Who Are the Type 2 Von Willebrand Disease Patients? Results from Interim Analysis of the French HRQoL Study: Wish-Qol.

Abstract Type 2 von Willebrand disease (VWD) includes a wide range of qualitative abnormalities of von Willebrand factor (VWF) function and structure resulting in various bleeding phenotypes. Variants 2A, 2B and 2M are mainly related to abnormal interaction of VWF with platelets and/or the subendothelium. Mucocutaneous bleeds such as epistaxis, menorrhagia and gastro-intestinal bleedings are the most frequently reported in these subtypes, while in patients with type 2N VWD characterized by a defective binding of VWF to FVIII, a phenotype with symptoms suggestive of mild/moderate hemophilia A is common. Are type 2 VWD female patients' bleeding score, clinical phenotype and impairment of Quality of Life (QoL) more severe than the males' ones? To answer this question, we report here results of VWD type 2 patients enrolled in the French Heath related Quality of Life study: WiSH-QoL. This study is conducted with the French Reference Centre for von Willebrand Disease (CRMW). Clinical phenotype such as bleeding score (Tosetto score), biological profile and genotype are documented. Clinical characteristics and therapeutic approach are also recorded. Patients are treated with WILFACTIN®, triple-secured plasma-derived VWF with a low factor VIII content. Information on socio-demographic and resources consumption are gathered by patients in their diary. HRQoL is assessed with the generic SF-36 (for adults), the chronic-generic DISABKIDS Short Form (for children and adolescents), the VWD-specific HRQoL questionnaire VWD-QoL (for adults, children, adolescents and parents with a proxy version), the VWD-specific treatment satisfaction assessment VWD-Sat (for adults and parents with a proxy version). The Impact on Family (IOF) Scale is dedicated to caregivers of children with VWD. At least 350 patients will be followed during 2 years. During the recruitment period (Oct. 2014 - Nov. 2017), 357 patients were enrolled. At the time of this analysis, data at inclusion on 355 patients were evaluable. Focus was made on the 226 type 2 VWD patients: 141 (62.4%) females and 85 (37.6%) males, median age and range at study entry 32.7 (1-78) and 26.4 (1-83) years, respectively. The majority of them were adults with 101 (71.6%) females and 49 (57.6%) males. 76 patients were below 18 years (40 (28.4%) females and 36 (42.4%) males). In the female subgroup, 81 were women of child-bearing age (15-50 y.o), 27 under 15 years with 21 prepubertal children and 33 above 50 years. The median age at diagnosis was 11.5 years (range 0-78) associated with a family history of VWD in the majority of patients (178, 78.8%), earlier in males' life (6 y) than in females (15 y). The first substitutive treatment by VWF was administered at a median age of 19.0 years (range 0-78), with 13.0 years for males compared to 23.5 y for females. At baseline, 23 (10.2%) patients (12 females and 11 males) had reported GI manifestations. The patients were 64 patients with type 2A, 52 with type 2B, 68 with type 2M, 12 with type 2N and 30 with type 2 unspecified. The median Tosetto bleeding score (BS) reported for 202 patients was +7.0 (range -1 to 25), higher +8.0 (range -1 to 25) in female compared to +5.0 (range 0 to 21) in male patients. It was also able to distinguish disease severity by variants as shown in table1. Whatever the variants (2A, 2B, 2M and 2N VWD,) the women of child-bearing age group had the highest BS. At enrollment, 62 female patients (44.0%) have already received a concomitant treatment with Iron, oral contraceptive, intra-uterine device. In the group of 64 women who had experienced a total of 136 deliveries (mainly vaginal deliveries (107, 78.7%) and C. Section (29, 21.3%)), the mean number of childbirth was 2.1 (range 1-5). Post-Partum Hemorrhages occured in 42 of these cases (31.3%), mainly within 48 hours after giving birth in 27 cases (67.5%) out of the 40 cases with available data. Were also found differences in both Physical and Mental Component Score of the generic SF-36 with higher impairments in HRQoL in adults females than in males (PCS 54.04 vs 55.22) MCS (44.71 vs. 47.85). The same tendency was seen with the Normalized Global score VWD-Specific in adults with higher score in females than in males (17.26 vs 13.91). This study with HRQoL results will bring a deeper insight into type 2 VWD patients' real daily life. These findings may teach us what would be the best care for VWD patients and especially for females who need definitely specific health care throughout their fertile life. Disclosures Borel-Derlon: Octapharma: Other: Clinical Research Investigator; LFB: Membership on an entity's Board of Directors or advisory committees; Shire: Other: Principal investigator; Novonordisk: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees. Desprez:LFB: Other: Investigator. Volot:LFB: Other: Investigator. Pan-Petesch:LFB: Other: Investigator. Chatelanaz:LFB: Employment. Doriat-Robin:LFB: Employment. Veyradier:LFB: Other: Investigator. Von Mackensen:LFB: Membership on an entity's Board of Directors or advisory committees.