| 1. |
- Berntorp, Erik, et al.
(författare)
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New Approaches to Using FEIBA in the Treatment of Inhibitor Patients.
- 2006
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 1098-9064 .- 0094-6176. ; 32:Suppl 2, s. 22-27
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Tidskriftsartikel (refereegranskat)abstract
- Managing hemophilia becomes particularly difficult in patients with inhibitory antibodies, especially in those requiring surgery or with refractory bleeding events. Equally challenging are those patients who develop autoantibodies against factor VIII (FVIII) in the absence of a prior history of FVIII deficiency (acquired hemophilia). Physicians seeking both short- and long-term treatment strategies for bleeding events must often rely on FVIII-bypassing agents such as activated prothrombin complex concentrate (e.g., factor eight bypassing activity [FEIBA VH, Baxter BioScience, Westlake Village, CA]) or recombinant factor VIIa (rFVIIa [NovoSeven, NovoNordisk, Bagsvaerd, Denmark]). Surgical procedures in patients with inhibitors present a considerable challenge, from both a risk-benefit and a cost-benefit aspect. Hemostasis is difficult to achieve in these patients and new treatment options are being explored. Similarly challenging are refractory bleeds, the management of which is likely to benefit from a systematic treatment approach.
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| 2. |
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| 3. |
- Leissinger, Cindy, et al.
(författare)
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Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors
- 2011
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 365:18, s. 1684-1692
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Effective strategies to prevent bleeding in such patients have not yet been established. Methods We enrolled patients with hemophilia A who were older than 2 years of age, had high-titer inhibitors, and used concentrates known as bypassing agents for bleeding in a prospective, randomized, crossover study comparing 6 months of anti-inhibitor coagulant complex (AICC), infused prophylactically at a target dose of 85 U per kilogram of body weight (+/- 15%) on 3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a target dose of 85 U per kilogram [+/- 15%] used for bleeding episodes). The two treatment periods were separated by a 3-month washout period, during which patients received on-demand therapy for bleeding. The primary outcome was the number of bleeding episodes during each 6-month treatment period. Results Thirty-four patients underwent randomization; 26 patients completed both treatment periods and could be evaluated per protocol for the efficacy analysis. As compared with on-demand therapy, prophylaxis was associated with a 62% reduction in all bleeding episodes (P < 0.001), a 61% reduction in hemarthroses (P < 0.001), and a 72% reduction in target-joint bleeding (>= 3 hemarthroses in a single joint during a 6-month treatment period) (P < 0.001). Thirty-three randomly assigned patients received at least one infusion of the study drug and were evaluated for safety. One patient had an allergic reaction to the study drug. Conclusions AICC prophylaxis at the dosage evaluated significantly and safely decreased the frequency of joint and other bleeding events in patients with severe hemophilia A and factor VIII inhibitors. (Funded by Baxter BioScience; Pro-FEIBA ClinicalTrials.gov number, NCT00221195.)
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| 4. |
- Negrier, Claude, et al.
(författare)
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Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:10, s. 2695-2701
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Tidskriftsartikel (refereegranskat)abstract
- Replacement therapy with factor IX (FIX) concentrates is the recommended treatment for patients with hemophilia B, an X-linked bleeding disorder occurring in 1: 25 000 male births. N9-GP is a recombinant FIX molecule with a prolonged half-life which is obtained by site-directed glycoPEGylation where a 40-kDa polyethylene glycol molecule is attached to the activation peptide of FIX. This first human dose trial in patients with hemophilia B investigated the safety and pharmacokinetic properties of a single IV dose of N9-GP. Sixteen previously treated patients received one dose of their previous FIX product followed by one dose of N9-GP at the same dose level (25, 50, or 100 U/kg). None of the patients developed inhibitors. One patient developed transient hypersensitivity symptoms during administration of N9-GP and was excluded from pharmacokinetic analyses. In the remaining 15 patients, N9-GP was well-tolerated. The half-life was 93 hours, which was 5 times higher than the patient's previous product. The incremental recovery of N9-GP was 94% and 20% higher compared with recombinant and plasma-derived products, respectively. These results indicate that N9-GP has the potential to reduce dosing frequency while providing effective treatment of bleeding episodes with a single dose. The trial was registered at www.clinicaltrials.gov as NCT00956345. (Blood. 2011;118(10):2695-2701)
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| 5. |
- Negrier, Claude, et al.
(författare)
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Surgical evaluation of a recombinant factorVIII prepared using a plasma/albumin-free method: Efficacy and safety of Advate in previously treated patients
- 2008
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 100:2, s. 217-223
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of factor F(V)III replacement in patients with haemophilia A undergoing surgery is critical for FVIII concentrates, yet large scale, multi-center prospective studies, particularly using continuous infusion, are generally lacking for new products. This study evaluated efficacy and safety of a newly developed recombinant FVIII (rAHF-PFM) administered by bolus or continuous infusion in haemophilia A patients undergoing surgery. Subjects >= 5 years of age with baseline FVIII:C <= 2%, and >= 150 prior FVIII exposure days were included in this prospective, international, open-label, uncontrolled clinical trial. rAHF-PFM was administered perioperatively by bolus infusion (BI) or continuous infusion (CI) according to the standard use at the center to prevent bleeding complication. Both the surgeon and haematologist rated efficacy during hospitalization. Fifty-eight subjects underwent 65 surgical procedures (22 major haemorrhagic risk; 35 minor, 8 dental procedures). Bolus infusion was used exclusively in 47 procedures and continuous infusion, with or without supplemental bolus infusions, in 18. Haemostatic efficacy was assessed as excellent or good for 100% of intraoperative ratings (17 CI, 44 BI, 61 total procedures), and 100% of postoperative ratings performed at time of discharge (18 CI, 44 BI, 62 total procedures). Median total consumption of rAHF-PFM during hospitalization was 822 IU/kg/surgery with CI and 910 IU/kg/surgery with BI. Overall rAHF-PFM was well tolerated, and FVIII inhibitors were not detected. In conclusion, rAHF-PFM administered via continuous infusion or bolus injections is safe, non-immunogenic, and effective for perioperative hemostatic management in previously treated haemophilia A patients.
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| 6. |
- Samuelson Bannow, Bethany, et al.
(författare)
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Factor VIII : Long-established role in haemophilia A and emerging evidence beyond haemostasis
- 2019
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Ingår i: Blood Reviews. - : Elsevier BV. - 0268-960X. ; 35, s. 43-50
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Forskningsöversikt (refereegranskat)abstract
- Factor VIII protein (FVIII) as a coagulation replacement factor has for decades been used as the standard of care for management of people with haemophilia A. It is effective for treatment of bleeding events, as prophylaxis to prevent bleeding events and preserve joint function, and to support surgery in people with haemophilia A. Despite long experience in treating haemophilia A, we are only beginning to understand the functions of FVIII beyond its established role as a coenzyme to factor IXa to expedite thrombin generation through the intrinsic pathway of coagulation. Here, we review the current role of FVIII coagulant (FVIII:C) in haemophilia A management and emerging evidence for the role of FVIII across multiple systems, including the cardiovascular system, angiogenesis and maintenance of bone health. For instance, supraphysiological FVIII levels are a risk factor for venous thromboembolism. von Willebrand factor (VWF), which forms a non-covalent complex with circulating FVIII, is an established marker and regulator of angiogenesis. In a mouse model of haemophilia, treatment with FVIII decreased expression of receptor activator of nuclear factor kappa-Β ligand (RANKL), a marker for bone turnover. Longitudinal follow-up data in people with haemophilia A are needed to confirm and extend these observations.
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