Plug Iris, Mauser-Bunschoten Eveline P, Bröcker-Vriends Annette H J T, van Amstel Hans Kristian Ploos, van der Bom Johanna G, van Diemen-Homan Joanna E M, Willemse José, Rosendaal Frits R
Leinden Unversity Medical Center, Clinical Epidemiology, Leiden, Netherlands.
Blood. 2006 Jul 1;108(1):52-6. doi: 10.1182/blood-2005-09-3879. Epub 2006 Mar 21.
A wide range of factor VIII and IX levels is observed in heterozygous carriers of hemophilia as well as in noncarriers. In female carriers, extreme lyonization may lead to low clotting factor levels. We studied the effect of heterozygous hemophilia carriership on the occurrence of bleeding symptoms. A postal survey was performed among most of the women who were tested for carriership of hemophilia in the Netherlands before 2001. The questionnaire included items on personal characteristics, characteristics of hemophilia in the affected family members, and carrier testing and history of bleeding problems such as bleeding after tooth extraction, bleeding after tonsillectomy, and other operations. Information on clotting factor levels was obtained from the hospital charts. Logistic regression was used to assess the relation of carrier status and clotting factor levels with the occurrence of hemorrhagic events. In 2004, 766 questionnaires were sent, and 546 women responded (80%). Of these, 274 were carriers of hemophilia A or B. The median clotting factor level of carriers was 0.60 IU/mL (range, 0.05-2.19 IU/mL) compared with 1.02 IU/mL (range, 0.45-3.28 IU/mL) in noncarriers. Clotting factor levels from 0.60 to 0.05 IU/mL were increasingly associated with prolonged bleeding from small wounds and prolonged bleeding after tooth extraction, tonsillectomy, and operations. Carriers of hemophilia bleed more than other women, especially after medical interventions. Our findings suggest that not only clotting factor levels at the extreme of the distribution, resembling mild hemophilia, but also mildly reduced clotting factor levels between 0.41 and 0.60 IU/mL are associated with bleeding.
在血友病杂合子携带者以及非携带者中观察到多种凝血因子VIII和IX水平。在女性携带者中，极端的莱昂化可能导致凝血因子水平降低。我们研究了杂合性血友病携带者状态对出血症状发生的影响。对2001年前在荷兰接受血友病携带者检测的大多数女性进行了邮政调查。问卷包括个人特征、受影响家庭成员的血友病特征、携带者检测以及拔牙后出血、扁桃体切除术后出血和其他手术等出血问题的病史。从医院病历中获取凝血因子水平信息。使用逻辑回归评估携带者状态和凝血因子水平与出血事件发生之间的关系。2004年，发放了766份问卷，546名女性回复（80%）。其中，274名是A型或B型血友病携带者。携带者的凝血因子水平中位数为0.60 IU/mL（范围为0.05 - 2.19 IU/mL），而非携带者为1.02 IU/mL（范围为0.45 - 3.28 IU/mL）。凝血因子水平在0.60至0.05 IU/mL之间与小伤口出血时间延长以及拔牙、扁桃体切除术后和手术后出血时间延长的相关性越来越高。血友病携带者比其他女性更容易出血，尤其是在医疗干预后。我们的研究结果表明，不仅分布极端处类似于轻度血友病的凝血因子水平，而且凝血因子水平在0.41至0.60 IU/mL之间轻度降低也与出血有关。
