Pernod G, Vinciguerra C, Gaucher C, Mazurier C, Polack B, Négrier C
Laboratoire d'Hématologie, CHU de Grenoble, France.
Thromb Haemost. 1996 Aug;76(2):151-5.
Multiple coagulation disorders are unusual. We report here a combination of haemophilia B Leyden with type 1 von Willebrand disease (vWD) affecting different members of the same family. Haemophilia B Leyden was due to a -6 G-->A mutation within the promoter of the factor IX gene and was responsible for a mild haemophilia in the father of the proband. The proband and her sister (age 4 and 6) exhibited a twofold lower level of factor IX activity (0.4 IU/ml) than the paternal grandmother (0.95 IU/ml). The differences in F IX levels in the three carriers of the same -6 G-->A mutation suggest the implication of an age-related mechanism responsible for the increase in factor IX plasma level. Haemophilia B Leyden patient and carriers suffered also from a mild von Willebrand disease. The diagnosis of this associated type 1 vWD was performed by assaying plasma von Willebrand factor together with multimer electrophoretic studies and DDAVP test. The inheritance of this vWD was investigated by haplotype analysis of the vWF gene. Individuals affected by such an association are actually asymptomatic, but per- and post-operative bleeding risk remains to be evaluated.
多种凝血障碍较为罕见。我们在此报告1例莱顿B型血友病与1型血管性血友病（vWD）合并存在于同一家族不同成员中的病例。莱顿B型血友病是由凝血因子IX基因启动子内的-6 G→A突变引起的，该突变导致先证者的父亲患有轻度血友病。先证者及其妹妹（分别为4岁和6岁）的凝血因子IX活性水平（0.4 IU/ml）比其祖母（0.95 IU/ml）低两倍。同一-6 G→A突变的三位携带者中凝血因子IX水平的差异表明存在一种与年龄相关的机制，该机制导致血浆中凝血因子IX水平升高。莱顿B型血友病患者及其携带者还患有轻度血管性血友病。通过检测血浆血管性血友病因子、进行多聚体电泳研究及去氨加压素试验对这种合并存在的1型vWD进行诊断。通过对vWF基因进行单倍型分析来研究这种vWD的遗传情况。受这种合并症影响的个体实际上并无症状，但围手术期及术后出血风险仍有待评估。
