The thrombin generation (TG) assay evaluates haemostatic balance, which is influenced by the levels of many coagulation factors and inhibitors. Our objective was to identify the determinant factors ...of TG in haemophilia A (HA) and haemophilia B (HB) patients and to compare them to those in healthy controls. Coagulation factor and inhibitor levels, and TG, were measured in platelet‐poor plasma from 40 patients with HA, 32 patients with HB and 40 healthy subjects. Data were analysed using multiple regression models. In HA patients, factor VIII was a positive determinant of endogenous thrombin potential (ETP) and peak, whereas tissue factor pathway inhibitor (TFPI) and factor V were negative determinants of ETP and peak. In HB patients, FIX was a positive determinant of ETP and peak, FVII being a positive determinant of peak. Antithrombin and protein S (PS) were negative determinants of ETP while FX was a negative determinant of peak. Above all, in HB patients, TFPI was a negative determinant of ETP and peak. In healthy subjects, FVIII was a positive determinant of ETP and peak, whereas FX and protein S were negative determinants of these parameters. TFPI was not a negative determinant of either peak or ETP. In haemophilic patients, the determinant factors of TG are all implicated in FXa generation and inhibition, the crucial determinant factor being TFPI whatever the type of haemophilia, A or B. These findings contribute to the rationale that recently place TFPI as a target for innovative therapies of haemophilia.
Background
Data are limited on prostate cancer (PC) management in patients with haemophilia (PWH).
Aim
To describe PC screening and diagnosis, treatment modalities and bleeding complications in a ...group of unselected PWH followed at French Haemophilia Treatment Centres (HTCs)
Patients and methods
PC screening, management and bleeding complications were retrospectively investigated at 14 French HTCs between 2003 and 2018.
Results
Among> 1549 > 50‐year‐old PWHs, 73 (4.7%) underwent PC screening (median age 71.1 years; 67/6 HA/HB, 17/56 severe‐moderate/mild). At diagnosis, haematuria was infrequent. Prophylaxis was administered during 76/86 (88%) prostate biopsies (PB) (n = 67 clotting factor concentrates, CFC; n = 9 desmopressin; n = 17 associated with tranexamic acid, TA). Bleeding (11/86, 12.8%) occurred mainly post‐prophylaxis (median delay: 7 days): haematuria (9/11, 81.8%), and rectal bleeding (2/11, 18.2%) including one major (1.2%). PC was confirmed in 50/86 PB and in two prostatectomy specimens (total n = 50 patients, n = 6 with only active surveillance). Surgery (n = 28/44 patients) was managed with CFC. Fifteen patients had radiotherapy/brachytherapy, 10 had hormone therapy; CFC‐based prophylaxis was only prescribed for brachytherapy (n = 2). Major bleedings occurred in 3/28 (10.7%) and 2/15 (13.3%) patients who underwent surgery and radio/brachytherapy, respectively. No bleeding risk factor was found.
Conclusion
Our data indicate that PB requires prophylaxis for atleast 7 days, using CFC, desmopressin or TA in function of haemophilia severity. PC surgery should be considered at high bleeding risk. Long‐term post‐procedural CFC or oral TA could be discussed. Radiotherapy/brachytherapy also should be managed with prophylaxis (CFC or TA).
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.
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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.
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