Experience with a single dose of recombinant activated factor VII for the management of mild-to-moderate bleeds in haemophilia

D, Almagro; Agramonte, Olga; Castillo, Dunia; Zamora, Yelka; Ballester, José Manuel

doi:10.1111/j.1365-2516.2010.02403.x

Cited by 3 publications

(4 citation statements)

References 5 publications

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“…Results from three randomised clinical trials in patients aged 1–50 years show that a single dose of 270 μg/kg is at least as efficacious and safe as three doses of 90 μg/kg each . In another study, a single dose of 150 μg/kg stopped mild‐to‐moderate bleeding in 37.5% of bleeding episodes in adults, with haemostasis being achieved in the remaining 62.5% of bleeding episodes after a second dose of 90 μg/kg . Data from the Haemophilia and Thrombosis Research Society (HTRS) Registry also showed significantly increased efficacy with doses above 200 μg/kg, compared with doses below 200 μg/kg (97% vs 84%; P < 0.001), suggesting that a single high‐dose injection is an alternative to repeat standard dosing .…”

Section: Resultsmentioning

confidence: 99%

“…[29][30][31] In another study, a single dose of 150 mg/kg stopped mild-to-moderate bleeding in 37.5% of bleeding episodes in adults, with haemostasis being achieved in the remaining 62.5% of bleeding episodes after a second dose of 90 mg/kg. 32 Data from the Haemophilia and Thrombosis Research Society (HTRS) Registry also showed significantly increased efficacy with doses above 200 mg/kg, compared with doses below 200 mg/kg (97% vs 84%; P < 0.001), suggesting that a single high-dose injection is an alternative to repeat standard dosing. 33 Evidence for the safety of higher doses was provided by an HTRS Registry data analysis of 172 bleeds in patients with a median age of 6.5 years (range: 0.4-41.7 years) treated with rFVIIa 250 mg/kg or higher, with no serious adverse drug-related events or thrombotic complications being reported.…”

Section: Aims Of Treatment With Rfviiamentioning

confidence: 99%

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How we use recombinant activated Factor VII in patients with haemophilia A or B complicated by inhibitors

Brown

Barnes

Curtin

et al. 2012

Internal Medicine Journal

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The management of bleeds in patients with haemophilia A or B complicated by inhibitors is complex. Recombinant activated Factor VII (rFVIIa; NovoSeven RT) is an established therapy in these patients. To develop a consensus-based guide on the practical usage of rFVIIa in haemophilia complicated by inhibitors, nine expert haemophilia specialists from Australia and New Zealand developed practice points on the usage of rFVIIa, based on their experience and supported by published data. Practice points were developed for 13 key topics: control of acute bleeding; prophylaxis; surgical prophylaxis; control of breakthrough bleeding during surgery or treatment of acute bleeds; paediatric use; use in elderly; intracranial haemorrhage; immune tolerance induction; difficult bleeds; clinical monitoring of therapy; laboratory monitoring of therapy; concomitant antifibrinolytic medication; practical dosing. Access to home therapy with rFVIIa is important in allowing patients to administer treatment early in bleed management. In adults, 90-120 μg/kg is the favoured starting dose in most settings. Initial dosing using 90-180 μg/kg is recommended for children due to the effect of age on the pharmacokinetics of rFVIIa. In the management of acute bleeds, 2-hourly dosing is appropriate until bleeding is controlled, with concomitant antifibrinolytic medication unless contraindicated. The practice points provide guidance on the usage of rFVIIa for all clinicians involved in the management of haemophilia complicated by inhibitors.

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Section: Resultsmentioning

confidence: 99%

Section: Aims Of Treatment With Rfviiamentioning

confidence: 99%

How we use recombinant activated Factor VII in patients with haemophilia A or B complicated by inhibitors

Brown

Barnes

Curtin

et al. 2012

Internal Medicine Journal

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“…We previously described the use of PPRHs as a silencing tool in both in vitro and in vivo approaches (de Almagro et al, 2009;Almagro et al, 2011;Rodriguez et al, 2013), by decreasing the expression of different targets. In this work we present evidence that PPRHs can also be used as a tool for gene repair.…”

Section: Discussionmentioning

confidence: 99%

“…We had previously described the design and usage of template-PPRHs that bind to the template DNA strand (de Almagro et al, 2009), and coding-PPRHs binding to the coding DNA strand (de Almagro et al, 2011), as a tool to decrease gene expression (Rodriguez et al, 2013) that shows high stability and low immunogenicity properties without the need for chemical modifications (Villalobos et al, 2014). In this work we explored a new application for PPRHs: the repair of point mutations, an ambitious gene therapy strategy.…”

Section: Introductionmentioning

confidence: 99%

Repair of Single-Point Mutations by Polypurine Reverse Hoogsteen Hairpins

Solé

Villalobos²,

Ciudad³

et al. 2014

Human Gene Therapy Methods

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Polypurine reverse Hoogsteen hairpins (PPRHs) are formed by two intramolecularly bound antiparallel homopurine domains linked by a five-thymidine loop. One of the homopurine strands binds with antiparallel orientation by Watson-Crick bonds to the polypyrimidine target sequence, forming a triplex. We had previously reported the ability of PPRHs to effectively bind dsDNA displacing the fourth strand away from the newly formed triplex. The main goal of this work was to explore the possibility of repairing a point mutation in mammalian cells using PPRHs as tools. These repair-PPRHs contain different combinations of extended sequences of DNA with the corrected nucleotide to repair the point mutation. As a model we used the dihydrofolate reductase gene. On the one hand, we demonstrate in vitro that PPRHs bind specifically to their polypyrimidine target sequence, opening the two strands of the dsDNA, and allowing the binding of a given repair oligonucleotide to the displaced strand of the DNA. Subsequently, we show at a cellular level (Chinese ovary hamster cells) that repair-PPRHs are able to correct a single-point mutation in a dihydrofolate reductase minigene bearing a nonsense mutation, both in an extrachromosomal location and when the mutated plasmid was stably transfected into the cells. Finally, this methodology was successfully applied to repair a single-point mutation at the endogenous locus, using the DA5 cell line with a deleted nucleotide in exon six of the dhfr gene.

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Emicizumab in hemophilia A with inhibitors: clinical and economic impact of its use in a Cuban patient

Castillo-Gonzàles

Sardiñas²,

Abraham³

et al. 2022

abtpn

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Introduction: The management of a patient with severe hemophilia A with inhibitors is a challenge for any healthcare professional. The present analysis shows the clinical and economic impact of the therapeutic approach in the most critical patient of the Cuban Hemophilia Cohort. Objective: To evaluate the economic and clinical impact of the implementation of Emicizumab therapy in the first Cuban patient. Case presentation: Adult patient who started to use recombinant activated factor VII episodically during adolescence when he was diagnosed with the presence of high-responding antibodies against factor VIII. During the years that he used this medication, he had recorded between 95 and 105 bleeds annually. In 2018, he presented with severe hemoperitoneum and was admitted to the intensive care unit with high doses of recombinant factor VII activated, multiple transfusions of packed red blood cells, and other care typical of a critically ill patient; his evolution was satisfactory. He started emicizumab prophylaxis 7 months after this event and is currently on Week 133 of treatment. He has not presented with further bleeding, nor has he reported adverse reactions to this treatment. The biannual cost savings for on-demand treatment and prophylaxis have been US $792,509.24. Conclusions: Emicizumab prophylaxis improved the patient’s quality of life and that of his family. From the perspective of the Cuban health system, the use of emicizumab in this clinical case was satisfactory and its experience will be analyzed in new patients.

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Experience with a single dose of recombinant activated factor VII for the management of mild-to-moderate bleeds in haemophilia

Cited by 3 publications

References 5 publications

How we use recombinant activated Factor VII in patients with haemophilia A or B complicated by inhibitors

How we use recombinant activated Factor VII in patients with haemophilia A or B complicated by inhibitors

Repair of Single-Point Mutations by Polypurine Reverse Hoogsteen Hairpins

Emicizumab in hemophilia A with inhibitors: clinical and economic impact of its use in a Cuban patient

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