Validation of a composite score for clinical severity of hemophilia

INTRODUCTION: Evaluation of modulators of the phenotypic expression of hemophilia may benefit from a scoring system that reflects several aspects of the clinical severity instead of only one dimension. METHODS: We describe here how we constructed a composite Hemophilia Severity Score (HSS) and performed validation. The items in the HSS are annual incidence of joint bleeds, World Federation of Hemophilia Orthopedic joint score, and annual factor consumption. The latter two were adjusted for age at start of prophylaxis and body weight. Data for 100 adolescent or adult patients with hemophilia A or B in the mild, moderate or severe form without inhibitors were collected for the 1990-1999 period. We evaluated the reliability (multidimension property, test-retest) and validity (content, convergent, discriminant and known groups) of the score. RESULTS: The HSS ranged from 0 to 0.94 and was higher in severe hemophilia A than severe hemophilia B (median 0.50 and 0.24; P = 0.031). The validation indicated that the HSS is reliable and reflective of the clinical severity of hemophilia. The presence of factor V G1691A or prothrombin G20210A polymorphisms was found in 13 patients. The clinical severity, measured as the HSS or each of the three components, appeared to be modified by prothrombin G20210A but not by FV G1691A. CONCLUSION: The HSS is a well-defined tool that provides a comprehensive representation of the clinical severity of hemophilia in adults. It would be useful in larger studies on the assessment of modulators of the phenotypic expression of hemophilia.