儿童血友病综合关怀--儿童血友病的前沿性诊断  

New insights in diagnosis of children hemophilia

作　　者：陈振萍[1] 方拥军[2] 

机构地区：[1]首都医科大学附属北京儿童医院血液肿瘤中心,北京100045 [2]南京医科大学附属儿童医院血液肿瘤科,江苏南京210008

出　　处：《中国实用儿科杂志》2017年第1期23-28,共6页Chinese Journal of Practical Pediatrics

摘　　要：血友病A（hemophilia A）和血友病B（hemophilia B）是X连锁隐性遗传性出血性疾病，遗传特点是男性发病、女性携带。血友病的基因诊断采用方法有DNA常规测序、聚合酶链反应（PCR）法、酶谱分析法、Southern印迹法。目前，临床上开展了FⅧ22内含子倒位分析，可作为重型血友病的筛选试验。产前诊断有助于减少血友病患儿出生率。而凝血因子抑制物的产生是目前造成替代治疗无效的根本原因。危险因素包括：有抑制物家族史、存在高风险基因突变、首次出血发作时强化治疗。不同血友病患者凝血因子的药代动力学（pharmacokinetic，PK）存在明显差异。除了考虑患者出血事件以外，PK参数应该作为预防治疗个体化调整的重要参考指标。相关参数包括半衰期、清除率、体内回收率（IVR）、曲线下面积（AUC）、峰浓度、谷浓度等。不同年龄、体重、血型及von Willebrand因子（vWF）水平等都可能为其影响因素。上述进展有助于针对血友病患者进行个体化治疗策略调整。Hemophilia A（HA） and HB is a X-link recessive hereditary hemorrhagic disorder with genetic characteristics of male suffering and female carrying. In this paper, we will focus on three aspects of hemophilia, including the genetic diagno- sis, inhibitor of factors and pharmacokinetics. The method of gene diagnosis for hemophilia included DNA sequencing, PCR, DGGE, SSCP, etc. At present, the FⅦ intron 22 inversion analysis can be used as a clinical screening test for severe HA. Prenatal diagnosis is helpful to reduce the birth rate of hemophilia. The factor inhibitor causes invalid replacement therapy for hemophilia. Individual hemophilia patients have different pharmacokineties （PK）. In addition to considering the bleeding event, the PK parameters should be considered as an important indicator for adjustment of individual preventive treatment. The relevant PK parameters include the half-life, clearance rate, in vivo recovery rate （IVR）, the area under the curve （AUC）, peak concentration, etc. The influencing factors for PK include age, body weight, blood type and yon Wille- brand factor（vWF） level. The above progress contributes to in- dividual adjustment of treatment strategy for patients with hemophilia.

关 键 词：血友病 基因 抑制物 药代动力学 

分 类 号：R72[医药卫生—儿科]