Hemophilia severity score system: validation from an Italian Regional Hemophilia Reference Center

We read with interest the recent article by Schulman et al. on a composite score for evaluating the phenotypic severity of hemophilia [1]. The conclusions of the authors regarding the need to validate the score system in countries with different levels of care stimulated us to evaluate it in our context. Thus, we applied the hemophilia severity score (HSS) system to hemophiliacs referred to the Hemophilia Centre of Parma, the reference center for the Region of Emilia-Romagna in Italy [2]. The collection of the patients data required for the calculation of the three parameters of the HSS (bleeding score, joint score, and factor concentrate) was facilitated by the availability, since October 2002, of an electronic database developed to collect clinical data for the Registry and Network of Hemophilia Centres of the Emilia-Romagna Region [3]. In addition, since March 2007, data entry has been improved by the implementation of regional web-based clinical records in which patients can promptly record any bleeds and home treatments [4]. Between October 1998 and September 2008, 65 consecutive patients with hemophilia A or B and basal factor levels between 0 and 0.3 IU/mL were evaluated. According to the original protocol by Schulman et al., additional exclusion criteria were a follow-up less than 10 years for each patient, the presence of an inhibitor at any time before or during the study period, and an age less than 18 years at the end of the observation. Informed consent was obtained from the patients. In addition, only patients with reliable and complete data on bleeding score, joint score and factor concentrate utilization were evaluated in the study. Patients with severe/moderate hemophilia were also tested for two of the more common thrombophilic polymorphisms (factor V Leiden and prothrombin G20210A) [1]. The characteristics of the patients enrolled are summarized in Table 1. When our patients were compared with those reported by Schulman et al., hemophilia A and B ratio, age at mid-term, median age at first bleed and hepatitis C virus infection rate were similar, whereas fewer of our patients were on prophylaxis (45% vs. 79%). Furthermore, the median age of patients who started prophylaxis was higher in our series (15 vs. 8). These latter findings were probably due to the fact that prophylaxis became widely used in Italy only recently, and thus later than in northern countries [5,6]. Finally, although orthopedic joint score and factor consumption per year were lower in our patients with severe hemophilia, statistical significance was reached in the three different groups in both studies (Table 1). The higher number of patients on prophylaxis reported by Schulman et al. explains the higher factor consumption recorded in their study. Table 2 shows the HSS and its components according to Schulman s method. It is of note that we did not perform a separate analysis of hemophilia A and B patients, as the HSS was similar according to disease severity. Although ranges of HSS and of its components were wider in our study, especially for patients with severe hemophilia, maximum values were compatible with those tolerated for each score calculation. In addition, in our study, the HSS of patients with moderate hemophilia was lower than that reported by Schulman et al. This difference was probably due to the fact that four of the five patients with a moderate disease (FVIII:C or FIX:C 0.01– 0.05 IU/mL) had a deficient factor level at the upper limits of the range, and thus a milder clinical phenotype. Figure 1 reports HSS according to factor levels in all patients with severe, moderate and mild hemophilia A or B. Among severe hemophiliacs, the HSS was higher for patients on demand therapy than for those on prophylaxis (P = 0.041), and this reflected statistically significant differences in bleeding and joint Correspondence: Annarita Tagliaferri, Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, Via Gramsci 14, Parma 43100, Italy. Tel. : +390521703971; fax: +390521704332. E-mail: atagliaferri@ao.pr. it