静脉血栓栓塞症危险因素(2012526)

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,静脉血栓栓塞症的危险因素,北京医院呼吸与危重症医学科,许 小 毛,VTE = PTE + DVT,近,50%,腿部近端,DVT,的患者存在,PTE,约,80,PTE,患者有,DVT,（主要是无症状性,DVT,）,Pesavento R,et al,.,Minerva Cardioangiologica.,1997;45:369375,Girard P,et al.,Chest.,1999;116:903908,栓子,迁移,血栓,同一疾病在不同阶段 不同部位的表现,高发病率,高病死率,“多发而少见”,根源：高漏诊率,+,高误诊率,流行病学特点,流行病学资料,Venous thrombosis - 5 million pts yearly,Most caused by inadequate prophylaxis in hospitalized pts,10 % suffer pulmonary embolism 500,000, 1% of all hospitalized pts have PE,Contributes to 5-10 % of all hospital deaths, 125,000 deaths annually from PE,3rd most common cardiovascular cause of death (MI, CVA),Most deaths occur early,流行病学情况,发病率,美国：,DVT 1,，,PTE 0.5,，,年发病60万人,法国：年发病数, 10,万,英国：住院,万/,年,6,深静脉血栓形成,-,肺血栓栓塞症：沉默的杀手,Pulmonary embolism Extrapolated Incidence,7,提高预防意识，有效减少,VTE,Francis CW, N Engl J Med 2007;356:1438-44,警惕,VTE,的发生,VTE,高发病率,-,大部分住院患者都有,1,个或多个,VTE,危险因素,DVT,在许多住院患者中普遍存在,院内获得的,DVT,和,PE,通常无症状,识别,VTE,的危险因素并加以预防，可有效减少,VTE,的发生,PREVENTION IS KEY!,358 hospitals across 32 countries, only 39.5-58.5 % patients at risk of VTE due to medical or surgical causes, respectively, received adequate prophylaxis.,26% of patients with undiagnosed and untreated PE will have a subsequent fatal embolic event, whereas another 26% will have a nonfatal recurrent embolic event,9,Cohen AT, Lancet 2008;371:387394,Qaseem A, Ann Intern Med.2007;146:454-8,Virchows,三要素,Kyrle P A , Eichinger S Blood 2009;114:1138-1139,2009 by American Society of Hematology,Virchows,三要素,Defined VTE Risk Factors: (Virchows Triad),Venous stasis,- CHF, Immobility, Age 70, Travel, Obesity, Recent surgery (,4 weeks) or hospitalization (6 mos),Venous Injury,- Prior DVT/PE, LE Trauma/Surgery,LE trauma or surgery - Very high (50+%),Major surgery - (5 - 8%),Hypercoaguability,- Cancer, Pregnancy, Nephrotic Syndrome, Hyperhomocysteinemia, Factor V Leyden mutation, Deficiency of Protein C/S or ATIII, Anti Phospholipid Ab, HITTS, Smoking,原发性：先天性,遗传变异引起,V,因子突变、蛋白,C,缺乏、蛋白,S,缺乏、抗凝血酶缺乏,继发性,:,后天获得性,骨折、 创伤、 手术、 恶性肿瘤、口服避孕药、制动、高龄、 吸烟 、产妇、 肾病综合征,危险因素,继发性危险因素,原发性危险因素,血栓形成,基因,-,环境相互作用,多数住院患者不止一种危险因素,The incidence of DVT correlates with the total number of risk factors,13,Anderson FA. Circulation 2003;107:I9 I16,临床危险因素识别,原发性,：遗传性、先天性,继发性,环境和人群相关危险因素,外科手术或创伤相关危险因素,内科疾病相关危险因素,医源性干预措施相关因素,14,遗传性易栓症,抗凝蛋白缺乏,抗凝酶、蛋白,C,、蛋白,S,促凝蛋白增加,因子,V Leiden,凝血酶原基因突变,(G20210A),因子,VIII, IX, XI,水平增加,高加索人群遗传性易栓症的发病率,POPULATION PROTEIN C PROTEIN S ANTITHROMBIN FV G20210A,DEFICIENCY DEFICIENCY DEFICIENCY LEIDEN MUTATION,Normal,Consecutive,patients with,first VTE,Relative risk,of first VTE,3,10,3,10,1,25,4,16,4,2,5,DVT,患者中,FV Leiden,突变,*,高加索人群中因子,V Leiden,突变的检出率,37%.,。,APC-R,FV Leiden,DVT,control,DVT,control,Chinese Han nationality,Mainland,(Chu, 1996),5/31,(16%),5/106,(4.7%),0/31,0/141,(Bai, 2000),4/87,(4.6%),0/60,0/87,0/60,Taiwan,(Shen, 1997),0/85,0/85,Chinese Kazak nationality,(Xing, 2001),3/85,(3.5%),Japan,(Zama, 1996),3/33,(9%),0/63,0/29,0/53,Europe,(Koster, 1993),1,(den Heijer, 1996),2,64/301,(21%),1,14/301,(5%),1,47/269,(17.5),2,7/269,(2.6%),2*,DVT,患者中凝血酶原基因,G20210A,突变,*,高加索人群中凝血酶原,G20210A,突变约占,2%,。,Prothrombin gene G20210A mutation,DVT,control,China,(Bai, 2000),0/98,0/100,(He, 2002),0/103,0/106,UK,(Cumming, 1997),12/219,(5.5%),2/164,(1.2%),Holland,(Poort, 1996),18%,1%,*,DVT,患者中抗凝蛋白缺乏,n,Deficient proteins,AT,PC,PS,Total,China,Mainland,(Bai, 2000),87,5,(5.7%),8,(9.2%),13,(14.9%),26,(29.9%),Taiwan,(Shen, 1997),85,3,(3.5%),16,(18.8%),28,(32.9%),47,(55.3%),Hong kong,(Liu, 1994),52,5,(9.6%),9,(17.3%),10,(19.2%),24,(46.1%),Japan,(Suehisa, 2001,113,2,(1.8%),9,(8.0%),20,(17.7%),31,(27.4%),Europe,(den Heijer, 1996),269,10,(3.7%),15,(5.6%),7,(2.6%),32,(11.9%),抗凝蛋白,缺乏,其他,/,未明,APC-R,(Genetic defect?),APC-R,(FV Leiden),中国汉族人群,高加索人群,其他,/,未明,抗凝蛋白,缺乏,何时怀疑遗传性易栓症,VTE,家族史,发病年龄,70,岁,妊娠期和产褥期,肥胖,24,长时间制动引起下肢静脉血液淤积，饮水减少导致血液粘稠度增加,活动减少、肌张力减低、疾病增加、血管内皮功能减弱、下肢静脉回,流障碍、多种凝血因子活性增强,Incidence of VTE by sex and age,British Journal of HaematologyVolume 139, Issue 2, pages 289-296, 25 SEP 2007 DOI: 10.1111/j.1365-2141.2007.06780.x :/onlinelibrary.wiley/doi/10.1111/j.1365-2141.2007.06780.x/full#f1,Incidence of VTE by obesity,The risk of venous thrombosis: obesity and travel,MEGA study overall 2 fold increase in risk,Cannegieter SC et al. PLOS Medicine 2006;3 (8):1258-1264.,预防,-ACCP9,版指南,长途旅行者,对于有,VTE,危险因素的旅行者（既往,VTE,病史、近期创伤或手术史、肿瘤、妊娠、应用雌激素、高龄、活动不便、重度肥胖、或已知易栓症者），建议旅行期间经常活动、做腓肠肌运动或尽可能坐过道的座位（,2C,级）,，或,/,和,建议应用膝下梯度弹力袜,GCS,，维持踝部压力,15-30mmHg,之间,(2C,级,),。,28,外科手术或创伤相关危险因素,麻醉时间,30,分钟,髋、膝关节置换术,泌尿系统手术,神经外科手术,妇产科手术,严重创伤,骨折、脊髓损伤、头颅损伤,29,手术对组织、血管壁的损伤导致凝血系统激活，麻醉、体外循环造成血流缓慢、输血引起血液粘稠度增加,住院患者发生,DVT,的风险,Patient Group DVT Prevalence %,Medical patients:1020,General surgery:1540,Major gynecologic surgery:1540,Major urologic surgery:1540,Neurosurgery:1540,Stroke:2050,Hip or knee arthroplasty: 4060,Major trauma:4080,Critical care patients:1080,骨科大手术后,VTE,发生率较高,术式,DVT (%),PE (%),总发生率,近端发生率,总发生率,致命性,%,THR,42-57,18-36,0.9-28,0.1-2.0,TKR,41-85,5-22,1.5-10,0.1-1.7,髋骨骨折,46-60,23-30,3-11,0.3-7.5,参考文献,:,静脉血栓栓塞,（,VTE,，,venous thromboembolism,）,的预防，第,8,版,ACCP,指南,. Chest 2008; 133:381-453,中国,3,个中心,马来西亚,1,个中心,台湾,4,个中心,南韩,5,个中心,菲律宾,3,个中心,泰国,1,个中心,印度尼西亚,2,个中心,AIDA,研究：,7,个国家,19,个中心进行的研究，发表于,2005,年,每个国家地区入组的病例数,中国,51,12.5,印度尼西亚,21,5.2,韩国,122,30.0,马来西亚,30,7.4,菲律宾,60,14.7,台湾省,83,20.4,泰国,40,9.8,总例数,407,DVT,发病率,43.2%,%,%,%DVT,(N=295),总,DVT (%),58.1%,25.6%,42.0%,AIDA:,不同类型的骨科手术后均会发生,DVT,Piovella,et al. J Thromb Haemost,2005,事件发生率,%,普外手术,THR,TKR,髋部骨折,亚洲研究,西方研究,手术后,DVT,的发生率,0,40,60,80,100,20,Geerts,et al. Chest,2004;,Leizorovicz,et al,.,Int J Angiol,2004; Piovella,et al,.,J Thromb Haemost,2005,骨科大手术患者,VTE,的危险分度,危险度,判断指标,低度危险,手术时间,45,40,岁,无危险因素,中度危险,手术时间,45,有危险因素,手术时间,45,40,岁,无危险因素,高度危险,手术时间,45,60,岁 有危险因素,手术时间,45,4060,岁,有危险因素,极 高 危,骨科大手术 重度创伤 脊髓损伤,手术时间,45,40,岁,有多项危险因素,预防,-ACCP 9,版指南,对于进行重大骨科手术患者，建议血栓预防措施延长至术后,35,天，而不仅仅是,10-14,天（,2B,级）。,对于住院期间的重大骨科手术患者，建议抗血栓药物和,IPCD,联合应用（,2C,级）。,38,内科疾病相关危险因素,心功能不全、急性心梗,COPD,、,ARDS,、间质性肺疾病,肾病综合征,恶性肿瘤,急性感染,结缔组织疾病,内科疾病急性期住院患者,VTE,发生较一般人群增加,8,倍,39,肿瘤与,VTE,40,41,预防,-ACCP 9,版指南,内科,急症,和危重症,患者,对于血栓形成风险较高的内科急症患者，推荐预防性抗凝治疗（,1B,级）。,对于血栓形成风险较高，但目前正出血或有较高出血风险的内科急症患者，建议选择机械性预防措施（,2C,级）。当出血风险减少，但,VTE,风险持续存在时，建议应用药物预防替代机械性预防（,2B,级）,对于开始血栓预防治疗的内科急症患者，疗程不应超过患者卧床或住院时间（,2B,级）。,42,肿瘤患者,对于无,VTE,危险因素（既往血栓栓塞病史、卧床、激素治疗、服用血管再生抑制剂及镇静剂）的患者，不建议常规预防血栓,治疗,（,2B,级）,。,对于有,VTE,危险因素且出血风险较低的实体肿瘤患者，建议应用,LMWH,或,LDUH,预防血栓（,2B,级）。,对于留置中心静脉导管的肿瘤患者，不建议常规预防血栓,治疗,（,2B,级）,。,43,医源性干预措施相关因素,药源性,抗肿瘤药,口服避孕药,2-3/,万，未用万,激素替代疗法,2-4,倍,导管相关性,44,VTE,风险评估,DVT wells,评分,PE wells,评分,日内瓦评分,VTE,风险评分（,Caprini,模型）,45,Wells Criteria (DVT),Wells Criteria (DVT),Active cancer (tx within 6 mos or palliative care) (1),Calf swelling (3 cm difference 10 cm below tib tub) (1),Collateral superficial veins (1),Paralysis, paresis, or recent immobilization LE (1),Pitting edema confined to involved leg (1),Bedridden within 3 days or surgery w/anesth 3cm, erythema, pitting edema affected leg only),+3,PE Is #1 Diagnosis, or Equally Likely,+3,Heart Rate 100,+1.5,Immobilization at least 3 days, or Surgery in the Previous 4 weeks,+1.5,Previous, objectively diagnosed PE or DVT?,+1.5,Hemoptysis,+1,Malignancy w/Rx within 6 mo, or palliative?,+1,2: Low 2 to 6: Moderate 6: High,Adapted with permission from Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, et al. Derivation of a simple,clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED d-dimer.,Thromb Haemost 2000;83:416-20.,Am J Med 2002;113:270,Revised Geneva score,48,Torbicki A. European Heart Journal (2008) 29, 22762315,Caprini Risk Assessment Model,49,Bahl V,Ann Surg 2009. EpubSeptember 22,Caprini Risk Assessment Model,风险因素总分,风险等级,DVT发生率,推荐预防方案,0-1,低危,10%,早期活动,2,中危,10-20%,药物预防或物理预防,3-4,高危,20-40%,药物预防和或物理预防,5,极高危,DVT发生率40-80%，死亡率1-5%,药物预防和物理预防,50,51,K Deatrick, Phlebology 2010;25:296311,E-Alerts Can Increase Prophylaxis,2506 hospitalized patients,VTE risk score 4,Randomized to intervention or control,Intervention,Treatment Received,Mechanical, %,Pharmacologic, %,E-Alert,10,23.6,Control,1.5,13,P,-value,0.001,0.001,Kucher N, et al.,N Engl J Med,. 2005;352:969-977.,major risk factors of cancer, prior VTE,and hypercoagulability were assigned a score of 3;,the intermediate risk factor of major surgery was assigned a score of 2;,and the minor risk factors of advanced age, obesity, bed rest, and the use of hormone-replacement therapy or oral contraceptives were assigned a score of 1.,53,Kucher N, et al.,N Engl J Med,. 2005;352:969-977.,Intervention,Control,Time,(,days,),0,30,60,90,% Freedom from DVT/,PE,90,92,94,96,98,100,E-Alerts Decrease VTE,Kucher N, et al.,N Engl J Med,.,2005;352:969-977.,Intervention,Control,N,umber,at risk,1255,977,900,1251,976,893,839,853,41%,P,Effectiveness can wane over time,Lecumberri R, et al.,Thromb Haemost.,2008;100:699-704.,*,P ,*,56,祈予指正！,