ALBERT

Description: Introduction Most of the current discussion about prophylaxis for severe hemophilia patients is on the dose and when to start. However, as hemophilia is a chronic disease, it is important to evaluate the duration of prophylaxis. The aim of this study was to study and compare adherence to prophylaxis and outcome of severe hemophilia patients. Methods All patients with severe hemophilia A and B (factor VIII/IX

Description: Introduction The aim of this study was to describe variability in bleeding pattern in a single center cohort of severe hemophilia patients treated with prophylaxis. Methods At the Van Creveldkliniek, all patients with severe hemophilia born between 1944 and 2002 were followed from 1972 onwards. Data on bleeding characteristics and treatment were collected yearly and Pettersson scores were performed with five-year intervals. Prophylactic dose was adjusted always according to bleeding pattern. Since the number of accepted bleeds has decreased over the years, each treatment dependent indicator was described stratified for age. Age specific quartiles for the different indicators were used as arbitrary cut-off values. Results Data on prophylaxis were available for 247 patients, and a total of 2760 follow up years on prophylaxis were collected. Variability in treatment characteristics is shown in Table 1. Treatment characteristics and clinical manifestations per age group Year of birth 1985–2002 1968–1985 1944–1968 Values are means (interquartile range) n 66 87 94 Follow-up per patient (yr) 6.6 18.0 22.6 Age at first joint bleed (yr) 1.8 (0.7–3.7) - Annual clotting factor use (IU/kg/yr) 2790 (2282–3321) 1989 (1654–2350) 1458 (1119–1790) Joint bleeds per year 2.6 (1.0–3.7) 2.9 (1.3–5.1) 4.5 (2.2–9.9) Pettersson score (max 78 points) 0.0 (0.0–2.5) 15.1 (6.0–22.0) 44.8 (35.5–56.2) The variation in annual clotting factor use was used as a marker of bleeding pattern. Age at first joint bleed was inversely related to annual clotting factor use in the youngest age group. Using cut off levels of the 25th and 75th percentiles (P25 and P75) of age at first joint bleed and annual clotting factor use, 10% of patients were identified as patients with a milder bleeding pattern (i.e. age at first joint bleed above P75 and annual clotting factor use below P25) and 9.3% as patients with a more severe bleeding pattern. Using annual clotting factor use and joint bleed frequency in the middle group, 8.0% of patients were identified as patients with a milder phenotype and 10.3% as patients with a more severe bleeding pattern. In the oldest group, Pettersson scores were positively associated with annual clotting factor use. Using these parameters, 14% of the patients were identified as patients with a milder bleeding pattern. Due to the ceiling effect of the Pettersson score, these parameters could not be used to identify patients with a more severe bleeding pattern. Conclusion There is considerable variation in bleeding pattern of patients with severe hemophilia. Combinations of bleeding and treatment characteristics could be used as indicators of phenotype identifying 8 to 14% patients with a milder bleeding pattern and 9 to 10% of patients with a more severe bleeding pattern.

Description: Introduction Patients with severe hemophilia A have considerably different factor VIII half-lives. Whether this is associated with clinical characteristics has not been reported. The aim of this study was to describe the effect of half-life on the clinical characteristics of patients with severe hemophilia. Patients and Methods Patients were selected from a single-centre cohort of 214 patients with severe hemophilia, born between 1944 and 1995. To improve efficiency we measured factor VIII half-life in the patients with the most severe and the mildest clinical phenotypes of severe hemophilia. Patients were selected according to age at first joint bleed, annual joint bleed frequency, clotting factor consumption and radiological Pettersson scores. A first blood sample was taken after a period of 72 hours in which the patient did not use factor VIII. After infusion with 50 IU factor VIII/kg, blood was collected at 15, 30 minutes and 1, 3, 5, 24, 30, 48 and 60 hours. From 1972 onwards, data on joint bleed frequency, clotting factor use and age at first joint bleed were collected from the patients’ files. Pettersson scores were performed at five-year intervals. For calculations of annual clotting factor use (IU/kg/yr) and number of joint bleeds per year, the last 5 years of follow-up were used. Linear regression analysis was used to assess the relation between clinical characteristics and factor VIII half-life. Results Factor VIII half-life was measured in 42 patients and ranged from 7.4–20.4 hours, with a median of 11.8 hours. One hour increase in factor VIII half life was associated with a decrease of 96 (SD 45) IU clotting factor use per kg per year (p