Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations.

BACKGROUND: Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA and pose a potential for misdiagnosis. OBJECTIVES: To investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities and VWF genotypes. PATIENTS/METHODS: Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, a patient's VWF capacity to bind FVIII (VWF:FVIIIB) and VWF sequence. RESULTS: Four cases had VWF:Ag < 3 IU dL(-1) and VWF mutations consistent with Type 3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type 1 VWD (VWD1) (n = five cases and one control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n = 1 case). One control had VWF:Ag < 30 IU dL(-1) and seven patients (four cases and three controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB. CONCLUSIONS: These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy.

Comparison of eating disorders and body image disturbances between Eastern and Western countries.

Factors associated with the development of eating disorders in countries with non-Western cultures have not been adequately investigated in relation to Westernized countries. We therefore studied 243 girls [age =16.5+/-1.2 (SD)], recruited from schools in India, Tibet, the US and France. They completed the Figure Rating Scale (FRS), the Eating Attitudes Test (EAT), and the Beck Depression Inventory (BDI). The Tibetan group had a lower body mass index (BMI) than the other groups (p<0.0001), which did not differ from each other. All groups differed significantly on socio-economic status (SES), with those living in India having the highest (p<0.0001). Prior to controlling for age, SES, and BMI, there were no significant differences on any psychological measure between the individual countries, or when collapsed by East vs. West. However, after controlling for the same covariates, the Tibetan group selected a significantly larger current (p<0.0001) and ideal body size (p=0.03), compared to all the other countries, and had more body image discrepancy than the American group (p=0.04). After controlling only for BMI, the girls from the East had a larger current and ideal, but no difference on body image discrepancy. Body image discrepancy scores were best predicted by EAT scores and BMI, accounting for 35% of the variance (p<0.0001). EAT scores themselves were best predicted by mother's education, BDI, body image discrepancy, and drug and tobacco use, accounting for 33% of the variance (p<0.0001). Unlike some other studies, we did not observe greater body image discrepancy and eating pathology in Western cultures, whether or not controlling for age, SES, and BMI. There were no differences in eating and depression pathology between those in the US, France, or India. Indeed, the Tibetans, after controlling for their low BMI and SES, had the greatest body image discrepancy.