儿童获得性血友病A2例并文献分析

Clinical characteristics of acquired hemophilia A in childhood (report on two cases and literature review)

目的对儿童获得性血友病A(AHA)的临床特点进行总结,以提高对该病的认识。方法对北京协和医院2002年9月和2008年12月收治的2例儿童AHA及医学引文索引(Medline)检索到的16例患儿,共18例,进行回顾性分析,并与成人获得性血友病的临床特点进行比较。结果儿童AHA发病年龄平均为6.6岁(2～14岁),从出现症状至确诊时间平均3.1个月(1周至2年)。7例(38.9%)可能与感染相关,如上呼吸道感染、咽炎、乳突炎、肺炎等;3例(16.6%)可能与青霉素使用相关;3例(16.6%)可能与肾脏疾病相关,如肾病综合征、Goodpasture综合征等;2例(11.1%)可能与自身免疫性疾病相关,包括系统性红斑狼疮、幼年型类风湿性关节炎;3例(16.6%)无相关基础疾病。临床表现主要为皮肤大片瘀斑(61.1%,11/18)和肌肉或软组织血肿(55.6%,10/18),关节出血相对少见,占11.1%(2/18)。7例(38.9%)患儿经过原发病治疗、替代治疗和(或)免疫抑制治疗,在1～6周内获得缓解(CR),8例(44.4%)在3～60个月获得CR,总CR率达83.3%,2例(11.1%)患儿死亡。活化的部分凝血活酶时间(APTT)、凝血因子Ⅷ活性(FⅧ∶C)及凝血因子Ⅷ抑制物(FⅧ∶Ab)滴度水平与临床出血严重程度以及获得CR的时间均无明确相关性(P>0.05)。结论儿童AHA极罕见,常存在基础疾病,皮肤和软组织出血为其主要临床表现。掌握其临床特点及诊断流程有助于早期诊断、减少误诊。在积极治疗基础疾病的同时,给与替代治疗,必要时加用糖皮质激素或免疫抑制剂,能使本病获得长期CR或治愈。

Objective To review the clinical features, pathogenesis, diagnosis, treatment and prognosis of the reported children with acquired hemophilia A （AHA）, and to enhance the understanding of them. Methods Eighteen children with acquired hemophilia （including 2 cases from our hospital and sixteen cases from MEDLINE search） were retrospectively analyzed and compared with adults with AHA. Results The average age of onset was 6.6 years （ranging from 2 to 14 years）. The average course from initiation of clinical symptom to making definite diagnosis was 3.1 months （ranging from 1 week to 2 years）. The underlying conditions included infection （7 cases, 38.9% ） , penicillin （ 3 cases, 16.6% ） , kidney diseases （ 3 cases, 16.6% ） and autoimmune diseases （ 2 cases, 11.1% ） , and only 3 patients had no reason to detect. The majority presenting symptoms were skin ecchymoses（61.1%, 11/18） and muscle hematoma （55.6%, 10/18）.Seven cases （38.9%） and 8 cases （44.4%） acquired complete remission （CR） by the treatment of underlying conditions and（or no）immunosuppressive agents within 6 weeks and 60 months respectively. The overall CR rate reached 83.3%, only 2 patients died of severe bleeding. The severity of hemorrhage and the time to obtain CR had no correlation with the level of APTT, FⅦ ： C and the titer of FⅧ ： Ab（P〉 0.05）. Conclusion The report of children AHA is rare. It usually has underlying conditions. It is helpful for early diagnosis to understand clinical features and diagnostic flow of children AHA. It has good prognosis by the proper treatment of underlying dieases and necessary immunosuppressive agents.