| 31. |
- Donfield, Sharyne M., et al.
(författare)
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Delays in maturation among adolescents with hemophilia and a history of inhibitors
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 110:10, s. 3656-3661
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitory antibodies to factors VIII or IX have the potential to affect a broad range of outcomes among people with hemophilia; however, their possible effect on growth and maturation has not been explored. We evaluated skeletal maturation (bone age), pubertal progression, serum testosterone levels, height velocity, and stature in the multicenter Hemophilia Growth and Development Study. A total of 333 children and adolescents (mean age, 12.4 years) were enrolled from 1989 to 1990 and followed for 7 years. Of these, 18% (n = 60) had a history of inhibitors. Bone age among HIV- adolescents with a history of inhibitors lagged 9 or more months behind those without inhibitors at every age from 12 to 15 years. Those with a history of inhibitors were older at every Tanner stage transition, attained a lower maximum growth velocity, and their serum testosterone levels were significantly lower compared with those without inhibitors. Delays were greater among HIV+ patients with a history of inhibitors compared with those without inhibitors; however, the differences were generally small and not statistically significant. The results of this investigation underscore the importance of monitoring the growth and maturation of children and adolescents with hemophilia, particularly those with inhibitors.
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| 32. |
- Donfield, S. M., et al.
(författare)
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Value added: increasing the power to assess treatment outcome in joint haemorrhages
- 2008
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 14:2, s. 276-280
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Tidskriftsartikel (refereegranskat)abstract
- Subject reports of efficacy of treatment of haemophilia-related joint bleeding are by definition subjective, yet are often the primary outcome in studies comparing therapies. Verbal descriptors such as effective, partially effective, poorly effective, not effective are treated as dichotomous or categorical variables in analyses, lowering the statistical power relative to that which might be achieved with a continuous variable. The aims of this study were to examine reports of pain recorded on a 100-mm visual analogue scale (VAS) during the course of joint bleeding; determine whether pain varied by treatment period among pairs reporting discordant outcomes on a verbal scale (one product effective, the other not effective); test whether the two products under study were equivalent with respect to VAS scores; and evaluate their relationship to verbal reports of efficacy. Data from the international, prospective, randomized, crossover FEIBA NovoSeven Comparative study of two bypassing agents used for treatment of 96 bleeding episodes in 48 participants were examined. VAS scores were associated with verbal descriptors of efficacy at every time point, and were equivalent between treatment periods. There were differences in mean scores at time points at which participants rated one treatment effective, the other not effective. As a continuous variable, the VAS score may have more power than a dichotomous variable and when used with verbal descriptions of efficacy can improve the overall accuracy of assessment. This report highlights an important consideration in the selection of outcome measurement that can be generalized to other haemophilia treatment research.
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| 33. |
- Federici, AB, et al.
(författare)
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Von Willebrand's disease: clinical management
- 2006
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 12:s3, s. 152-158
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Tidskriftsartikel (refereegranskat)abstract
- The aim of treatment of von Willebrand's disease (VWD) is to correct the dual defect of haemostasis, i.e. the abnormal platelet adhesion due to reduced and/or dysfunctional von Willebrand factor (VWF) and the abnormal coagulation expressed by low levels of factor VIII (FVIII). Desmopressin (DDAVP) is the treatment of choice for type 1 VWD because it can induce release of normal VWF from cellular compartments. Prospective studies on biological response versus clinical efficacy of DDAVP in VWD type 1 and 2 are in progress to further explore its benefits and limits as therapeutic option. In type 3 and in severe forms of type 1 and 2 VWD, DDAVP is not effective and for these patients plasma virally inactivated concentrates containing VWF and FVIII are the mainstay of treatment. Several intermediate- and high-purity VWF/FVIII concentrates are available and have been shown to be effective in clinical practice (bleeding and surgery). New VWF products almost devoid of FVIII are now under evaluation in clinical practice. Although thrombotic events are rare in VWD patients receiving repeated infusions of concentrates, there is some concern that sustained high FVIII levels may increase risk of postoperative venous thromboembolism. Dosage and timing of VWF/FVIII administrations should be planned to keep FVIII level between 50 and 150 U/dL. Appropriate dosage and timing in repeated infusions are also very important in patients exposed to secondary long term prophylaxis for recurrent bleedings.
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| 34. |
- Franchini, M, et al.
(författare)
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Tyr2105Cys mutation in exon 22 of FVIII gene is a risk factor for the development of inhibitors in patients with mild/moderate haemophilia A
- 2006
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 12:4, s. 448-451
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Tidskriftsartikel (refereegranskat)abstract
- We report the case of a patient with mild haemophilia A, due to a Tyr2105Cys mutation in exon 22 of the C1 domain, who developed a high-titre factor VIII inhibitor (maximum titre 1600 BU) with recurrent severe haemorrhages and fatal intracranial bleeding. Based on published data, it appears that although this mutation occurs rarely in patients with mild or moderate haemophilia A, it is frequently associated with the development of high-titre inhibitors.
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| 35. |
- 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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| 36. |
- Hamad, R. Rafik, et al.
(författare)
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Increased thrombin generation in women with a history of preeclampsia
- 2009
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 123:4, s. 580-586
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Women with a history of preeclampsia have an increased risk for cardiovascular disease in later Life. We evaluated thrombogenic characteristics of women with a previous history of preeclampsia, expressed in levels of thrombin generation, number of micropartictes and related to menstrual cycle and endothelial function, measured as flow-mediated dilatation. Materials and methods: We included 18 primipara women with a history of preeclampsia and 17 healthy primipara controls, 15 (+/- 3) months after the index pregnancy. Thrombin generation was measured by tissue factor triggered assay, microparticle levels were measured by flow cytometry and the endothelial function was previously examined by measuring flow-mediated dilatation by high-resotution ultrasound, during follicular and luteal phases of the menstrual cycle. Results: Women with previous preeclampsia produced more total amount of thrombin as calculated from thrombin max, thrombin potential and max slope levels p<0.05, 0.01 and 0.01 respectively. Platelet derived microparticle levels were higher in women with a history of preeclampsia, p=0.07. Flow-mediated dilatation was significantly decreased in comparison to healthy controls (p<0.0001). There were no variation in levels of thrombin, microparticies and flow-mediated dilatation during the menstrual phases. Conclusion: Women with a history of preectampsia show signs of hypercoagutability as indicated by higher thrombin generation and higher platelet derived microparticle levels. Since these women were investigated more than one year after delivery, these results may be indicative of an increased risk of cardiovascular events later in life. (c) 2008 Elsevier Ltd. Alt rights reserved.
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| 37. |
- Khawaji, Mohammed, et al.
(författare)
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Long-term prophylaxis in severe haemophilia seems to preserve bone mineral density.
- 2009
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 15:1, s. 261-266
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Tidskriftsartikel (refereegranskat)abstract
- It has been previously shown that patients with severe haemophilia and not receiving any prophylactic treatment render a high risk of reduced bone mineral density. The purpose of this study was to evaluate bone mineral density (BMD) in patients with haemophilia of different severity types and treatment. The study group consisted of 26 patients with severe haemophilia (aged 33.6 +/- 2.1) and 16 patients with mild haemophilia (aged 40.2 +/- 3.3). The BMD (g cm(-2)) was measured by dual-energy X-ray absorptiometry (DXA). Physical activity was assessed by a self-report questionnaire. Physical activity was scored as duration (h week(-)) and as metabolic physical activity score by weighing the intensity (MET-h week(-1)). Joints were evaluated according to a physical examination score. There was no significant difference in BMD at lumbar spine L1-L4 (mild, 1.214 vs. severe, 1.175; P = 0.329), total hip (1.085 vs. 1.001, P = 0.114), femoral neck (1.036 vs. 0.977, P = 0.265), trochanter (0.896 vs. 0.820, P = 0.131) and whole body (1.215 vs. 1.183, P = 0.325) between those with mild and severe haemophilia. Based on Z-score, both groups had normal BMD (Z score >-1). In patients with severe haemophilia, there was a significant correlation between joint evaluation score and BMD at total hip (P < 0.0001), femoral neck (P = 0.0003) and trochanter (P = 0.003). Physical activity did not correlate to disease severity. We did not observe a correlation between BMD and severity of haemophilia. The results indicate that the use of factor prophylaxis since early childhood may preserve normal BMD in severe haemophilia.
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| 38. |
- Lippert, Barbara, et al.
(författare)
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Cost effectiveness of haemophilia treatment: a cross-national assessment.
- 2005
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 16:7, s. 477-485
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the incremental cost effectiveness of on-demand versus prophylactic haemophilia therapy in Germany, Sweden, the United Kingdom and The Netherlands from the third-party payers' perspective. Using a decision tree model, the cost effectiveness of on-demand versus prophylactic therapy was analysed by extrapolating data from the European Haemophilia Economic Study to a 1-year analytic time horizon. Five hundred and six patients with severe haemophilia A and B, without inhibitors and at least 14 years of age, were enrolled in this study. Patients treated prophylactically had fewer bleeds than patients treated on-demand. With prophylactic treatment, the incremental cost per avoided bleeding ranged from [Euro sign]6650 for patients 30 years of age or younger in Germany to [Euro sign]14 140 for patients over 30 years old in Sweden. If quality of life was taken into account, patients receiving prophylactic treatment had higher mean utilities than patients on on-demand therapy. The incremental effectiveness ratios in Germany were [Euro sign]1.2 million per quality-adjusted life year gained for patients 30 years or younger and HIV-positive and [Euro sign]2.2 million for patients 30 years or younger and HIV-negative. In the group aged over 30 years and HIV-positive the on-demand treatment strategy was dominant, whereas in the over 30 years/HIV-negative group the incremental cost-utility ratio was [Euro sign]4.7 million per quality-adjusted life year. Based on our decision analysis, the use of prophylactic treatment was overall more effective than on-demand therapy in young haemophiliacs, but at extremely high cost.
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| 39. |
- Lundin, Björn, et al.
(författare)
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Gadolinium Contrast Agent is of Limited Value for Magnetic Resonance Imaging Assessment of Synovial Hypertrophy in Hemophiliacs.
- 2007
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Ingår i: Acta Radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 48:5, s. 520-530
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine the influence of different doses of gadolinium contrast agent on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of synovial hypertrophy and radiographic joint changes in hemophiliacs, and to investigate the value of gadolinium in MRI assessment of synovial hypertrophy in hemophiliacs using dynamic MRI and MRI scoring. Material and Methods: Twenty-one hemophiliacs on prophylactic factor treatment without recent bleeds were subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the patients, the MRI procedure was repeated after a triple dose of gadoteridol. Results: MRI findings of synovial hypertrophy were significantly correlated with Pettersson radiographic scores. In 19 of the 21 MRI investigated joints, administration of contrast agent did not alter the result of the evaluation of synovial hypertrophy. Conclusion: The optimal time interval for volume assessment of synovial hypertrophy after injection of gadolinium contrast agent is dose dependent. Hemophiliacs without recent bleeds have minor to abundant synovial hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is not routinely indicated for MRI scoring of joints in hemophiliacs.
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| 40. |
- Magnusson, Marie, et al.
(författare)
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Effects of pentoxifylline and its metabolites on platelet aggregation in whole blood from healthy humans
- 2008
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 581:3, s. 290-5
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Tidskriftsartikel (refereegranskat)abstract
- It is known that pentoxifylline inhibits platelet aggregation in vitro, but the effects from pentoxifylline and its main metabolites: 3,7-dimetyl-1(5 hydroxyhexyl)xanthine (R-M1 and S-M1), 3,7-dimetyl -1(4-carboxybutyl)xanthine (M4), 3,7-dimetyl -1(3-carboxypropyl)xanthine (M5), on platelet aggregation in whole blood in vitro and in vivo have not been studied. We found that pentoxifylline, rac-M1, R-M1, S-M1 and M4 significantly inhibit ADP induced platelet aggregation in whole blood in vitro in a concentration-dependent manner, R-M1 being the most potent followed by rac-M1, S-M1, pentoxifylline, and M4. In this series of experiments the effects on aggregation induced ATP-release were less pronounced and were only significant after treatment with pentoxifylline, rac-M1 and R-M1, but the potency order appears to be the same. Since the metabolites are not available for use in humans, and also since each substance would be extensively metabolised in vivo, we made an attempt to estimate the relative contribution of each substance to the total effect of pentoxifylline in vivo. Previously published concentrations of pentoxifylline and these metabolites in humans, after administration of pentoxifylline, were used in combination with the potency ratios from this study. The findings from these calculations were that the main effect in vivo comes from S-M1 followed by pentoxifylline, the other metabolites contribute less than 10% each. In conclusion: in the following potency order R-M1, rac-M1, pentoxifylline, S-M1 and M4 all have significant effects on platelet aggregation in whole blood in vitro. However, it appears that the main effects in vivo are caused by S-M1 and pentoxifylline.
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