儿童血友病的预防治疗

1血友病儿童的现状血友病是遗传性、伴随终身的出血性疾病。身体各个部位都有可能发生出血,以关节最为常见,肌肉出血次之,内脏出血少见但病情较重。重型血友病儿童多于2岁左右发生关节出血,此后反复的关节出血导致慢性血友病性关节炎进而因关节畸形而致残,几乎是血友病患者的共同结局。     

儿童血友病的预防治疗

1 血友病儿童的现状血友病是遗传性、伴随终身的出血性疾病.身体各个部位都有可能发生出血,以关节最为常见,肌肉出血次之,内脏出血少见但病情较重.重型血友病儿童多于2岁左右发生关节出血,此后反复的关节出血导致慢性血友病性关节炎进而因关节畸形而致残,几乎是血友病患者的共同结局.     

儿童血友病的诊断与治疗

血友病作为一种先天遗传性疾病由于其伴性遗传、外伤后出血和实验室的特殊改变而被人们认识。血友病诊治水平的发展很好地体现了医学、科技发展的历程,其经历了面对死亡的昨天、提高生活质量的今天和期待摆脱疾病束缚的明天。现代儿童血友病治疗理念已经不仅仅是简单的诊断和出血后替代治疗,更强调的是如何减少致残,使患儿获得与其他孩子一样正常生活的机会。综合治疗、家庭治疗和预防治疗的开展是实现血友病患儿正常生活的保障。在我国,由于经济条件的限制,儿童患者的生存状态不容乐观,但是随着国家、社会的逐步重视和医疗事业的发展,儿童血友病患者必将有着更美好的明天。     

血友病的诊断治疗研究进展

血友病是由于基因缺陷而使相关凝血因子含量不足或功能缺陷所致,发病率约５／１０００００－１０／１０００００。血友病分子遗传学的研究进展,高纯化和基因重组凝 因子的使用及对该类病人管理的加强,提高了血友病的基因诊断,治疗水平,降低了输血相关疾病的发生,改善了病人生活质量。     

儿童血友病的治疗

血友病是一种由于FⅧ/FⅨ基因突变所引起的X-连锁隐性遗传性疾病,包括血友病A(由于凝血因子Ⅷ缺陷)和血友病B(由于凝血因子Ⅸ缺陷).根据血浆内凝血因子Ⅷ/Ⅸ浓度,血友病被分为重型(FⅧ/Ⅸ浓度<2%)、中型(FⅧ/Ⅸ浓度2%～5%)、轻型(FⅧ/Ⅸ浓度>5%～40%).     

儿童血友病的治疗

血友病是一种由于FⅧ／FⅨ基因突变所引起的X-连锁隐性遗传性疾病,包括血友病A（由于凝血因子Ⅷ缺陷）和血友病B（由于凝血因子Ⅸ缺陷）。根据血浆内凝血因子Ⅷ／Ⅸ浓度,血友病被分为重型（FⅧ／Ⅸ浓度〈2％）、中型（FⅧ／Ⅸ浓度2％～5％）、轻型（FⅧ／Ⅸ浓度〉5％～40％）。     

中国重型血友病A患儿规律预防治疗的选择及其影响因素分析-来自中国12家血友病中心的调查和分析

目的探讨医疗保险政策及慈善项目对中国重型血友病A患儿选择规律预防治疗的影响。方法 (1)对2007年11月1日至2013年5月31日期间,在中国12个血友病中心接受过Ⅷ因子规律预防治疗的重型血友病A患儿进行回顾性研究。(2)记录研究期间的各项临床资料。(3)从各中心收集重型血友病A患儿选择或放弃规律预防治疗影响因素的调查问卷。(4)查询12个中心(位于11个城市)历年的血友病相关医保政策,比较不同医保报销比例下患儿年均FⅧ使用量及自付水平。比较参加慈善援助项目及未参加慈善援助项目年均FⅧ使用量的差异。结果 (1)2008年开始出现患儿选择规律预防治疗,并且人数呈逐年增加的趋势。(2)患儿选择规律预防治疗的前三位原因为:既往按需治疗效果不理想、当地医保政策改善、患儿或家属对疾病认识提高。中途放弃规律预防治疗的主要原因为家庭经济支付能力不足。(3)研究中83.4%的患儿享受医保报销,其中80.11%患儿的医保政策年度支付上限不低于15万元,可满足其规律低剂量预防方案的医疗费用。(4)医保报销比例高的患儿年均FⅧ使用量相对较高。医保报销比例低的患儿,自付水平明显较高(P0.05)。66.4%的患儿自付水平≥50%,其人均可支配收入的一半以上需用于支付预防治疗费用。(5)预防治疗的患儿中79.6%接受了慈善援助项目的支持。(6)2012年患儿实际年FⅧ使用量均值为30376IU(合999IU/kg),仅为全年坚持规律预防治疗理论用量的62.9%,明显低于高收入国家FⅧ使用量。结论(1)医保政策是影响中国儿童选择和坚持预防治疗的重要因素,慈善援助项目对其起到了推动作用。(2)对于低剂量预防治疗方案来讲,医保报销比例,而非年度支付上限,可能是制约患儿坚持长期规律预防治疗的重要因素。(3)目前中国儿童血友病预防治疗为短疗程、低剂量.与中高收入国家FⅧ使用量存在明显差距,医保政策有待进一步改善。     

儿童血友病家庭治疗专家共识

血友病是一组X染色体连锁的隐性遗传性出血性疾病,临床上主要分为血友病A(凝血因子Ⅷ缺乏症)和血友病B(凝血因子Ⅸ缺乏症)两型.特征表现为出血倾向,临床可表现为关节、肌肉、内脏和深部组织自发性或轻微外伤后出血难止.     

以磁共振评分评估重型血友病A患儿规律低剂量预防治疗的长期关节结局

目的对规律低剂量预防治疗重型血友病A患儿长期随访,采取磁共振等方法评估患儿的长期关节结局,并对影响关节结局的因素进行初步分析。方法 2008年1月—2011年12月就诊于北京协和医院血友病中心,接受规律低剂量FVIII预防治疗的重型血友病A患儿,进行长达10年的长期随访,收集其临床病例资料,统计患儿开始低剂量预防治疗年龄、随访时间、预防时间(总周数)、预防剂量等,应用年关节出血次数(AJBR)、靶关节数、关节磁共振评分(IPSG MRI评分)等评估患儿在长期规律低剂量预防治疗方案下关节的状态及其损伤程度。结果 21例患儿入组年龄为1岁9个月～17岁11个月,随访时间为6～10年,其关节MRI评分为2～24分(13.52±6.17),21/21(100%)有关节损伤,19/21例(91%)患儿有关节软骨损伤,17/21例(81%)患儿有骨质损伤。IPSG MRI评分越高,关节损害越严重;关节MRI评分与年关节出血次数、开始预防年龄有明显相关性(P<0.05)。结论(1)低剂量预防治疗下,长期随访100%患儿仍然有关节受损,说明低剂量方案有待提高;(2)儿童尽早开始低剂量预防性治疗,可有效减少血友病A患儿关节出血次数,可能改善关节结局;(3)关节MRI检查敏感发现关节结构破坏,可能是评估关节早期损伤的首选检查方法。     

Long-term results of central venous access devices in children with haemophilia

Aims  Central venous access devices (CVADs) are often used to provide reliable venous access for factor VIII administration in children with haemophilia. This study investigates their long-term outcome. Methods  A retrospective cohort study of 44 CVADs inserted into 31 children with haemophilia at a single centre between 1991 and 2006. Results  Eight (18%) CVADs are still in place and working well. Fourteen (31.8%) were removed when the child was able to return to peripheral vascular access. Twenty-two (50%) were removed because of complications, most of these children needing a replacement CVAD. The median duration that the first CVAD was in place was 51 months. There were no life-threatening complications. Conclusions  CVADs function well in children with haemophilia for a long time, with a relatively low complication rate, and can tide a child over a difficult period for vascular access.     

Longitudinal growth in HIV-negative boys with haemophilia

It has been shown that HIV-positive haemophilic children develop growth retardation. As not only the HIV infection but also other disease-related factors might compromise growth in these children, growth data were analysed in a longitudinal cross-sectional manner in 84 HIV-negative haemophilic patients from two university clinics. A total of 2–24 height and weight measurements (median 6) were recorded in each patient resulting in 683 single values collected between 1977–1995. Height SDS of all haemophilic boys was −0.31 ± 2.13 (mean ± SD, NS versus 0) and body mass index SDS was 0.21 ± 3.49 (mean SD, NS versus 0) at first measurement and remained unchanged throughout the observation period. Neither height nor body mass index differed with respect to the severity of haemophilia (mild/moderate/severe) or the study centre (Vienna/Prague). Conclusion Growth in HIV-negative patients with haemophilia is not affected in spite of the immunological abnormalities attributed to the substitution therapy or the bleeding episodes in the joints with the potential effect on the growth plate. Received: 5 January 1999 / Accepted: 16 December 1999     

Hepatitis B and C virus infections in Turkish children with haemophilia

We examined 41 Turkish children with haemophilia for evidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections using the enzyme-linked immunosorbent assay (ELISA). Hepatitis B surface antigen was found to be positive in 11 patients (26. 8%) and HCV-specific antibody (anti-HCV) was detected in 10 (24. 4%) patients. There was a close relationship of the number of transfusions of blood plasma to the presence of HCV specific antibody, but not to the serum markers of HBV infection. In countries where HBV infection is commonly seen and problems in transfusion practice continue, as in Turkey, children with haemophilia are at greater risk for HBV and HCV infections.     

Methotrexate infusions as central nervous system prophylaxis in children with acute lymphocytic leukemia: the Norwegian experience

This study included all 690 children in Norway diagnosed as having acute lymphocytic leukemia (ALL) from July 1975 till the end of 1997. Relapses and deaths were monitored until the end of 2000. Neuroleukemia prophylaxis was intravenous methotrexate (MTX) infusions as intermediate-dose methotrexate (IDM) or high-dose methotrexate (HDM) combined with intrathecal MTX. From 1992, systemic therapy was considerably intensified, and, in addition, patients in a subgroup of the high-risk and very high-risk groups were given prophylactic cranial irradiation. The overall findings showed that MTX significantly reduced central nervous system (CNS)-related relapses, and, in general, reinforced systemic therapy reduced significantly non-CNS relapses and deaths. The overall crude survival was 75%. During the study period, the crude survival improved for patients on standard protocols from initially 65 to 90%. Forty patients (6%) developed isolated CNS relapse, 27 (4%) had combined CNS relapse, whereas 180 (26%) had non-CNS relapse. When IDM and HDM were compared, the cumulative risk for isolated CNS relapse was significantly lower with HDM, 12 and 5%, respectively. For any relapses that involved the CNS, the risk remained significantly lower for HDM, 8 versus 18%. Of the 40 patients with isolated CNS relapse, 23 survived (58%).     

重型血友病A患儿关节出血与关节评估的相关性研究

目的了解血友病患儿出血与关节病变之间的关系,为临床治疗和预后判断提供理论依据。方法选取2016年6月至2017年1月于首都医科大学附属北京儿童医院及成都市新世纪妇女儿童医院就诊的1~7岁重型血友病A且有关节出血记录的患儿,以患儿关节出血为研究关节,收集前3个月研究关节的出血次数,应用超声、X线、磁共振成像(MRI)和血友病关节健康评分(HJHS)评分系统对关节进行评估。将关节出血次数与超声、X线、MRI和HJHS评分进行相关性分析,并对超声、X线、MRI和HJHS评分间的相关性进行分析。结果1.共收集重型血友病A患儿18例,年龄(5.6±1.8)岁,共30个出血关节,中位年关节出血次数为4次(4~16次),中位年靶关节出血次数为8次(4~16次)。2.关节出血次数与超声、X线评估有相关性(r=0.390,P=0.033;r=0.517,P=0.008),与HJHS评估、MRI评估均无相关性(均P>0.05)。3.超声、X射线、HJHS和MRI两两之间均呈极显著正相关[r=0.815(超声与X线),r=0.510(超声与HJHS),r=0.812(超声与MRI),r=0.666(X线与HJHS),r=0.911(X线与MRI),r=0.781(HJHS与MRI),均P<0.01]。4.关节超声和/或MRI评估异常的关节中,出血次数与关节评估间均无相关性(P>0.05)。结论关节出血与关节评估获得的关节病变程度结果不一致,因此准确判断关节病变情况需综合评估关节结构、功能等,以便更加全面地指导血友病患儿的治疗。     

Appropriate prophylaxis with restrictive palivizumab regimen in preterm children in Sweden

Aim: Palivizumab (Synagis®) was registered in Sweden in 1999 for prophylaxis against respiratory syncytial virus (RSV) in premature infants. The high costs and the limited knowledge of the efficacy of this substance have led to debate about how and when it should be used. National guidelines for the use of palivizumab in Sweden were constructed in the year 2000. The aim of this study was to evaluate the guidelines. Methods: A nation-wide prospective study was conducted during the two RSV seasons of the years 2000-2002. The paediatric departments in Sweden reported the use of palivizumab, the indication for its use, and the number of infants born preterm before 36 wk of gestation and less than 2 y old who were admitted to hospital for RSV infection. Results: During the two seasons, 218 (3.8%) children who were born before 36 wk of gestation, and 97 (5.4%) who were born before 33 wk, were hospitalized because of RSV infection. Five children were treated with mechanical ventilation. No death caused by RSV was reported. A total of 390 children were treated with palivizumab, and 16 (4.1%) of those who received prophylactic treatment were admitted to hospital with RSV infection.

Conclusion: We consider the comparatively restrictive Swedish recommendations to be safe and recommend that palivizumab should also be used very restrictively in the future. In our opinion, palivizumab in preterm children could be recommended only for those with chronic lung disease younger than 1 y of age, and with active treatment for their disease.     

Treatment of patients with haemophilia and inhibitory antibodies

The development of inhibitory antibodies is a complication which arise in approximately 10% of patients with haemophilia A. The underlying genetic mutation is the single most important predisposing cause, although other risk factors have been identified. Periodic screening for inhibitors is a vital aspect of haemophilia care. The consequences of inhibitor development are very significant in terms of morbidity and cost. Several agents are now available for control of bleeding, but these are often very expensive, the most useful agents include recombinant activated factor VII, prothrombin complex concentrates and porcine factor VIII. It is possible to suppress antibody production with immune tolerance, which is successful in approximately 85% of cases and relapse is rare.     

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目的探讨血友病患儿确诊时间、症状及其关节畸形等情况。方法天津血液学研究所血液病医院于1986年7月至2004年8月,对就诊的429例血友病患儿临床症状出现时间、诊断时间及关节畸形出现的时间进行分析。结果429例血友病患儿,均为男性,血友病A共390例,占90.9%,其中亚临床型5例(1.3%),轻型43例(11.0%),中型181例(46.4%),重型161例(41.3%);血友病B共39例,占9.1%,其中亚临床型2例(5.1%),轻型6例(15.4%),中型26例(66.7%),重型5例(12.8%)。患儿初次出现出血症状的中位年龄为1.6岁(0～12岁);但初次诊断年龄0.3～12.0岁,中位年龄为5.2岁(0.3～12.0岁),两者之间差异具有显著性意义(P<0.01)。结论目前血友病患儿的诊断存在延迟,替代治疗疗程和因子剂量的不足是关节畸形高发生率的原因。     

儿童膜增生性肾小球肾炎的研究进展

膜增生性肾小球肾炎(membranoproliferative glomerulonephritis,MPGN)为免疫病理诊断,其临床表现多样,预后差且病死率高。根据其发病机制的不同,目前最新的分类方法是将 MPGN 分为免疫复合物介导型和补体介导型。根据分类按照可能潜在的病理生理学过程进行相关的病因评估将有助于为MPGN 患者选择更适当的治疗方法。对儿童特发性 MPGN 长期隔日应用糖皮质激素治疗是有益的,生物制剂用于治疗 MPGN 已取得了很大的进展。