelongerperioduseofLMWHto2weeksmayimprovetheprognosisofthesepatients.

ProphylacticdosegiveninthelongerperioduseofLMWHThecombinationofLMWHwithmechanicalthromboprophylaxisishelpfulin

thesepatients

ThromboprophylaxisforS