| 1. |
- 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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| 2. |
- Santagostino, E., et al.
(författare)
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Paediatric haemophilia with inhibitors: existing management options, treatment gaps and unmet needs
- 2009
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 15:5, s. 983-989
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Forskningsöversikt (refereegranskat)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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| 3. |
- Rodriguez-Merchan, E. C., et al.
(författare)
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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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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 14:Suppl. 6, s. 68-81
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Tidskriftsartikel (refereegranskat)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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