| 1. |
- Al-Shanqeeti, A, et al.
(författare)
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Protein Z and protein Z-dependent protease inhibitor - Determinants of levels and risk of venous thrombosis
- 2005
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 93:3, s. 411-413
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Tidskriftsartikel (refereegranskat)abstract
- To assess the potential roles of protein Z (PZ) and protein Z-dependent protease inhibitor (ZPI) in venous thrombosis, their plasma levels were measured in 426 individuals with venous thrombosis and 471 control individuals participating in the Leiden Thrombophilia Study. A relationship between the level of PZ or ZPI and venous thrombosis was not detected in the overall case-control study. PZ and ZPI circulate as a complex and their plasma levels are interdependent. Both PZ and ZPI are increased with oral contraceptive use and reduced with oral anticoagulant therapy.
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| 2. |
- Astermark, Jan, et al.
(författare)
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A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor.
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 109:Sep 21, s. 546-551
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Tidskriftsartikel (refereegranskat)abstract
- The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA (factor VIII inhibitor-bypassing activity), an activated prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor Vila (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. The FENOC study was designed to test equivalence of the products in the treatment of ankle, knee, and elbow joint bleeding. A prospective, open-label, randomized, crossover, equivalency design was used. The parameters of interest were the percentage of patients who reported efficacy in response to FEIBA and the percentage that reported efficacy in response to NovoSeven. A difference in these percentages of no more than 15% was determined to be a clinically acceptable magnitude for equivalence of the 2 products. The primary outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes contributed by 48 participants were analyzed. The criterion for declaring the 2 products equivalent at 6 hours was not met; however, the confidence interval of the difference in percentages of efficacy reported for each product only slightly exceeded the 15% boundary (-11.4%-15.7%), P=.059. FEIBA and NovoSeven appear to exhibit a similar effect on joint bleeds, although the efficacy between products is rated differently by a substantial proportion of patients. This trial was registered at www.clinicaltrials.gov as #NCT00166309.
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| 3. |
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| 4. |
- Astermark, Jan, et al.
(författare)
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Polymorphisms in the IL-10 but not in the IL-1{beta} and IL-4 genes are associated with inhibitor development in patients with hemophilia A.
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 107:8, s. 3167-3172
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the Malmö International Brother Study (MIBS) is to evaluate host genetic factors associated with the development of inhibitory antibodies in patients with hemophilia. Factor VIII gene mutations and genetic polymorphisms of the IL1beta, IL4, and 100 genes, known to influence antibody production in autoimmune diseases, were analyzed in 164 patients (124 with severe, 26 with moderate, and 14 with mild disease) in 78 unrelated families with hemophilia A. Seventy-seven (47%) patients in 54 families had a history of inhibitors (57 high responding, 20 low responding). Inversions were found in 36 families (75 patients). There was no association between the development of inhibitor and the IL1beta Taql RFLP alleles in exon 5 or the -590 C/T single nucleotide polymorphism (SNP) in the promoter region of IL4. There was, however, a strong association between an allele with 134 bp in one of the CA repeat microsatellites, IL10G, located in the promoter region of the IL10 gene, and the development of inhibitor (odds ratio [OR], 4.4; 95% confidence interval [95% CI], 2.1-9.5; P < .001). The association was consistent in the subgroup of families with severe hemophilia and inversions. IL10 is the first gene located outside the causative factor VIII gene mutation to be associated with inhibitor development.
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| 5. |
- Astermark, Jan, et al.
(författare)
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Polymorphisms in the TNFA gene and the risk of inhibitor development in patients with hemophilia A.
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 108:12, s. 3739-3745
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Tidskriftsartikel (refereegranskat)abstract
- The HLA class I/II alleles and the tumor necrosis factor alpha (TNFA) locus are closely linked in the MHC complex. We have characterized the causative factor VIII mutation, HLA alleles as well as 4 polymorphisms (-827C > T, -308G > A, -238A > G, and 670A > G) in the TNFA gene in 164 patients (124 severe, 26 moderate, and 14 mild) in 78 families with hemophilia A enrolled in the Malmo International Brother Study (MIBS). Inhibitors were identified in 77.8% of patients with a single haplotype (Hap 2) and 72.7% of the patients with the TNFA -308 A/A genotype within this haplotype compared with 39.70/6 for TNFA -308 G/G patients and 46.9% for TNFA -308 G/A heterozygotes (OR 4.0; 95% CI, 1.4-11.5; P = .008). The association between the -308 A/A genotype and inhibitors was enhanced in subgroups of patients with severe hemophilia (OR 19.2; 95% CI 2.4-156.5; P < .001) and with inversions (n = 75; OR, 11.8; 95% CI, 1.3-105.1; P = .013). Associations were found for the HLA A26 and B44 alleles, but these were not consistent in the subgroup analysis. Our data imply that the TNFA -308G > A polymorphism within Hap 2 is a useful marker and potential modulator of the immune response to replacement therapy in patients with hemophilia.
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| 6. |
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| 7. |
- Berntorp, Erik
(författare)
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Differential response to bypassing agents complicates treatment in patients with haemophilia and inhibitors.
- 2009
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 15, s. 41343-41343
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Tidskriftsartikel (refereegranskat)abstract
- Summary. The bypassing agents factor eight inhibitor bypassing activity (FEIBA) anti-inhibitor coagulant complex and recombinant activated factor VII (rFVIIa) have been established as safe and effective therapies for treating bleeding episodes in haemophilia patients with inhibitors. However, the efficacy of each bypassing agent can vary, and neither agent is universally effective. The reasons for such variability have yet to be confirmed, but may involve patient-specific factors and the mechanisms of action (MOAs) and pharmacokinetic profiles of these two agents. This issue underscores the necessity of both products in the comprehensive care of patients with haemophilia and inhibitors. The objective of this review is to discuss the evidence of a differential haemostatic response to bypassing agents and the potential roles of MOA and patient-specific factors in contributing to the differences in response.
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| 8. |
- Berntorp, Erik
(författare)
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Erik von Willebrand.
- 2007
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 120, s. 3-4
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Berntorp, Erik
(författare)
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Haemate P/Humate-P: a systematic review.
- 2009
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Ingår i: Thrombosis Research. - 1879-2472. ; 124 Suppl 1:Nov, s. 11-14
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Tidskriftsartikel (refereegranskat)abstract
- Haemate P/Humate-P, the first plasma-derived von Willebrand factor (VWF)/factor VIII (FVIII)-containing concentrate that was pasteurized to reduce the risk of virus infection, was developed in the 1970s and approved for use in Germany in 1981. Today, Haemate P is marketed in over 35 countries worldwide for on-demand treatment and long-term prophylaxis in patients with von Willebrand disease (VWD) or haemophilia A. With more than 25 years of clinical experience, Haemate P has demonstrated predictable pharmacokinetics, consistent haemostatic efficacy, and an excellent safety profile in paediatric and adult populations. Its VWF composition is quantitatively and qualitatively similar to that of normal plasma. The risk of virus transmission has been minimized, and treatment-related adverse events are rare. Only a very low incidence of thromboembolic events has been reported. Guidelines for dosing have been developed; optimal dosing depends on the goals of therapy, clinical setting, VWD type and severity, and other patient-related factors. Based on the extensive clinical experience with Haemate P, it has become the gold standard for replacement therapy in patients with VWD. Further studies will continue to explore its use in other clinical settings, including as immune tolerance induction therapy for patients with haemophilia A.
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| 10. |
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