内科病人静脉血栓栓塞性疾病李小鹰

内科病人静脉血栓栓塞性疾病李小鹰全面认识VTE全球VTE的发生率居高不下VTE是患者死亡的主要因素VTE带来沉重的负荷多数VTE的发生与入院时存在的基础疾病和手术情况相关院内或院外适宜的静脉血栓预防可降低VTE所带来的危害。VTE是可预防的严峻的公共卫生保健问题1CohenAT.Presentedatthe5thAnnualCongressoftheEuropeanFederationofInternalMedicine;2005.2Eurostatstatisticsonhealthandsafety2001.Availablefrom:.VTE所致死亡触目惊心VTE所导致的死亡例数:543,4541

（2005第5欧盟内科年会）VTE所致死亡超过了以下原因所致死亡的总数:AIDS

5,8602乳腺癌 86,8312前列腺癌 63,6362交通事故 53,59922006年中国住院患者PTE死亡率达9.74%内科患者VTE：一个被低估的全球疾病负担住院人群统计，死亡者中10%死于PTE1PTE死亡者中，75%合并有内科疾病2住院期间17%的重症患者发生症状性DVT375%的内科重症患者存在2个以上VTE的危险因素41.SandlerDAetal.JRSocMed1989;82:203-5.2.BaglinTPetal.JClinPathol1997;50:609–10.3.MismettiPetal.ThrombHaemost2000;83:14–9.4.AndersonFAetal.JVascSurg1992;19:557-8内科住院患者VTE患病率未经治疗时DVT的危险性

0%

12%22%28～33% 30～50%内科脑卒中偏瘫

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.内科住院患者VTE患病率国外前瞻性研究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病例在死亡前得到诊断的不足一半

1约80%DVT病例无临床表现2,3VTE经常得不到及时诊断1.GoldhaberSZ,etal.AmericanJournalofMedicine1982;73:822-826.2.LethenH,etal.AmericanJournalofCardiology1997;80:1066-1069.3.SandlerDA,etal.J.RoyalSoc.Med.1989;82:203-205.住院接受内科治疗的患者属于VTE高危人群静脉血流缓慢血管内皮受损极高危中/高危低/中危高凝状态中国PTE发病并不少见全国PTE-DVT形成防治协作组报道的PTE病例数（年）

老年内科住院患者VTE事件发生率调查VTEinClinicalMedicalElderlyPatients

(VTE-CMEP)VTE-CMEP研究VTE-CMEP

研究方案0天14-21天90天入选老年内科急症住院患者607例首次随访CUS二次随访VTE事件，CUS三次随访电话VTE事件VTE-CMEP

主要终点事件主要终点事件90天内客观检查证实的DVT；90天内客观检查证实的致死性或非致死性PE；客观检查证实的无症状的DVT。次要终点事件90天内全因死亡。

入选患者基础疾病情况%心力衰竭60.6%代谢性疾病42.0%内脏炎症29.9%慢性肾功能不全26.5%急性冠脉综合症24.5%急性脑梗塞10.5%呼吸衰竭10.0%恶性肿瘤5.9%VTE病史3.8%VTE-CMEP

主要终点事件主要终点患病率（％）9.7%01.534.567.59VTE事件7.3%2.1%DVTPEDVT+PE0.5%内科急症不同患者VTE的发生率COPD伴急性呼吸衰竭18.8%呼吸衰竭16.4%急性脑梗塞15.6%急性感染性疾病14.3%急性冠脉综合症8.7%心力衰竭7.6%急性心肌梗死4.2%不同基础疾病VTE发生率VTE史34.8%静脉曲张20.5%慢性内脏炎症疾病14.3%恶性肿瘤11.1%肥胖10.7%慢性肾功能不全8.7%代谢疾病8.2%不同治疗措施患者VTE发生率

呼吸衰竭伴机械通气23.5%中心静脉导管18.9%永久性起搏器17.6%VTE–CMEP与其他研究结果比较0246810121416MEDENOXPREVENTCMEPVTE发病率（％）4.96%14.9%9.7%ARTEMIS10.5%内科高危患者接受VTE预防不足IMPROVE研究：1500例内科高危患者39％ENDORSE研究：

37356例内科高危患者40％国内（CMEP与RAMP）研究

1854例内科高危患者20％VTE-CMEP研究预防VTE治疗情况

项目首次随访二次随访末次随访抗凝药物普通肝素13.0%6.0%0.9%低分子肝素7.1%3.0%0华法令5.4%6.8%4.0%机械性预防弹力袜00.3%0.2%下肢循环驱动器000肢体按摩04.0%1.4%VTE-RAMP研究

ICU/CCU内科急症住院患者VTE风险评估和预防治疗现况调查（VTE—RiskAssessmentandProphylaxisTreatmentamongAcute

MedicalPatientsinICU/CCUinChina–Across-sectionalSurvey）

ICUvsCCU

符合标准病人入组情况(

N

=

1247

)CCU(N=704)ICU(N=543)内科重症患者VTE危险因素比例

评估的患者中，有99.0%的患者采用血栓预防治疗后受益的证据，其中57.8%患者有多重危险因素危险因素个数接受ACCP指南推荐的预防措施的比例**ACCP指南推荐的内科重症患者的预防方法包括：无药物预防禁忌患者使用普通肝素或低分子肝素;有药物预防禁忌患者使用机械预防方法（弹力袜或充气加压装置）ENDORSE研究-----急症住院VTE危险患者流行病学国际评估研究ENDORSE-Epidemiologic

InterNationalDay

forthe

EvaluatiOnofPatientsat

RiskofVenousThrombosisintheAcuteHospitalCare

Setting外科及内科患者所占比例(

N

=

68,183

)外科患者(N=30,827)内科患者(N=37,356)主要研究目的42

%

存在VTE危险内科患者(

n

=

37,356

)次要研究目的40

%

接受了

ACCP

治疗推荐64

%

存在VTE危险59

%

接受了ACCP

推荐治疗外科患者(n

=30,827

)内科VTE高危并接受推荐预防治疗的患者52

%

存在VTE危险50

%

接受了ACCP

推荐治疗总计(

N=68,183

)内外科VTE高危患者接受推荐预防治疗情况

外科患者内科患者8882665947髋/膝关节置换髋部骨折胃部疾病结肠疾病泌尿系统疾病45414025急性呼吸系统疾病急性心衰肺部感染缺血性卒中0255075100%0255075100%内科住院患者VTE机械性预防

机械性预防措施分级加压弹力袜（GCS）间歇充气加压泵（IPC）足底静脉泵（VFP）缺血性脑卒中患者应用10d后经超声诊断的DVT发生率GCS+IPC预防组为4.7%单用GCS预防组为15.9%

LacutK,etal.Neurology,2005.65:865-869

内科VTE药物预防疗效

低剂量普通肝素（LDUH）低分子肝素（LMWH）

MEDENOXPREVENT

PRINCEPRINCE-II磺达肝癸钠

ARTEMIS使用肝素进行血栓预防治疗可显著获益012345相对危险性肝素较好肝素较差Belch1981Dahan1986Ibara-Perez1988Bergmann1996Gardlund1996Fraisse1998总PEMismettiP,etal.ThrombHaemost2000;83:14-19.RR=0.48[0.34-0.68],P<0.001方差分析：P=NS低分子肝素杰出的疗效进一步被证实几项较大的研究结果显示，低分子肝素预防内科住院患者VTE显著优于安慰剂研究病例数药物治疗VTE发病率OR95%CINNTP

MEDENOX1102依诺肝素20mg,qd,14天

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

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

ARTEMIS

849Fondparinux2.5mg,qd,14天1.5％0.530.31-0.92=0.085安慰剂3.4％NNT:每挽救1例VTE所需要治疗的病人数0481216所有静脉栓塞事件所有近端的深静脉血栓事件安慰剂(n=288)依诺肝素40mg(n=291)P=0.037P=0.0002NS患者(%)DVT,深静脉血栓;PE,肺栓塞NS,无显著意义;VTE,静脉血栓栓塞;RRR,相对风险降低RRR63%依诺肝素4000AXaIU使近端DVT风险降低65％，

此益处在3个月随访时仍然存在RRR65%14天治疗期间的静脉血栓栓塞性事件：Medenox研究：患者随机分组，分别接受依诺肝素20毫克或依诺肝素40毫克治疗，或者给予安慰剂，接受依诺肝素20mg治疗的患者与接受安慰剂治疗的患者相比，其预后没有显示显著差异。Samamaetal.Acomparisonofenoxaparinwithplaceboforthepreventionofvenousthromboembolisminacutelyillmedicalpatients.ProphylaxisinMedicalPatientswithEnoxaparinStudyGroup.NEnglJMed1999;341:793-800

MEDENOX研究

PREVENT研究结果

21天时，达肝素（法安明）显著降低主要终点发生率达

45％

主要终点：DVT/PE/猝死法安明5000IU组安慰剂组主要终点发病率（％）2.77%4.96%01234545％P=0.0015LeizoroviczA,etal.Circulation2004;110:874-879.内科治疗病人预防静脉血栓形成依诺肝素是唯一一种LMWH已经在国内外注册用于预防内科治疗患者的静脉血栓形成MEDENOXn=11021PRINCEn=4512PRINCEIIn=20630246810121416VTE;第1-14天(%)P<0.001024681012VTE(%)024681012141618VTE(%)0510152025303540VTE(%)P=0.015等效性检验AP=0.014等效性检验AP=0.044依诺肝素40mg(4000IU抗Xa)qd依诺肝素20mg(2000IU抗Xa)qd安慰剂qd肝素钙5000IUs.c.tidVTE,venousthromboemboliceventsLMWH,low-molecular-weightheparin1.SamamaMM,etal.NEnglJMed1999;341:793-800.2.Kleberetal.ThrombHaemost1999;(suppl)1552.3.Kleberetal.UnpublishedDataA.等效性检验：两种治疗等效，等效的定义是两组的最大差异为4%低分子肝素与普通肝素疗效比较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相对危险性MismettiP,etal.ThrombHaemost2000;83:14-19.内科住院患者静脉血栓栓塞症预防中国专家建议写作组

中华医学会老年医学分会

中华医学会呼吸病学分会

中华老年医学杂志编辑委员会

中华结核和呼吸杂志编辑委员会

——中华老年医学杂志中华呼吸结核杂志2009年第一期内科住院患者静脉血栓栓塞症预防中国专家建议中国专家建议预防性治疗的指征与方法一、需要进行VTE预防性治疗的内科患者二、VTE预防性治疗的方法（一）机械性预防措施（二）药物预防性治疗三、一些特殊临床情况下的VTE预防性治疗１、急性心肌梗死２、急性脑卒中３、重症监护病房（ICU）患者４、恶性肿瘤５、肾功能不全四、几点说明需要进行VTE预防性治疗的内科患者Foracutelyillmedicalpatientsadmittedtohospitalwithcongestiveheartfailure

orsevererespiratorydisease

or

whoareconfinedtobedandhaveoneormoreadditionalriskfactorsactivecancer,previousVTE,sepsis,acuteneurologicdisease,orinflammatoryboweldisease

——ACCP8thEditionguidelines需要进行VTE预防性治疗的内科患者

国内专家建议

40岁以上因急性内科疾病住院患者，和卧床≥3d，同时合并下列病症或危险因素之一呼吸衰竭、COPD急性加重、急性脑梗死、心力衰竭（NYHAⅢ或Ⅳ级）、急性感染性疾病（重症感染或感染中毒症）、急性冠状动脉综合征、VTE病史、恶性肿瘤、炎性肠病、慢性肾脏疾病、下肢静脉曲张、肥胖（体重指数＞30kg／m２）及高龄（年龄≥75岁）。VTE预防性治疗的方法机械性预防措施适应证无机械预防性治疗禁忌证的VTE高危患者，建议与药物预防联合应用对抗凝药物治疗有禁忌证的VTE高危患者出血性脑卒中或缺血性脑卒中，抗凝治疗弊大于利的患者患肢无法或不宜应用机械性预防措施者可在对侧实施预防VTE预防性治疗的方法机械性预防措施禁忌证严重下肢动脉硬化性缺血充血性心力衰竭肺水肿下肢DVT（GCS除外）血栓性静脉炎下肢局部严重病变（皮炎、坏疽、近期手术及严重畸形）VTE预防性治疗的方法药物预防性治疗单独应用阿司匹林无助于预防VTELDUH方法：5000U，SC，1次／12h，6-14d禁忌证:出血性疾病凝血功能障碍外伤与术后渗血先兆流产恶性高血压细菌性心内膜炎对肝素过敏者VTE预防性治疗的方法LDUH应用中需要特别重视的几个问题密切观察出血并发症和严重出血危险发生出血，立即停用肝素，可静脉注射硫酸鱼精蛋白（1mg／100U肝素）对高危人群监测APTT以调整剂量年龄≥75岁肾功能不全进展期肿瘤监测血小板计数，警惕HITVTE预防性治疗的方法LMWH使用方法依诺肝素40mg，1次／d达肝素5000U，1次／d疗程：6-14d禁忌证对LMWH过敏其余禁忌证同普通肝素磺达肝癸钠2.5mg，1次／d，建议治疗6～14d住院患者血栓预防治疗流程患者是否属于高危人群是患者是否无法接受药物性血栓预防开始血栓预防治疗：法安明5000IU/依诺肝素4000IU1/d或普通肝素5000IU1/12h血栓预防治疗一般需要维持6-14天，同时应考虑其他临床因素或住院时间的长短以确定血栓预防的疗程随着病情的变化，对可能导致静脉血栓栓塞性疾病的危险因素进行重新评估考虑非药物血栓预防方法如弹力袜，间歇式气压治疗仪，足底泵否否是一些特殊临床情况下VTE预防性治疗急性心肌梗死（AMI）无需常规用药预防VTE经评估VTE高危的AMI患者如无禁忌证，可延长LMWH治疗时间至２周延长治疗期间改为预防剂量可联合使用机械性预防措施一些特殊临床情况下VTE预防性治疗急性脑卒中缺血性脑卒中无禁忌证，给予LDUH或LMWH用药前必须仔细权衡血栓和出血的风险建议联合机械性预防措施预防VTE出血性脑卒中如无禁忌证，应使用机械性预防措施预防VTE一些特殊临床情况下VTE预防性治疗ICU患者无禁忌证，使用LDUH或LMWH进行预防，并建议联合应用机械方法预防VTE；有高出血风险的患者，先采取GCS和（或）IPC预防血栓直至出血风险降低，然后用药物代替机械方法预防血栓，或药物与机械方法联合应用；对药物和机械预防措施均有禁忌证的患者，应加强临床监护和床旁超声检查，以尽早发现和治疗VTE一些特殊临床情况下VTE预防性治疗恶性肿瘤因内科急症住院的VTE高危恶性肿瘤患者，建议常规给予血栓预防性治疗行化疗或糖皮质激素治疗的恶性肿瘤患者，不建议常规使用血栓预防性治疗进展期乳腺癌接受化疗者，可考虑应用低剂量华法林预防性治疗置有中心静脉导管的恶性肿瘤患者，不推荐常规使用药物预防血栓形成一些特殊临床情况下VTE预防性治疗肾功能不全对严重肾功能不全的患者，建议选择LDUH作为预防性抗凝治疗的药物肌酐清除率＜30ml／min的患者，如选择LMWH，建议减量使用应用LMWH时，如有条件，建议每1～2天监测凝血因子Xa水平，据此调整剂附一：肝素诱导的血小板减少症(略)附二：内科患者静脉血栓栓塞症治疗原则(略)谢谢！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