Total knee arthroplasty in hemophilic arthropathy.

UNLABELLED: 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.

Two novel mutations, Q1053H and C1060R, located in the D3 domain of von Willebrand factor, are responsible for decreased FVIII-binding capacity.

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.

Prevalence of IgG antibodies to human parvovirus B19 in haemophilia children treated with recombinant factor (F)VIII only or with at least one plasma-derived FVIII or FIX concentrate: results from the French haemophilia cohort.

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.