会静脉血栓栓塞症

静脉血栓栓塞症： 警惕来自风湿病患者的风险,浙江大学医学院附属第二医院风湿科张婷 吴华香2013-4-21,APS，白塞病,血 栓,栓子脱落,栓 塞,近端DVT约50%并发PE,PE 中80-90%存在DVT,Pesavento R, et al. Minerva Cardioangiol 1997;45:369375Girard P, et al. Chest 1999;116:903908,同一疾病，不同部位、不同阶段,静脉血栓栓塞症(VTE)包括深静脉血栓(DVT)和肺栓塞(PE),DVT和PE年发病率分别为1和0.5；美国每年VTE新发病例超过60万，因此死亡病例数超过29万；英国每年VTE致6万例患者死亡；PE占住院患者死因5-10%,20%,80%,80% 无症状,全球重大健康问题！,静脉血栓栓塞(VTE),风湿性疾病,BD,APS,抗磷脂抗体综合征,白塞病,系统性红斑狼疮,类风湿关节炎,血管炎,ANCA相关性血管炎,其它血管炎,多发性肌炎、皮肌炎,风湿性疾病,治疗药物,非甾体类抗炎药,糖皮质激素,慢作用抗风湿药,生物制剂,其它,其它,APS:抗磷脂抗体综合症BD:白塞病,Ramagopalan et al. BMC Medicine 2011, 9:1,APS是指抗磷脂抗体（aPL）介导的高凝状态，表现为反复静脉和动脉血栓栓塞事件(VTE、ATE)、血小板减少、病态妊娠等；占VTE的4%-14%； 以静脉受累最常见，约50%可出现下肢DVT，还可累及静脉窦、腹腔内静脉、视网膜静脉等少见部位；,抗磷脂抗体综合征(APS),Ortel TL. Thrombosis and the Antiphospholipid Syndrome. Hematology Am Soc Hematol Educ Program. 2005:462-468.Cervera R, Piette JC, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46:1019-1027.Prandoni P, Noventa F, Ghirarduzzi A, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica. 2007;92:199-205,aPL与VTE风险增高相关初次发作VTE后完成6月口服抗凝治疗者： 若aCL阳性，则再发血栓风险29%； 若无抗体，则为14%（P=0.0013）,Schulman S, Svenungsson E, Granqvist S, et al. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Am J Med. 1998;104:332-338.,系统性红斑狼疮(SLE),SLE是一种累及多系统、多器官并有多种自身抗体出现的自身免疫性疾病，其基本病例改变是免疫复合物介导的血管炎。,VTE&ATE风险均增高；10%可出现VTE，可表现为腘静脉血栓（56%）、肺栓塞（22%）和累及深静脉、视网膜静脉、锁骨下静脉和硬脑膜静脉窦的血栓事件（分别为5.6%）； 诊断后5、10年出现VTE的累计风险2.8%、3.7%,Mok CC, Ho LY, Yu KL, et al. Venous thromboembolism in southern Chinese patients with systemic lupus erythematosus. Clin Rheumatol. 2010;29(6):599-604. Tektonidou MD, Laskari K, DB Panagiotakos, et al. Risk Factors for Thrombosis and Primary Thrombosis Prevention in Patients With Systemic Lupus Erythematosus With or Without Antiphospholipid Antibodies. Arthritis Rheum.2009;61(1):29-36.,aPL为确定危险因素：,Risk Factors for Thrombosis and Primary Thrombosis Prevention in Patients With Systemic Lupus Erythematosus With or Without Antiphospholipid Antibodies. Arthritis Rheum.2009;61(1):29-36.,SLE中ATE和VTE发生率因人种而异；1996-2002年，香港，诊断SLE后60个月：,Mok CC, Tang SS, To CH, et al. Incidence and risk factors of thromboembolism in systemic lupus erythematosus: a comparison of three ethnic groups. Arthritis Rheum. 2005;52(9):2774-2782.,中国患者发生VTE较ATE少，但发生VTE比普通人高12倍,Arthritis Rheum. 2005;52(9):2774-2782.,SLE妊娠与VTE风险,Second pregnancy outcomes for women with systemic lupus erythematosus, Ann Rheum Dis 2013;72:547551,VTE, Thrombophilia, Antithrombotic Therapy, and Pregnancy : Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141;e691S-e736S,类风湿关节炎(RA),2006:非心脏血管事件与全身炎症反应相关，ATE、脑血管事件和VTE 30年累计发生率分别为19.6%、21.6%和7.2%；2009:美国国家医院出院调查统计（1975-2005） RA是住院患者发生VTE的危险因素,Liang KP, Liang KV, Matteson EL, et al. Incidence of noncardiac vascular disease in rheumatoid arthritis and relationship to extraarticular disease manifestations. Arthritis Rheum.2006;54(2):642-648.Matta F, Singala R, Yaekoub AY, et al. Risk of venous thromboembolism with rheumatoid arthritis. Thromb Haemost. 2009;101(1):134-138.,2012:Mayo1995-2007,813例RA,平均随访9.6年 vs 对照:累计VTE发生率6.7% vs 2.8% (p=0.005),Bacani AK, Gabriel SE, Crowson CS, et al. Noncardiac vascular disease in rheumatoid arthritis: increase in venous thromboembolic events? Arthritis Rheum.2012;64(1):53-61.,血管炎,血管炎是指一大类以血管的炎症反应为主要病理改变的疾病，包括白塞病、韦格纳肉芽肿（WG）、显微镜下多动脉炎（MPA）、结节性多动脉炎等。部分血管炎与抗中性粒细胞胞浆抗体（ANCA）相关，称之为ANCA相关性血管炎（AAV），包括WG、MPA以及病变局限于肾脏的血管炎等。,血管炎之白塞病(BD),BD患者高达40%可出现血管受累大小动静脉均可累及，以静脉受累多见最常见类型为双下肢DVT，占60-80%此外，还可见下腔静脉栓塞、肺动脉血管瘤、布加综合征、周围动脉的动脉瘤、硬脑膜静脉窦血栓以及腹主动脉动脉瘤等PE较少见,Seyahi E, Yurdakul S. Behets Syndrome and thrombosis. Mediterr J Hematol Infect Dis 2011, 3: e2011026Tomasson G, Monach PA, Merkel PA. Thromboembolic disease in vasculitis. Curr Opin Rheumatol. 2009; 21(1): 4146.,VTE风险增高，且与活动度相关,血管炎之ANCA相关性血管炎(AAV),Merkel PA, Lo GH, Holbrook JT, et al. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegeners Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern Med. 2005; 42:620626.Weidner S, Hafezi-Rachti S, Rupprecht HD. Thromboembolic events as a complication of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2006; 55:146149.Allenbach Y, Pagnoux C, Seror R, et al. Venous thromboembolic events in patients with different systemic necrotizing vasculitides: systematic study of on the French vasculitis study group (FVSG) patient cohort. Arthritis Rheum. 2007; 56:S767Stassen PM, Derks RPH, Kallenberg CGM, et al. Venous thromboembolism in ANCA-associated vasculitisincidence and risk factors. Rheumatology 2008;47:530534.,四项病例对照研究,Stassen PM, Derks RPH, Kallenberg CGM, et al. Venous thromboembolism in ANCA-associated vasculitisincidence and risk factors. Rheumatology 2008;47:530534.,炎症性肌病,多发性肌炎(PM)和皮肌炎(DM)是一组病因不明、以横纹肌为主要病变的非化脓性炎症性肌病，其特点是四肢近端、肩周、颈周、髋周肌群进行性无力；回顾性分析：123例PM和DM患者中，6例共6起新发血栓栓塞事件(6.3%)，均见于活动性DM患者，平均出现于诊断后4.3月；与应用静脉IVIG和高龄等显著相关（p均LMWH利伐沙班,预防,Padua Prediction Score risk assessment model,对于血栓形成风险较高的住院患者，推荐使用LMWH、低剂量普通肝素（LDUH）（每日2次或3次）或璜达肝癸钠这些抗凝药进行血栓预防（1B）对于血栓形成风险较低的住院患者，不推荐使用药物或器械进行血栓预防（1B）对于血栓形成风险较高同时伴有出血且有大出血可能，建议使用分级加压袜（GCS）或间歇充气加压装置（IPC）进行器械血栓预防（2C）,妊娠相关,对于妊娠妇女，推荐低分子量肝素来治疗和预防VTE，而不是普通肝素（1B）对于合并急性VTE的妊娠妇女，建议抗凝药物的使用应至少维持到产后6周（总疗程至少为3个月）（2C）产前24小时：暂停LMWH（1B）,抗凝过程中妊娠，推荐应用LMW