The substantial impact of von Willebrand disease on menstruation.

von Willebrand disease (vWd) is the most common of all congenital bleeding disorders with an estimated prevalence of 1-3% in the general population. However, the gynecological complications have not been thoroughly described.Objective: To compare the clinical and quality of life aspects of vWd in menstruating women in relation to a cohort of menstruating women in the general population.Methods: A patient questionnaire and provider survey of the medical and quality of life aspects of menstruation was administered to 81 menstruating vWd patients registered at four geographically linked Hemophilia Treatment Centers. The questionnaire was also administered to 150 menstruating women volunteers that comprised a control group used to determine normal coagulation levels in menstruating women. We assessed the impact on quality of life of menses in both of the cohorts by a Likert scale of 1-10 with 10 being "most significant impact" using 7 quality of life parameters with those comparisons by Wilcoxon rank sum test.Results: 88% of the vWd patients (pts) had type I vWd, the remaining Type II or unknown. The mean age of the vWd patients was 31.6 +/- 10.3; the mean age of the control group was 35.5 +/- 7.6. The following comparisons were made using chi(2) and Wilcoxon rank sum test:Conclusions: vWd markedly diminishes the quality of life during menses. This observation warrants efforts to reduce the attendant morbidities of vWd in menstruating women.

Moderate hemophilia B Leyden: identification by polymerase chain reaction, sequencing, and oligomer restriction.

Hemophilia B Leyden is a rare form of congenital factor IX deficiency which is characterized by severe factor IX deficiency at birth, which ameliorates after puberty. It is caused by mutations in the factor IX gene promoter region and the postpubertal amelioration is thought to be mediated by the action of testosterone on an androgen response element located in the promoter region. Three kindreds have been previously reported with a milder form of hemophilia B Leyden, associated with a guanine to adenine transition at nucleotide position -6 of the promoter region. We now report a fourth kindred with this mutation. The proband was a newborn with a factor IX level of 2.5%, his 12-year-old half-brother had a level of 28%, and his mother's 56-year-old maternal cousin had a level of 60%. A G to A transition at nucleotide -6 of the promoter region was demonstrated by cloning and sequencing polymerase chain reaction products from the half brother, and the mother was demonstrated to be a carrier. The mutation eliminates a TaqI restriction endonuclease site normally present in the wild type promoter, and the mother's cousin was demonstrated to carry the mutation by the absence of digestion with TaqI. The identification of hemophilia B Leyden with this specific mutation has practical importance to the clinical management because of its unique natural history and significantly better prognosis than classical hemophilia B.