To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline ...compliance.
This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation).
We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with “timely long-term prophylaxis” as compared with “delayed long-term prophylaxis”: hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with “long-term prophylaxis guideline compliance” vs “long-term prophylaxis anticipation.”
This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.
Fifteen previously untreated patients (Pups) with severe haemophilia B (factor IX activity < or = 2 U/dl) only treated with one brand of plasma-derived high purity factor IX concentrate (FIX LFB) ...were studied. Age at first injection varied from 1 to 137 months and follow-up since this first injection from 21 to 86 months (median: 35). Cumulative exposure days (CED) were from 4 to over 100 (median: 26). Among these 15 Pups only one developed an inhibitor. Mutation analysis performed in all patients showed total gene deletion in the patient with inhibitor, partial gene deletion in another one, and missense mutations in 9 families. Mutation was not found in one patient. Actually, according to the data already published, only two patients were at high risk for inhibitor development in our population. Our study, although rather small, confirms the previously reported low incidence of inhibitors in haemophilia B. Large studies on incidence of FIX inhibitors are indeed difficult to perform, due to both the overall small number of severe haemophilia B patients and the low incidence of FIX inhibitors. Consequently, the impact of bias, such as prevalence of different types of gene defects in a given population, is major. Therefore, any study, dealing with incidence of FIX inhibitors in severe haemophilia B should report, for each patient, the type of gene defect.
In this study, we reinvestigated a 20‐year‐old woman, the first cousin of two brothers with severe haemophilia A. This patient was previously assumed to be a carrier of haemophilia A due to her FVIII ...deficiency. We identified a novel FVIII gene mutation in the family and demonstrated that the FVIII deficiency in this female patient did not result from this gene mutation, but was linked to molecular defects in the von Willebrand factor gene.
In type 2N von Willebrand disease (VWD), von Willebrand factor (VWF) is characterized by a markedly decreased affinity for Factor VIII (FVIII), and the mutations responsible are essentially located ...in the D′ domain of VWF. We report the identification, in seven unrelated French families, of two novel type 2N VWD mutations, Q1053H and C1060R (Gln290His and Cys297Arg in mature VWF sequence), in exon 24 of the VWF gene. These missense mutations have been identified in the heterozygous, homozygous or hemizygous states. Using site‐directed mutagenesis and transient expression in COS‐7 cells, we showed that both mutations, although located in the D3 domain of VWF, outside the tryptic fragment containing the FVIII domain, dramatically decrease the binding of VWF to FVIII. In contrast, the R924Q substitution, which was identified in a patient who was heterozygous for C1060R, was shown to be a polymorphism.
Total knee arthroplasty in hemophilic arthropathy Legroux-Gérot, Isabelle; Strouk, Guillaume; Parquet, Armelle ...
Joint, bone, spine : revue du rhumatisme,
02/2003, Letnik:
70, Številka:
1
Journal Article
Recenzirano
Chronic arthropathy causes major functional disability in patients with severe hemophilia.
Objective. –
To evaluate the results of total knee arthroplasty (TKA) and its impact on both quality of life ...and clotting factor use in patients with severe hemophilia.
Patients and methods. –
We evaluated 17 TKAs in 12 patients. The TKAs were performed between 1986 and 1996, and follow-up was 8–132 months (mean, 54 months). Mean age at arthroplasty was 39 years (22–51 years). Quality of life was evaluated using the Short Form 36 (SF-36).
Results. –
Results were good or excellent in 94% of patients. The improvement was greatest for pain. Recurrent hemarthrosis in six patients and development of an anticoagulant in two patients were the only postoperative complications. Clotting factor use did not decrease significantly after surgery. SF-36 scores showed an increase in physical activity responsible for an improvement in quality-of-life indicators. However, this improvement in functional capabilities seemed to wane over time as a result of arthropathy in other joints and of intercurrent diseases.
Conclusion. –
TKA for hemophilic arthropathy provides good results that translate into quality-of-life gains.
Human parvovirus B19 (B19) has been transmitted by some brands of virally attenuated plasma‐derived factor VIII (FVIII) or IX (FIX) concentrates. To quantify the differences of human parvovirus B19 ...risk transmission between albumin‐stabilized recombinant factor and plasma‐derived factor, we studied the prevalence of IgG antibodies to B19 (anti‐B19) in 193 haemophiliac children between 1 and 6‐years of age who had previously been treated with albumin‐stabilized recombinant FVIII only (n = 104), and in children previously treated with solvent/detergent high‐purity non‐immunopurified and non‐nanofiltered FVIII or IX concentrates (n = 89). Association between the prevalence of anti‐B19 and the treatment group was analysed using multivariate logistic regression. Age, severity and type of haemophilia, number of cumulative days of exposure to factor VIII or IX, previous history of red blood cells or plasma transfusion were considered as potential confounding variables. A higher prevalence of anti‐B19 was found in children previously treated with solvent/detergent high‐purity non‐immunopurified and non‐nanofiltered FVIII or IX concentrates than in children treated with albumin‐ stabilized recombinant FVIII only (OR: 22·3; CI: 7·9–62·8), independently of the other factors studied.
A factor VIII (FVIII) concentrate, virus-inactivated by the solvent/detergent procedure, was studied in vitro. In contrast with most high-purity, virus-inactivated FVIII concentrates, it contains not ...only high levels of von Willebrand factor (vWF) antigen and ristocetin cofactor activity but also high molecular weight forms of von Willebrand factor. Furthermore, it is able to promote platelet adhesion on collagen in a perfusion system. In vivo studies performed in patients with different types of von Willebrand's disease provided evidence that this concentrate corrects Duke's bleeding time and prevents or stops haemorrhages. Thus, the particular advantages of this FVIII/vWF preparation are safety, low content of contamination proteins, and efficacy in von Willebrand's disease.
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