杨仁池 血友病防治的进展课件

血友病防治的进展 中国医学科学院中国协和医科大学 血液学研究所血液病医院 杨仁池 概况 n血友病是一种遗传性出血性疾病，呈X连锁隐 性遗传。本病是由于凝血因子VIII和IX基因突 变使FVIII和FIX质或量的异常所致。 n血友病甲在男性人群中的患病率约为1/5000， 占血友病总数的80%以上；血友病乙在男性人 群中的患病率约为1/30000，占血友病总数的 10%20%。 n目前，本病在发展中国家（如我国）的致残率 和病死率远高于发达国家。替代治疗是唯一有 效的治疗措施。因此，这类患者也是发生肝炎 和爱滋病的高危人群。 血友病的严重程度与出血 血友病甲和乙的分型 重型 中间型 轻型 因子水平 5 % 特征是自发出血轻微损伤出血严重损伤、外科手术 和侵入性检查时出血 每周可出血 1- 2次每月可出血 1次可以从不出血 关节受累为特征可有关节受累关节受累罕见 (关节血肿) 国内现状 n无足够的凝血因子制剂 n凝血因子制剂费用太高 n大多数血友病病人无医疗保险 n无全国性的血友病防治系统 n病人组织未获官方认可 n医护人员对本病认识不够 n病人及其家庭成员对本病认识不够 n多数医院不能对本病进行诊断（因为实验条件不 具备） WFH Global Survey 2001/2 Country Pop. Diagnosed No. HTC Percapita (106) (%) FVIII use Australia 19 95 15 3.0 USA 278 87 140 3.4 Germany 82 82 6 5.5 Iran 63 82 10 0.5 Russia 146 81 4 0.1 Egypt 63 75 7 0.1 South Africa 42 52 10 0.6 India 998 12 56 0.01 China 1227 5 WFH Global Survey 2004 nAustralia: Hemophilia 1070, vWD 804 nUSA: Hemophilia 14886, vWD 9801 nUK: Hemophilia 6109, vWD 5582 nGermany: Hemophilia 4800, vWD 3100 nItaly: Hemophilia 5319, vWD 2275 nRussia: Hemophilia 7875, vWD 3380 nThailand: Hemophilia 1325, vWD 69 nTurkey: Hemophilia 1929, vWD 100 nSouth Africa: Hemophilia 1579, vWD 463 nChina: Hemophilia 4131, vWD 227 WFH Global Survey 2004 n调查的国家：96个 n覆盖的世界人口：85% n血友病：120812例；vWD：43334例 n国家数据库：40个 Current Data nTianjin Hemophilia Center:1627 nAnhui Hemophilia Center: 717 nShandong Hemophilia Center: 669 nJiangsu Hematology Institute: 389 nRuijin Hospital: 341 nFirst affiliated hospital of Sun Yet-san University: 250 nNanfang Hospital: 169 nGuangdong peoples hospital: 165 nPeking Union College Hospital: 79 nThe third peoples hospital of Wenzhou: 60 nBeijing Peoples Hospital: 55 nBeijing children hospital: 47 nFirst affiliated hospital of Zhejiang University: 9 nTotal: 4577 Hemophilia and related disorders in Tianjin Hemophilia Center (1980-2002.6) nTotal:1312 nHemophilia A: 988 (75.3%) nHemophilia B: 186 (14.2%) nvWD：85 (6.5%) nFXI deficiency：23 (1.8%) nAcquired FVIII deficiency：15 (1.1%) nOthers：15 (1.1%) Arthropathy in different ages n0-10: 48/386(12.4%) (15.2%) n10-20: 76/251(30 .3%)(35.0%) n20-30: 73/141(51 .8%)(55.7%) n30: 74/143(51 .7%)(72.3%) AIDS in recipient of coagulation factor concentrates (1978-85) n60-70% patients became infected with HIV nThousands of them have died of AIDS nHIV infection increases the risk of liver failure after infection with HCV 21-fold (Estimated risk of liver failure 20 years after infection with HCV is 10%) 血友病的基因治疗 n世界上首例血友病基因治疗临床试验由薛 京伦教授及其研究组完成 nFVIII或FIX基因缺陷小鼠的实验 nFVIII或FIX基因缺陷犬的实验 n现阶段的临床试验： 载体-AAV、腺病毒、逆转录病毒等 途径-肌肉注射、肝静脉等 血友病出血的治疗原则 早期治疗 - 2小时以内, 如有可能进行“家庭”治疗 “怀疑时治疗” 静脉穿刺时倍加小心 - 合适的针头 (21 - 25G) - 恰当的技术 - 穿刺后加压 10 - 15 分钟 避免导致血小板功能异常的药物 ( 阿斯匹林 / NSAID) 多学科方法 “综合护理” 血友病的出血部位 关节 肌肉 / 软组织 口腔 鼻衄 血尿 胃肠道 擦伤 / 撕裂伤 中枢神经系统出血 损伤相关 任何部位 替代治疗指南 出血类型FVIII剂量（U/kg）FIX剂量（U/kg）因子水平(%) 急性关节出血10-20，q.12h15, q.2430-50 肌肉内20-30, q12h40-60, q.24h40-50 CNS50, q12h, 或连续输注100，然后50, q24h开始100，然后 50-100，10-14d 损伤或外科50, q12h, 或连续输注100, q24h100, 然后50, 至伤口开始愈合， 然后30至痊愈 咽后壁50, q12h, 4d40, q24h, 4d50-70 胃肠道50, q12h, 3d, 40, q24h, 3d50-100 或直至出血减轻或直至出血减轻 血尿40，3-5d40, 3d50 拔牙20,一次，EACA40,一次，EACA50 100mg/kg, 7-10d100mg/kg, 7-10d 腹膜后50, q12h, 6d100, q24h, 6d开始100，然后 50，直至痊愈 China A Prioritized Project, WFH n1993 1997: Education and Training n1997 2001/02: Hemophilia Twinning Centres and Treatment Centre Development n2002 2004: A Country Program with a Hemophilia Treatment Centre Network, China China A Prioritized Project, WFH In 1993, WFH launched a priority project to promote and improve Hemophilia Care in China. Objectives: Education Training Awareness Care improvements Over the past 10 years significant progress has been Achieved through three phases of planning. 1993 1997: Education and Training Major activities focused on Hemophilia conferences for educating professionals, patients, families and hospital staff. Training, education, awareness and participation by patient groups increased. WFH fellowships were awarded to physicians, nurses, technologists and surgeons. This resulted in increased professionals with expertise in the clinics. 1997 2001/02: Hemophilia Twinning Centres and Treatment Centre Development Under the WFH Hemophilia Twinning Centre program, 4 centres were established in China. 1997Hematology Institute, Tianjin / Calgary, Canada 2000Nanfang Hospital, Guangzhou / Ottawa, Canada 2000 Hong Kong/ London, UK 2001Ruijin Hospital, Shanghai / Calgary and Ottawa Hemophilia Treatment Centres were developed in Jinan and Hefei. Patient Group Activities / Leadership Five patient leaders from four cities were identified and received leadership training in Montreal (2000) , Seville (2002) and Bangkok (2004). This group established the Hemophilia Home of China developing a website. They have been very active in their communities promoting patient care and participation. Many patient education materials have been translated into Chinese by this group. Vision for a National Strategy 2001 - 2004 As these centres matured, sharing of expertise and resources strengthened. Through this collaboration, the value of a National Body to coordinate development of Hemophilia Care in the country was realized. At the Regional Hemophilia Care Conference, At the Regional Hemophilia Care Conference, Guangzhou, Nov 2001, the professional Guangzhou, Nov 2001, the professional groups agreed on: groups agreed on: (1) Three priority projects for urgent (1) Three priority projects for urgent development: development: (i) A National Registry (i) A National Registry (ii) Hemophilia Nursing (ii) Hemophilia Nursing (iii) Coagulation testing workshops(iii) Coagulation testing workshops. . (2) A strategy to formulate a National Body, (2) A strategy to formulate a National Body, laterlater formalized as the “Hemophilia formalized as the “Hemophilia Treatment Centre Collaborative Network, Treatment Centre Collaborative Network, China”.China”. Project Progress National Registry Project chair: Dr. Renchi Yang, Tianjin. Established 2002. Current registrants = 4132 patients (approx. %5 of estimated PWH in China). Poster presentation in Bangkok. Hemophilia Nursing Project Chair: Dr. Jing Sun, Nanfang. Two Hemophilia Nursing conferences November 2003, October 2004. Poster presentation in Bangkok. Coagulation Testing Workshop Project Chair: Dr. Xuefeng Wang, Shanghai, April 2005 2002 2004: A Country Program with a Hemophilia Treatment Centre Network, China Between 2002 2003 Dr. MC Poon and Dr. KH Luke visited centres in Beijing, Tianjin, Jinan, Shanghai, Hefei and Guangzhou and received unanimous support for a National Network. A proposal for a Country Program for China was supported by WFH. A WFH Hemophilia Conference was held to establish the network in 2004 in Shangdong Blood Center, Jinan, Shangdong. WFH Hemophilia Conference March 2004, Jinan, China At this conference the Hemophilia Treatment Centre Collaborative Network China was formalized. The six founding members are: 1. Hemophilia Centre, Institution of Hematology, Tianjin 2. Hemophilia Centre, Nanfang Hospital, Guangzhou 3. Hemophilia Centre, Ruijin Hospital, Shanghai 4. Hemophilia Centre, Peking Union Medical College Hospital, Beijing 5. Hemophilia Centre, Anhui Provincial Hospital, Hefei 6. Hemophilia Clinic, Shandong Blood Centre, Jinan A great achievement was the vast representation of 150 professionals from 25 cities / provinces. A NETWORK OF HEMOPHILIA TREATMENT CENTRES HAS BEEN ESTABLISHED AS A SOLID FOUNDATION TO PROMOTE HEMOPHILIA CARE IN CHINA FOR THE FUTURE. Challenges Ahead MAJOR TARGETS 1. Provide accessible care to more patients with Hemophilia Outreach programs Education Workshops Hemophilia Nursing Patient group leaders / activities 2. Provide affordable care to more patient with Hemophilia nA long-term goal to lobby MOH to support affordable treatment products for patients nShort-term goals providing treatment for patients with prioritized needs 现状 n全国血友病协作组成立于1985年，2000年重组 n中国于1990年成为世界血友