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- Borel-Derlon, A., et al.
(författare)
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Treatment of severe von Willebrand disease with a high-purity von Willebrand factor concentrate (Wilfactin (R)): a prospective study of 50 patients
- 2007
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 5:6, s. 1115-1124
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: A plasma-derived von Willebrand factor (VWF) concentrate with low factor VIII (FVIII) content was specifically developed to treat von Willebrand disease (VWD). Efficacy and safety were investigated by merging the results of two comparable protocols conducted prospectively in 5 European and 12 French centers. Methods and results: Fifty patients with clinically severe VWD (72% had VWF ristocetin cofactor activity less than 10 IU dL(-1) and 46% had FVIII < 20 IU dL(-1)) were treated with the concentrate as the only therapy, except for clinical situations requiring a priming dose of FVIII to rapidly correct an intrinsic coagulation defect. A total of 139 spontaneous bleeding episodes were treated; only 53 (38%) needed a concomitant FVIII dose. Outcome was excellent or good in 89% of the episodes. Forty-four patients underwent 108 surgical or invasive procedures. Outcome was excellent or good in 95 scheduled procedures (only VWF was infused) and 13 emergency procedures (a priming FVIII dose was co-administered with the first VWF infusion). There were no thrombotic complications and none of the 18 patients with type 3 VWD developed anti-VWF or anti-FVIII antibodies. Conclusions. This concentrate safely and effectively provides hemostasis in patients with clinically severe VWD.
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- Collins, P. W., et al.
(författare)
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Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A
- 2009
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 7:3, s. 413-420
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level <1 IU dL(-1). Studies to date, however, have not demonstrated a strong link between FVIII level and the bleeding rate. OBJECTIVES: To assess the effect of FVIII level on break-through bleeding in patients with severe hemophilia A on prophylaxis. PATIENTS/METHODS: This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII <1 IU dL(-1)) who were treated with prophylactic FVIII as part of clinical studies assessing pharmacokinetics, safety and efficacy of a recombinant FVIII (Advate). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). RESULTS: The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. Conclusions: These data have important implications for the management of patients with severe hemophilia.
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- Eikenboom, J, et al.
(författare)
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Linkage analysis in families diagnosed with type 1 von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 VWD
- 2006
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:4, s. 774-782
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Tidskriftsartikel (refereegranskat)abstract
- Background: von Willebrand disease (VWD) type 1 is a congenital bleeding disorder caused by genetic defects in the von Willebrand factor (VWF) gene and characterized by a reduction of structurally normal VWF. The diagnosis of type 1 VWD is difficult because of clinical and laboratory variability. Furthermore, inconsistency of linkage between type 1 VWD and the VWF locus has been reported. Objectives: To estimate the proportion of type 1 VWD that is linked to the VWF gene. Patients and methods: Type 1 VWD families and healthy control individuals were recruited. An extensive questionnaire on bleeding symptoms was completed and phenotypic tests were performed. Linkage between VWF gene haplotypes and the diagnosis of type 1 VWD, the plasma levels of VWF and the severity of bleeding symptoms was analyzed. Results: Segregation analysis in 143 families diagnosed with type 1 VWD fitted a model of autosomal dominant inheritance. Linkage analysis under heterogeneity resulted in a summed lod score of 23.2 with an estimated proportion of linkage of 0.70. After exclusion of families with abnormal multimer patterns the linkage proportion was 0.46. LOD scores and linkage proportions were higher in families with more severe phenotypes and with phenotypes suggestive of qualitative VWF defects. About 40% of the total variation of VWF antigen could be attributed to the VWF gene. Conclusions: We conclude that the diagnosis of type 1 VWD is linked to the VWF gene in about 70% of families, however after exclusion of qualitative defects this is about 50%.
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- Eliasson, Åsa, et al.
(författare)
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Incidence and risk of venous thromboembolism in patients with verified arterial thrombosis : a population study based on 23,796 consecutive autopsies
- 2006
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:9, s. 1897-1902
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between atherothrombotic disease and venous thromboembolism (VTE) remains unclear. Patients and methods: In a cohort of 23 796 consecutive autopsies, performed using a standardized procedure and representing 84% of all in-hospital deaths between 1970 and 1982 in an urban Swedish population, we investigated the relationship between verified arterial thrombosis and VTE, with the hypothesis that patients with thrombosis in major artery segments have increased odds of VTE. Results: We found an increased risk of VTE in patients with arterial thrombosis (Odds ratio; OR adjusted for gender and age 1.4, 95% confidence interval; CI 1.3-1.5) (P < 0.001). Patients with cervico-cranial and peripheral artery thrombosis had an excess risk even when controlling for age and major concomitant diseases. A negative association between coronary thrombosis and VTE in the univariate analysis (OR 0.7; 95% CI 0.6-0.8) (P < 0.001), was less pronounced in the multivariate analysis (OR 0.8; 95% CI 0.7-1.0) (P = 0.016). Conclusions: A positive association between atherothrombosis and VTE was confirmed, except in patients with coronary thrombosis, where IHD as competing death cause is a possible confounder. Our findings indicate a potential for directed prevention, but may also imply similarities in etiology.
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- Goudemand, J, et al.
(författare)
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Pharmacokinetic studies on Wilfactin((R)), a von Willebrand factor concentrate with a low factor VIII content treated with three virus-inactivation/removal methods
- 2005
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 3:10, s. 2219-2227
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In order to correct the primary von Willebrand factor (VWF) defect and avoid supra-physiologic plasma levels of factor VIII, a pure VWF concentrate almost devoid of FVIII was developed and used in France since 1989. Methods: The pharmacokinetic (PK) profile of the most recent version of this concentrate (Wilfactin (R); LFB, Les Ulis, France), treated with three virus-inactivation/removal methods (solvent/detergent, 35 nm filtration, dry heat treatment), was investigated in 25 patients. Seventeen patients with various types of clinically severe von Willebrand disease (VWD) were included in a crossover, randomized trial carried out in five European centers and comparing Wilfactin (R) with concentrates containing both FVIII and VWF (FVIII/VWF). Eight type 3 VWD patients were included in another trial carried out in six French centers comparing Wilfactin (R) with its previous version (Facteur Willebrand-LFB (R); LFB) that adopted one virus-inactivation method only. Results: For both the measurements evaluated in this study (VWF antigen, VWF:Ag; and VWF ristocetin co-factor activity, VWF:RCo), Wilfactin (R) had a PK profile similar to that of the FVIII/VWF concentrates and of Facteur Willebrand-LFB (R). VWF:RCo and VWF:Ag recoveries were 2.1 +/- 0.3 and 1.8 +/- 0.3 per IU kg(-1) respectively, and the half-lives were 12.4 +/- 1.8 and 15.9 +/- 1.5 h. The FVIII synthesis rate was 5.8 +/- 1.0 IU dL(-1) h(-1), with a half-life of 15.8 +/- 2.4 h. Conclusion: The PK of VWF and FVIII have not been altered by the three virus-inactivation/removal steps during the manufacturing of Wilfactin (R).
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