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- Berntorp, Erik, et al.
(författare)
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Inhibitor treatment in haemophilas A and B: Summary statement for the 2006 International Consensus Conference
- 2006
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 12, s. 41281-41281
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Tidskriftsartikel (refereegranskat)abstract
- Participants in an international conference on the management of haemophilia patients with inhibitors developed a jointly authored summary of the findings and conclusions of the conference. Current knowledge of the genetic and immunologic mechanisms underlying inhibitor development was briefly summarized. Concerning the purported treatment-related risk factors, conference participants commented on the limitations of the available evidence and the need for more rigorous prospective research in a fully genotyped population. Other clinical considerations discussed included the unproved utility of routine surveillance, the need for assay standardization, the management of acute bleeding and approaches to joint disease prophylaxis and immune tolerance induction (ITI). A number of issues were identified as needing further investigation in larger prospective studies, ideally through international cooperation. Such studies should enrol cohorts that have been scrupulously defined in terms of mutation status and treatment exposure. Finally, conference participants urged their colleagues to participate in the currently ongoing international trials of ITI.
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| 2. |
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| 3. |
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| 4. |
- Clausen, Niels, et al.
(författare)
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Similar bleeding phenotype in young children with haemophilia A or B : A cohort study
- 2014
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 20:6, s. 747-755
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Tidskriftsartikel (refereegranskat)abstract
- The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL-1 respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A.
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| 5. |
- Eckhardt, CL, et al.
(författare)
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Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 122:11, s. 1954-1962
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Tidskriftsartikel (refereegranskat)abstract
- The inhibitor incidence in nonsevere hemophilia A patients with certain F8 mutations approaches the inhibitor incidence in severe patients. These findings are highly relevant for clinical practice, as they facilitate identification of high-risk patients based on F8 genotype.
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| 6. |
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| 7. |
- van Velzen, Alice S., et al.
(författare)
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Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients : Results of the INSIGHT case-control study
- 2017
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 15:7, s. 1422-1429
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Tidskriftsartikel (refereegranskat)abstract
- Essentials: Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk. Physicians need to review arguments for factor VIII dose and elective surgery extra critically. Summary: Background: Inhibitor development is a major complication of treatment with factor VIII concentrates in hemophilia. Findings from studies among severe hemophilia A patients suggest that intensive treatment episodes increase the risk of developing inhibitors. Objectives: We set out to assess whether intensive treatment is also associated with an increased risk of inhibitor development among non-severe hemophilia A patients. Patients/Methods: We performed a nested case-control study. A total of 75 inhibitor patients (cases) and 223 control patients were selected from 2709 non-severe hemophilia A patients (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for date of birth and cumulative number of exposure days (EDs) to FVIII concentrates. Conditional logistic regression was used to calculate both unadjusted and adjusted odds ratios (aOR); the latter were adjusted for a priori specified confounders. Results: Peak treatment of 5 or 10 consecutive EDs did not increase inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8; CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3) and a high mean dose (> 45 IU kg-1/ED) of FVIII concentrate (aOR, 7.5; CI, 1.6-35.6) were associated with an increased inhibitor risk. Conclusions: Our findings suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor development in non-severe hemophilia A. Together with the notion that non-severe hemophilia A patients are at a lifelong risk of inhibitor development, we suggest that in the future physicians will review the arguments for the FVIII dose and elective surgery extra critically.
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| 8. |
- Brackmann, H. H., et al.
(författare)
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Immune tolerance induction : What have we learned over time?
- 2018
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 24, s. 3-14
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Forskningsöversikt (refereegranskat)abstract
- Development of inhibitory antibodies to infused factor VIII (FVIII) concentrates continues to be the most serious complication of haemophilia A management. Induction of immune tolerance by administering high doses of FVIII concentrate (antigen) and prothrombin complex concentrates to control bleeding was originated in the 1970s in Bonn, Germany, by Dr Hans-Hermann Brackmann, and became known as the Bonn protocol. ITI transformed the life of the index patient, who was 19 years of age when he began treatment, and dramatically improved the medical landscape for all patients with haemophilia and inhibitors. Over the past 40 years, variations to the Bonn protocol have been proposed. All protocols are effective although some are better suited than others for use in certain situations. The specific molecular defect in FVIII and the human leucocyte antigen (HLA) type of an individual with haemophilia are major codependent determinants to inhibitor development. Given the range of potential molecular defects and the staggering number of potential HLA types, it is likely that treatment arms of randomized studies in haemophilia represent highly diverse populations, which reduces the power of a study to demonstrate differences between treatments. Although available clinical guidelines and consensus recommendations for ITI therapy are not always in complete agreement, collectively the guidelines provide a reasonable level of guidance for administering ITI therapy under different clinical scenarios. Several studies of ITI therapy are ongoing with the aim of clarifying unresolved issues in haemophilia management including the role of von Willebrand factor in inhibitor eradication.
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| 9. |
- Berntorp, Erik, et al.
(författare)
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Management of bleeding disorders in children
- 2012
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 18:Suppl. 2, s. 15-23
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Forskningsöversikt (refereegranskat)abstract
- Haemophilia, if not properly managed, can lead to chronic disease and lifelong disabilities. The challenges and issues in infants/young children are different from those in older children and adults although episodes of bleeding still predominate as the diagnostic trigger. Awareness of clinical manifestations and treatment complications are crucial in instituting appropriate management and implementing preventive strategies. Currently, inhibitor development is a challenging complication of paediatric haemophilia and prophylaxis is emerging as the optimal preventive care strategy. In this section we will review some important aspects of haemophilia in children including early prophylaxis, current evidence relating to inhibitor development, including the aims of the SIPPET study which is already ongoing and involves boys <6 years, and the potential of immune tolerance therapy for eradicating the inhibitor and permitting a resumption of standard dosing schedules.
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| 10. |
- Gouw, Samantha C., et al.
(författare)
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Factor VIII Products and Inhibitor Development in Severe Hemophilia A
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 368:3, s. 231-239
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Tidskriftsartikel (refereegranskat)abstract
- Background For previously untreated children with severe hemophilia A, it is unclear whether the type of factor VIII product administered and switching among products are associated with the development of clinically relevant inhibitory antibodies (inhibitor development). Methods We evaluated 574 consecutive patients with severe hemophilia A (factor VIII activity, <0.01 IU per milliliter) who were born between 2000 and 2010 and collected data on all clotting-factor administration for up to 75 exposure days. The primary outcome was inhibitor development, which was defined as at least two positive inhibitor tests with decreased in vivo recovery of factor VIII levels. Results Inhibitory antibodies developed in 177 of the 574 children (cumulative incidence, 32.4%); 116 patients had a high-titer inhibitory antibody, defined as a peak titer of at least 5 Bethesda units per milliliter (cumulative incidence, 22.4%). Plasma-derived products conferred a risk of inhibitor development that was similar to the risk with recombinant products (adjusted hazard ratio as compared with recombinant products, 0.96; 95% confidence interval [CI], 0.62 to 1.49). As compared with third-generation full-length recombinant products (derived from the full-length complementary DNA sequence of human factor VIII), second-generation full-length products were associated with an increased risk of inhibitor development (adjusted hazard ratio, 1.60; 95% CI, 1.08 to 2.37). The content of von Willebrand factor in the products and switching among products were not associated with the risk of inhibitor development. Conclusions Recombinant and plasma-derived factor VIII products conferred similar risks of inhibitor development, and the content of von Willebrand factor in the products and switching among products were not associated with the risk of inhibitor development. Second-generation full-length recombinant products were associated with an increased risk, as compared with third-generation products. (Funded by Bayer Healthcare and Baxter BioScience.)
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