Systematic review of efficacy of rFVIIa and aPCC treatment for hemophilia patients with inhibitors (original) (raw)
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Advances in clinical and experimental medicine : official organ Wroclaw Medical University
The development of inhibitors is the most severe complication of treating hemophilia patients with Factor VIII or IX, and providing effective hemostasis for inhibitor patients is challenging. Patients with high responding inhibitors (titer >5 BU/mL) are usually treated with recombinant activated Factor VII (rFVIIa), 90-120 microg/kg every 2-3 hours, or plasma-derived activated prothrombin complex concentrate. The aim of this study was to assess the efficacy and safety of a single dose of 270 microg/kg rFVIIa in inhibitor patients with joint or soft tissue bleeds treated at the Department of Paediatric Hematology and Oncology and the Department of Hematology and Transplantology. 7 inhibitor patients (3 adults aged 23-33 and 4 children aged 3-14) were included in the study. The hemostatic efficacy and tolerability of a single high dose of rFVIIa for home treatment of moderate or severe bleeds was evaluated. Treatment with rFVIIa effectively stopped bleeding in all patients without ...
Haemophilia, 2009
Summary. The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 μg kg−1 rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg−1 aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h.
Haemophilia, 2007
Haemophilia patients with inhibitors can develop bleeding episodes, which are refractory to monotherapy with either recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrates (APCC). Management of such bleeds is often difficult. We previously reported the safety of using a combination of rFVIIa and APCC given in sequential fashion. In this report, we update our experience with sequential therapy. A retrospective review of medical records was conducted including all reports of sequential therapy defined as receiving both rFVIIa and APCC within 6 h. Data extracted included demographic data, treatment prior to and following hospital admission, clinical data including type and location of bleed, response to therapy, physical examination and laboratory data. In addition, for some patients, thromboelastography was performed to document the effect of sequential therapy on clot formation characteristics. Four patients comprising 35 admissions, 209 hospital days and 115 days of sequential therapy were included in the updated dataset. No patient developed thrombosis or overt disseminated intravascular coagulation (DIC) although elevations in the D-dimer above 5 lg mL)1 were noted in 42% of the courses that lasted >3 days. Efficacy is suggested by the fact that patients had resolution of their bleeds after a median of 3 days of sequential therapy after failing to respond to a median of 3 days of monotherapy. Thromboelastography demonstrated an additive effect. Sequential therapy is a safe, potentially efficacious approach in the management of refractory bleeding episodes in patients with haemophilia and inhibitors.
International Journal of Hematology, 2001
A multicenter and open-labeled clinical trial of human recombinant factor VIIa (rFVIIa) was conducted in Japanese patients with severe hemophilia A or B with inhibitors. The trial consisted of 2 parts. In study 1, the pharmacokinetics, pharmacodynamics, and safety of a single dose of 120 µg/kg of rFVIIa were investigated in 8 patients. In the subsequent study 2, the hemostatic effect and safety of rFVIIa were evaluated during a 24-week period in 10 patients. In study 1, the mean maximum FVII-coagulant activity (FVII:C) was found to occur after 10 minutes; activity then decreased rapidly and returned to the baseline within 24 hours after a single intravenous infusion of rFVIIa. The mean half-life of FVII:C was 3.5 hours. The activated partial thromboplastin time and prothrombin time in the patients were immediately shortened but returned to the baseline within 24 hours after dosing. In study 2, 86 µg/kg to 120 µg/kg of rFVIIa (mean, 97 µg/kg) was administered 1 to 85 times to 10 patients. A total of 58.0% (91/157) of bleeding episodes were treated excellently or effectively, with 5 (3.2%) ineffective episodes. There was no apparent trend in the relationship of the hemostatic effect with bleeding sites, mean dose, or number of injections. The efficacy rate, however, was significantly higher (90.0%) in bleeding episodes treated within 3 hours than in those treated at longer intervals (31.0%). No treatment-related adverse events were observed, and there was no evidence of antibody formation to rFVIIa. In conclusion, rFVIIa is an effective and well-tolerated option for treatment of bleeding episodes in hemophilia patients with inhibitors.
Haemophilia, 2009
Several studies have suggested that recombinant factor VIIa (rFVIIa) is effective and safe at doses >90 lg kg)1. In March 2007, the European Medicines Agency approved the use of single-dose rFVIIa 270 lg kg)1 for the treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors. The aim of this study was to describe the use of singledose rFVIIa in a real-life setting. In November 2007, seven haemophilia specialists from five European countries convened to share and discuss their experiences with the single-dose rFVIIa regimen within haemophilia A. Case histories of eight patients were discussed in this retrospective study. Six adult and two paediatric patients (age range, 19 months-40 years) were treated with single-dose rFVIIa for a variety of target-joint bleeding, other bleeds and bleeding prevention. Treatment was successful in all the eight cases, with most patients requiring one dose to achieve bleeding resolution. No thrombotic or other safety concerns were raised by single-dose rFVIIa treatment. All patients and physicians preferred single-dose rFVIIa treatment to multiple injections; key benefits of single-dose rFVIIa treatment reported by patients and physicians included improved quality of life, greater convenience and ease of administration, improved compliance, faster control of bleeding, less injection-related pain and faster pain relief. In the patients reported here, single-dose rFVIIa 270 lg kg)1 appears to be an effective and safe haemostatic treatment that improves the quality of life and convenience of treatment for patients. Such treatment might be of particular benefit for patients with difficult venous access or needle phobia.
Iranian Red Crescent Medical Journal, 2014
Context: Mild-to-moderate bleeding disorders in haemophilia are primarily treated via recombinant activated factor VII a (rFVIIa) or activated prothrombin complex concentrate (aPCC). However, the efficacy of each bypassing agents may vary and none of them is universally effective. Evidence Acquisition: After reviewing the databases of PubMed, Scopus, MD Consult, Ovid, Trip database, Google Scholar, ProQuest and the Cochrane Library, finally, 17 papers published from 2000 to 2013 were extracted. We used as a random effect model in meta-analysis. Comprehensive meta-analysis (CMA) software was used for calculating and estimating the mean of bleeding reduction and performing meta-analysis. Results: The mean of bleeding reduction in aPCC and rFVIIa were 71.2% with CI 95% (lower limit 86.8% and upper limit 82%) and 72.3% with CI 95% (lower limit 57.6% and upper limit 83.4%), respectively. Conclusions: Although differences between the two products were very close to each other, they reported similar effects on joint bleeds. Further clinical studies should be performed by incorporating a standardized measurement in comparative efficacy of aPCC and rFVIIa.
2014
Context: Mild-to-moderate bleeding disorders in haemophilia are primarily treated via recombinant activated factor VII a (rFVIIa) or activated prothrombin complex concentrate (aPCC). However, the efficacy of each bypassing agents may vary and none of them is universally effective. Evidence Acquisition: After reviewing the databases of PubMed, Scopus, MD Consult, Ovid, Trip database, Google Scholar, ProQuest and the Cochrane Library, finally, 17 papers published from 2000 to 2013 were extracted. We used as a random effect model in meta-analysis. Comprehensive meta-analysis (CMA) software was used for calculating and estimating the mean of bleeding reduction and performing meta-analysis. Results: The mean of bleeding reduction in aPCC and rFVIIa were 71.2% with CI 95% (lower limit 86.8% and upper limit 82%) and 72.3% with CI 95% (lower limit 57.6% and upper limit 83.4%), respectively. Conclusions: Although differences between the two products were very close to each other, they reported similar effects on joint bleeds. Further clinical studies should be performed by incorporating a standardized measurement in comparative efficacy of aPCC and rFVIIa.
American journal of hematology, 2017
Self-administration of factor and bypassing agents by persons with hemophilia in the home setting is recommended to facilitate earlier intervention after bleeding episodes. The objective of this review was to summarize recombinant activated coagulation factor VII (rFVIIa) safety and efficacy data from clinical trials and patient registries documenting use in the home treatment setting in people with congenital hemophilia with inhibitors (CHwI). A total of 16 studies and registries were identified for inclusion; 14 evaluated on-demand treatment of acute bleeding episodes (865 patients, 9024 bleeding episodes) and 2 evaluated use for secondary prophylaxis (108 patients, 42,861 prophylaxis days). In the on-demand studies, efficacy was consistently high (81%-96%), and thrombotic events were uncommon (n=3). In the secondary prophylaxis studies, rFVIIa was associated with a 45% to 59% reduction in bleeding episodes and no thrombotic events. These data support the clinical practice of admi...