Borel-derlon A.,Center Regional Of Traitement Of Lhemophilie |
Gruel Y.,Center Regional Of Traitement Of Lhemophilie |
Navarro R.,Center Regional Of Traitement Of Lhemophilie
Haemophilia | Year: 2013
Summary: Immune tolerance induction (ITI) can eliminate factor VIII (FVIII) inhibitory antibodies that appear during FVIII replacement therapy. If first-line ITI fails, switching to a different FVIII concentrate, especially one containing von Willebrand factor (VWF), has been advocated. The objective of the study was to assess the efficacy and safety of Haemate® P, a plasma-derived FVIII concentrate containing high levels of VWF, as ITI in severe haemophilia A patients who had failed at least one prior ITI attempt with a different FVIII concentrate. In this multicentre, observational study, Haemate® P was administered at a starting dose of 83-308 IU kg-1 day-1 (1500-6000 IU day-1). Efficacy was assessed by standard criteria (e.g. Bethesda titre, FVIII recovery and half-life), and bleeding characteristics. Nine patients from six haemophilia centres were treated with Haemate® P after failing one (n = 2), two (n = 5) or three (n = 2) prior ITI courses. The median time from inhibitor detection to Haemate® P treatment was 5.4 years. The median Haemate® P dose was 134 IU kg-1, and the median treatment duration 32 months. During median of 47 months of follow-up, complete response, partial response and treatment failure were observed in one, three and five patients respectively. Five patients experienced seven adverse events (AEs), including two serious AEs (sepsis). Haemate® P was discontinued due to an AE in one patient with a partial response. Haemate® P salvage ITI resulted in complete or partial tolerization in four of nine patients (44%) who had failed previous ITI attempts using different FVIII concentrates. © 2012 Blackwell Publishing Ltd.
Veyradier A.,Service dHematologie biologique |
Veyradier A.,French Institute of Health and Medical Research |
Veyradier A.,Center National Of Reference Of La Maladie Of Willebrand |
Caron C.,Center National Of Reference Of La Maladie Of Willebrand |
And 13 more authors.
Haemophilia | Year: 2011
Type 2N von Willebrand's disease (VWD) is characterized by a factor VIII (FVIII) deficiency and a low FVIII/VWF ratio related to a markedly decreased affinity of von Willebrand factor (VWF) to FVIII. Type 2N VWD is diagnosed using assays allowing the measurement of plasma VWF capacity to bind FVIII (VWF:FVIIIB). These assays, crucial in order to distinguish type 2N VWD patients from mild haemophiliacs A and haemophilia A carriers, remain exclusively homemade and limited to laboratories possessing a high level of expertise in VWD. We evaluated the first commercial ELISA (Asserachrom® VWF:FVIIIB; Stago) comparated to a reference method in a multicentric study involving 205 subjects: 60 healthy volunteers, 37 haemophiliacs A, 17 haemophilia A carriers, 37 patients with type 2N VWD, 9 heterozygous carriers for a 2N mutation and 45 patients with miscellaneous other types of VWD (all previously characterized). A diluted plasma sample adjusted to 10IUdL -1 of VWF:Ag was incubated with a rabbit antihuman VWF polyclonal antibody. After removing the endogenous FVIII, recombinant FVIII (rFVIII) was added and bound rFVIII was quantified using a peroxydase-conjugated mouse antihuman FVIII monoclonal antibody. The intra-assay and inter-assay reproducibility was satisfactory. In all subgroups, both methods were well correlated. All type 2N VWD patients exhibited a markedly decreased VWF:FVIIIB (lower than 15%) and all heterozygous 2N carriers had a moderately decreased VWF:FVIIIB (between 30% and 65%). All controls (healthy subjects, haemophiliacs A and haemophilia A carriers) had a normal VWF:FVIIIB (higher than 80%) except one healthy volunteer and three haemophiliacs who exhibited a moderately decreased VWF:FVIIIB suggesting a heterozygous status for a 2N mutation. In conclusion, the Asserachrom® VWF:FVIIIB is easy to perform, standardized and accurate for type 2N VWD diagnosis with a 100% sensitivity and specificity. © 2011 Blackwell Publishing Ltd.
Negrier C.,Center Regional Of Traitement Of Lhemophilie |
Seuser A.,Kaiser Karl Klinik |
Forsyth A.,Christiana Care Health System Hemophilia Program |
Lobet S.,Catholic University of Louvain |
And 2 more authors.
Haemophilia | Year: 2013
Most health care professionals involved in the management of people with haemophilia (PWH) believe that exercise is beneficial and its practice is widely encouraged. This article aims to demonstrate that appropriate exercise (adapted to the special needs of the individual PWH) may be beneficial for all PWH through improved physical, psychosocial and medical status. Based on evidence gathered from the literature, many PWH, particularly those using long-term prophylaxis or exhibiting a mild/moderate bleeding phenotype, are as active as their healthy peers. PWH experience the same benefits of exercise as the general population, being physically healthier than if sedentary and enjoying a higher quality of life (QoL) through social inclusion and higher self-esteem. PWH can also gain physically from increased muscle strength, joint health, balance and flexibility achieved through physiotherapy, physical activity, exercise and sport. Conversely, very little data exist on activity levels of PWH in countries with limited resources. However, regarding specific exercise recommendations in PWH, there is a lack of randomized clinical trials, and consequently formal, evidence-based guidelines have not been produced. Based on published evidence from this review of the literature, together with the clinical experience of the authors, a series of recommendations for the safe participation of PWH in regular physical activities, exercises and sport are now proposed. In summary, we believe that appropriately modified programmes can potentially allow all PWH to experience the physical and psychosocial benefits of being physically active which may ultimately lead to an improved QoL. © 2013 John Wiley & Sons Ltd.
Nurden A.T.,Institute Of Rhythmologie Et Of Modelisation Cardiaque |
Pillois X.,Institute Of Rhythmologie Et Of Modelisation Cardiaque |
Pillois X.,French Institute of Health and Medical Research |
Fiore M.,French Institute of Health and Medical Research |
And 23 more authors.
Human Mutation | Year: 2015
We report the largest international study on Glanzmann thrombasthenia (GT), an inherited bleeding disorder where defects of the ITGA2B and ITGB3 genes cause quantitative or qualitative defects of the αIIbβ3 integrin, a key mediator of platelet aggregation. Sequencing of the coding regions and splice sites of both genes in members of 76 affected families identified 78 genetic variants (55 novel) suspected to cause GT. Four large deletions or duplications were found by quantitative real-time PCR. Families with mutations in either gene were indistinguishable in terms of bleeding severity that varied even among siblings. Families were grouped into type I and the rarer type II or variant forms with residual αIIbβ3 expression. Variant forms helped identify genes encoding proteins mediating integrin activation. Splicing defects and stop codons were common for both ITGA2B and ITGB3 and essentially led to a reduced or absent αIIbβ3 expression; included was a heterozygous c.1440-13_c.1440-1del in intron 14 of ITGA2B causing exon skipping in seven unrelated families. Molecular modeling revealed how many missense mutations induced subtle changes in αIIb and β3 domain structure across both subunits, thereby interfering with integrin maturation and/or function. Our study extends knowledge of GT and the pathophysiology of an integrin. © 2015 WILEY PERIODICALS, INC.
Legendre A.-S.,Observatoire du medicament |
Le Monnier S.,Center hospitalier intercommunal Eure Seine |
Chamouni P.,Center Regional Of Traitement Of Lhemophilie |
Damais A.,Pierre Mendès-France University |
And 9 more authors.
Transfusion Clinique et Biologique | Year: 2012
Purpose of the study: The établissement français du sang (EFS) distributes two types of platelet concentrates: using a single donor in aphaeresis platelet concentrate (SDAP), versus pooled platelet concentrates (PPC). A retrospective study performed by the Blood Derivatives Group at Observatory for Drugs, Medical Devices and Therapeutic Innovations (OMEDIT), in collaboration with EFS and haemovigilance correspondents from eight regional health care establishments, has analyzed platelet concentrates prescriptions and the position of the prescribers concerning PPC supply. Material and methods: Between the 2nd and 6th June 2008, 151 platelet concentrates were supplied by ESF. Data were collected for 144 platelet concentrates and in 83 transfused patients with an average age of 50. years. During this study, 33 PPC (23%) and 111 SDAP (77%) were supplied. Results: With regards to the 111 SDAP, the supply of PPC was refused in 47 cases (42%), accepted in 18 cases (16%) and unknown for 46 cases (42%). A total of 51 PPC could be supplied during this period, which represented 35% of platelet concentrates prescriptions. The rate of platelets before transfusion was known for 121 platelet concentrates, the median was 32G·L-1 for SDAP and 44G·L-1 for PPC. Conclusion: More frequent PPC use, with comparable therapeutic efficacy, could be interesting in a context of increasing platelet concentrates consumption in health care establishments. Moreover, prescribers did not seem to be against the idea. An information pamphlet on platelet concentrates was drafted and distributed to prescribers in order to promote the prescription of PPC. A second assessment is planned to measure the impact of this communication. © 2012 Elsevier Masson SAS.
Baur A.,Service de reanimation pediatrique |
Pouyau R.,Service de reanimation pediatrique |
Meunier S.,Center Regional Of Traitement Of Lhemophilie |
Nougier C.,Service dhematologie biologique |
And 6 more authors.
Archives de Pediatrie | Year: 2011
Purpura fulminans (PF) and deep vein thrombosis are rare complications secondary to chicken pox disease. The presence of antibodies reflects an ongoing immunological process and requires specialized management. The present study reports a 4-year-old boy with no medical history who presented with purpura on the legs 10 days after chicken pox eruption. Laboratory tests showed a disseminated intravascular coagulation associated with low plasma protein C and S activities, and the presence of anti-protein S antibodies. A replacement therapy with protein C infusions and fresh frozen plasma was prescribed. The patient also underwent regular sessions of hyperbaric oxygen followed by the surgery. Fourteen days after the beginning of the purpuric lesions, he presented deep vein thrombosis (DVT) of the lower limbs and was treated with unfractionated heparin. This case report illustrates the pathophysiology of DVT occurring in a patient with chicken pox disease (i.e., acquired protein C and S deficiencies and anti-protein S autoantibodies) and emphasizes the utility of thrombophilia testing in order to better adapt treatment. © 2011.
Trossaert M.,Center Regional Of Traitement Of Lhemophilie |
Boisseau P.,Laboratoire Of Genetique Moleculaire |
Quemener A.,University of Nantes |
Sigaud M.,Center Regional Of Traitement Of Lhemophilie |
And 6 more authors.
Journal of Thrombosis and Haemostasis | Year: 2011
Background:In most laboratories, the severity of hemophilia A is assessed by the factor VIII activity (FVIII:C) one-stage assay. However, comparisons of these results with those of two-stage assays can reveal discrepancies and suggest misdiagnosis. Patients/Methods:In this monocentric study, we measured FVIII:C with two methods (one-stage chronometric and chromogenic assays) in 307 (173 families) patients with moderate/mild hemophilia A. To compare results, we used a chronometric/chromogenic ratio. Discrepancy was defined as a ratio <0.5 or >1.5. We studied their putative involvement at known FVIII functional sites, their interspecies conservation status, and their spatial position within the FVIII structure. Results:Thirty-six patients from 17 families exhibited a discrepancy between the two assays: 12 (6.9%) families had a low ratio (<0.5), and five (2.9%) families had a high ratio (>1.5). Qualitative deficiency was diagnosed in about 16% of the families. Molecular studies were performed in 15 of these 17 families, resulting in each case in the identification of missense mutations, including three novel mutations. We were further able to propose a pathophysiologic explanation. Conclusions:In this monocentric study, we have demonstrated a discrepancy between FVIII:C assay results in 10% of families with moderate/mild hemophilia A. The prevalence of 'inverse' discrepancy (i.e. low chronometric/chromogenic ratio) is high as compared with previous reports. We suggest that both FVIII:C assays are recommended in patients with moderate/mild hemophilia A for a complete biological phenotype. This could also improve our knowledge of the FVIII structure-function relationships. © 2011 International Society on Thrombosis and Haemostasis.