血友病A患者凝血因子Ⅷ抑制物筛查及分析

摘要

本研究通过检测重型血友病A(hemophilia A,HA)患者凝血因子Ⅷ(FⅧ)抑制物,探讨抑制物阳性患者基因突变情况.选取58例一期法检测FⅧ:C均小于1% HA患者,以APTT法为基础进行FⅧ抑制物筛查,筛查阳性者用Bethesda法进行FⅧ抑制物定量分析.以基因组DNA为模版,对抑制物阳性患者FⅧ12、14、16外显子进行基因扩增,PCR产物通过直接测序检测突变情况.结果表明:58例HA患者中4例(6.9%)抑制物检测为阳性,FⅧ12、14、16外显子基因均未发现基因突变.结论:本组病例HA患者抑制物阳性率低于国外文献报道,抑制物产生的原因有待于进一步研究.%In order to detect coagulation factor Ⅷ ( FⅧ ) inhibitor in patients with severe hemophilia A (HA) and preliminarily study the genetic mutation in patients with inhibitor positive.Totally 58 patients with HA ( FⅧ: C ＜ 1％ )were enrolled.FⅧ: C activity was measured by one-stage coagulation assay.FⅧ inhibitor was screened by using APTT method and FⅧ inhibitor in screened positive patients with HA was quantitively analyzed by using Bethesda method.Using genomic DNA as template, 12, 14, 16 exons of FⅧ in screened positive patients were amplified, and the mutations of amplified products were detected by direct sequencing.The results indicated that the FⅧ inhibitor could be detected in 4 patients (6.9％) from 58 HA patients, no gene mutations in 12, 14, 16 exons of FⅧ were found.It is concluded that the positive rate of FⅧ inhibitor in HA patients is lower than that reported in literature.The causes of inhibitor production needs to further investigate.