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| 2. |
- Berntorp, Erik, et al.
(author)
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Third Åland islands conference on von Willebrand disease, 26-28 September 2012: meeting report.
- 2013
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In: Haemophilia. - : Wiley. - 1351-8216. ; 19 Suppl 3, s. 1-18
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Journal article (peer-reviewed)abstract
- The first meeting of international specialists in the field of von Willebrand disease (VWD) was held in the Åland islands in 1998 where Erik von Willebrand had first observed a bleeding disorder in some members of a family from Föglö and a summary of the meeting was published in 1999. The second meeting was held in 2010 and a report of the meeting was published in 2012. Topics covered included progress in understanding of VWD over the last 50 years; multimers; classification of VWD; pharmacokinetics and laboratory assays; genetics; treating the paediatric patient; prophylaxis; geriatrics; gene therapy and treatment guidelines. This third meeting held over 3 days covered the structure and function of von Willebrand factor (VWF); type 1 VWD, the most common form of the disease; a lifespan of pharmacokinetics in VWD; detecting inhibitors in VWD patients; and special challenges in understanding and treating the female VWD patient.
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| 3. |
- Astermark, Jan, et al.
(author)
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Managing Haemophilia for Life: 4th Haemophilia Global Summit
- 2014
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In: Haemophilia. - : Wiley. - 1351-8216. ; 20, s. 1-20
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Research review (peer-reviewed)abstract
- The 4th Haemophilia Global Summit was held in Potsdam, Germany, in September 2013 and brought together an international faculty of haemophilia experts and delegates from multidisciplinary backgrounds. The programme was designed by an independent Scientific Steering Committee of haemophilia experts and explored global perspectives in haemophilia care, discussing practical approaches to the optimal management of haemophilia now and in the future. The topics outlined in this supplement were selected by the Scientific Steering Committee for their relevance and potential to influence haemophilia care globally. In this supplement from the meeting, Jan Astermark reviews current understanding of risk factors for the development of inhibitory antibodies and discusses whether this risk can be modulated and minimized. Factors key to the improvement of joint health in people with haemophilia are explored, with Carlo Martinoli and Victor Jimenez-Yuste discussing the utility of ultrasound for the early detection of haemophilic arthropathy. Other aspects of care necessary for the prevention and management of joint disease in people with haemophilia are outlined by Thomas Hilberg and Sebastian Lobet, who highlight the therapeutic benefits of physiotherapy and sports therapy. Riitta Lassila and Carlo-Federico Perno describe current knowledge surrounding the risk of transmission of infectious agents via clotting factor concentrates. Finally, different types of extended half-life technology are evaluated by Mike Laffan, with a focus on the practicalities and challenges associated with these products.
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| 4. |
- Eckhardt, CL, et al.
(author)
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Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A
- 2013
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 122:11, s. 1954-1962
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Journal article (peer-reviewed)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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| 5. |
- Ljung, Rolf, et al.
(author)
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Novel coagulation factor concentrates: Issues relating to their clinical implementation and pharmacokinetic assessment for optimal prophylaxis in haemophilia patients.
- 2013
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In: Haemophilia. - : Wiley. - 1351-8216. ; 19:4, s. 481-486
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Research review (peer-reviewed)abstract
- Prophylaxis is considered the optimal treatment regimen for patients with severe haemophilia, and may be especially important in the prevention of joint disease. Novel coagulation factor concentrates with prolonged half-lives promise to improve patient treatment by enabling prophylaxis with less frequent dosing. With the call to individualize therapy in haemophilia, there is growing awareness of the need to use pharmacokinetic (PK) assessments to tailor prophylaxis. However, for new factor concentrates, it is not yet known which PK values will be most informative for optimizing prophylaxis. This topic was explored at the Eighth Zurich Haemophilia Forum. On the basis of our clinical experience and a discussion of the literature, we report key issues relating to the PK assessment of new coagulation factors and include suggestions on the implementation of PK data to optimize therapy. As both inter- and intra-individual variability in factor half-life have been reported, we suggest that frequent PK assessments should be conducted. However, to diminish the burden of more frequent sampling, sparser sampling strategies and the use of population modelling should be considered. Guidelines on how to assay new factor concentrates, and which PK parameters should be measured, are needed. Concerns were raised regarding the possibility of breakthrough bleeding, and current thinking on how to prevent breakthrough bleeding may no longer be appropriate. Finally, as treatment adherence may be more important to ensure that a therapeutic level of a new coagulation factor concentrate is maintained, behavioural techniques could be implemented to help to improve treatment adherence.
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| 6. |
- Rodriguez-Merchan, E. C., et al.
(author)
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Joint protection in haemophilia
- 2011
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In: Haemophilia. - : Wiley. - 1351-8216. ; 17, s. 1-23
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Journal article (peer-reviewed)abstract
- Haemarthroses (intra-articular haemorrhages) are a frequent finding typically observed in patients with haemophilia. Diagnosis and treatment of these bleeding episodes must be delivered as early as possible. Additionally, treatment should ideally be administered intensively (enhanced on-demand treatment) until the resolution of symptoms. Joint aspiration plays an important role in acute and profuse haemarthroses as the presence of blood in the joint leads to chondrocyte apoptosis and chronic synovitis, which will eventually result in joint degeneration (haemophilic arthropathy). Ultrasonography (US) is an appropriate diagnostic technique to assess the evolution of acute haemarthrosis in haemophilia, although magnetic resonance imaging remains the gold standard as far as imaging techniques are concerned. Some patients experience subclinical haemarthroses, which eventually tend to result in some degree of arthropathy, especially in the ankles. Nowadays, the most effective way of protecting these patients is primary prophylaxis, which in practice changes severe haemophilia into moderate haemophilia, preventing or at least minimizing the occurrence of haemarthrosis. If primary prophylaxis is, for whatever reason not an option, secondary prophylaxis and enhanced on demand treatment should be considered. Two alternatives are available for inhibitor patients: (i) control of haemostasis using by-passing agents (rFVIIa or aPCCs) either as enhanced on demand treatment or secondary prophylaxis, as appropriate, following the same basic principles used for non-inhibitor patients and (ii) immune tolerance induction (ITI) to eradicate the inhibitor.
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| 7. |
- Rodriguez-Merchan, E. C., et al.
(author)
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Prevention of haemophilic arthropathy during childhood. May common orthopaedic management be extrapolated from patients without inhibitors to patients with inhibitors?
- 2008
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In: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 14:Suppl. 6, s. 68-81
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Journal article (peer-reviewed)abstract
- We recommend prophylaxis in haemophilic children with an inhibitor as a way of preventing the musculoskeletal impairment that is likely to affect them. This approach has been used for children without inhibitors with excellent results. If prophylaxis is not feasible, we suggest that intensive on-demand treatment should be given. Two agents, recombinant activated FVII (rFVIIa) and activated prothrombin complex concentrates (aPCC), are currently used to control haemostasis either for prophylaxis or intensive on-demand treatment. As it is recombinant, rFVIIa would seem more appropriate to be employed in children. aPCC could be used in adults, or in the event of an unsatisfactory response to rFVIIa. We recommend prophylaxis or, at least, intensive on-demand treatment in haemophilia children with inhibitors. Both rFVIIa and aPCC are being used for this purpose. It would seem that rFVIIa might be more appropriate for children as it is a recombinant product. Nevertheless, after skeletal maturity (in adults), both agents could be used indistinctively (taking into consideration that FEIBA is a plasma-derived product). We still need more well-designed comparative studies in order to be able to assert that our consensus-based conclusion is evidence based. In orthopaedic surgery, both aPCC and rFVIIa have been reported to be effective in controlling perioperative haemostasis, although in practice most centres have so far used rFVIIa for their orthopaedic procedures. We recommend rehabilitation programmes for all patients with inhibitors in order to mitigate the disabling and handicapping impact of their condition and thereby enable them to achieve social integration. Programmes for haemophilic children without inhibitors can be applied to children with inhibitors but should be individually tailored.
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| 8. |
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| 9. |
- Santagostino, E., et al.
(author)
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Paediatric haemophilia with inhibitors: existing management options, treatment gaps and unmet needs
- 2009
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In: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 15:5, s. 983-989
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Research review (peer-reviewed)abstract
- Development of inhibitors is a severe complication of haemophilia posing many management challenges. While a long-term goal in inhibitor patients is eradication of inhibitors through immune tolerance induction, bypassing agents such as recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (aPCC) are essential for control of bleeding episodes. Paediatric patients with haemophilia and inhibitors are at particular risk of recurrent haemarthroses, and management of these patients should seek to avoid joint damage and support the child's full social and physical development. Current options for management of bleeding complications include on-demand treatment of acute bleeding episodes, secondary prophylaxis to avoid recurrent bleeds and surgery to treat affected joints. There is also a rationale for adopting prophylactic approaches to prevent bleeding in inhibitor patients, allowing this group similar opportunities for protection against arthropathy development as are given to non-inhibitor patients. This paper, based on a roundtable meeting of haematology experts at the first Zurich Haemophilia Forum in May 2008, reviews the current evidence supporting more intense and prophylactic approaches to manage bleeding risk in paediatric haemophilia patients with inhibitors, and highlights the need for investigations of primary prophylaxis in this vulnerable patient group, to support best long-term outcome.
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