Recombinant activated factor VII for a patient with factor VII deficiency undergoing urgent intracerebral haematoma evacuation with underlying cavernous angioma

Liu, N.; Aldéa, Sorin; François, Dominique; Cherqui-Michel, M.; Giansily‐Blaizot, Muriel; Fischler, Marc

doi:10.1093/bja/aep293

Cited by 8 publications

(5 citation statements)

References 14 publications

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“…A large number of different F7 gene variants, including missense, nonsense, promoter and splice site mutations, have been reported. In addition, the functional impact of certain variants has been investigated in order to provide evidence for the underlying molecular mechanisms of FVII deficiency (8,9).…”

Section: Introductionmentioning

confidence: 99%

Inï¿½vitro expression of mutant factor VII proteins and characterization of their clinical significance

et al. 2017

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Factor VII (FVII) serves an essential role in the initiation of blood coagulation. Mutations in conserved residues within its serine protease domain may lead to dysregulated coagulation activity. The objective of the present study was to elucidate the impact of altering two conserved residues, H348R and S282R, on the functional properties of the FVII protein. The mutation‑harboring fragments were derived from genomic DNA of a FVII deficient patient. The fragments were integrated into a pcDNA vector containing FVII cDNA of HepG2 cells. The wild-type and mutated FVII constructs were transfected into CHO‑K1 cells as a mammalian cell model. The coagulation activity, antigen levels and intracellular localization of the recombinant proteins were studied in association with their pathological importance. Results indicated that FVII activity was not detectable in conditioned media of the cells transfected with the mutated constructs. The H348R mutation reduced the expression of intracellular and secreted forms of the FVII protein. Following S282R transfection, intracellular FVII expression showed no significant variation; however, extracellular protein was reduced. The pattern of intracellular localization of mutated FVII remained unaltered in comparison to the wild-type protein. In conclusion, the present study suggested that missense mutations within the serine protease domain of FVII affect extracellular levels in addition to the coagulation activity of FVII. These results may contribute to further understanding of the molecular pathogenesis of FVII deficiency and the development of pharmaceutical candidates with improved therapeutic properties.

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Section: Introductionmentioning

confidence: 99%

Inï¿½vitro expression of mutant factor VII proteins and characterization of their clinical significance

et al. 2017

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“…In addition, in a study by Diprose et al [16] assessing the effect of activated recombinant factor VII in non coronary cardiac surgery and the need of transfusion after the cardiopulmonary bypass, the authors concluded that administrating recombinant factor VII was beneficial and reduced the need for blood transfusion in such patients without causing any side effects. Moreover, Liu and colleagues [17] studied the value of recombinant factor VII in patients for intracerebral hematoma drainage having factor VII deficiency and found out that its use was effective in emergency neurosurgery. On the contrary, in a study by Bowels and colleagues [18] for predicting the response of non-hemophilic patients with bleeding to activated recombinant factor VII, they showed that only eight patients responded to an early single dose of factor VII who had good prognosis while patients with poor prognosis showed no response suggesting that its efficacy depending on the time of administration that may affect the prognosis.…”

Section: Discussionmentioning

confidence: 99%

Effect of activated recombinant factor VII versus tranexamic acid infusion on bleeding during spine surgery, randomized, controlled, double blinded trial

ELShamaa

Elokda

2015

Egyptian Journal of Anaesthesia

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Background: Antifibrinolytic drugs, such as tranexamic acid are medications that facilitate hemostasis and decrease blood loss and the need for blood transfusion during major surgery. Activated recombinant coagulation factor VII is a novel hemostatic agent, studies revealed that it is helpful hemostatic in disorders with impaired hemostasis, as well as in patients with normal hemostatic function to minimize perioperative blood loss. This study aimed to compare the efficacy of activated recombinant factor VII with tranexamic acid in reducing the perioperative blood loss. Methods: 50 patients undergoing spine surgery were enrolled in this study. Group A patients were given activated recombinant factor VII and group T patients given tranexamic acid. In both groups, anesthesia was induced using fentanyl 3 lg/kg and propofol 2 mg/kg; muscle relaxation was initiated using cisatracurium 0.2 mg/kg. Transfusion of blood and its products was done according to a value guide. The primary outcome variable of the study was the total volume of blood loss in the perioperative period. Secondary outcome variables include perioperative transfusion requirement, and the number of patients who needed transfusion, as well as time of operation. A P-value less than 0.05 is considered statistically significant. Results: The current study showed that the total perioperative blood loss in group A was significantly lower than group T. None of the patients required ICU admission, as well as reentry to operating theater. Furthermore, no significant difference was detected in the number of patients needed blood transfusion. Intraoperative bleeding was associated with a slight decrease of hemoglobin in group A. Conclusion: The present study concluded that administration of activated recombinant factor VII in spine surgery reduces the total perioperative blood loss and the total volume of intraoperative blood transfusion compared with tranexamic acid, with no evidence of adverse effects.

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“…In the past, plasma-based therapies such as fresh frozen plasma, plasma-derived FVII concentrates or prothrombin complex concentrates were the available treatment options for patients with FVII deficiency [10]. Currently, the most commonly administered treatment option is recombinant activated FVII (rFVIIa) (NovoSeven1, Novo Nordisk A/S, Bagsvaerd, Denmark) [6], which is indicated in Japan for the treatment of bleeding and for the prevention of bleeding during surgery/invasive procedures in patients with congenital FVII deficiency [11].…”

Section: Introductionmentioning

confidence: 99%

A multicenter, observational study to evaluate hemostasis following recombinant activated FVII treatment in patients in Japan with congenital factor VII deficiency

Seita

Kinai

2023

Blood Coagulation &Amp; Fibrinolysis

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Reports describing symptoms and treatment of patients with congenital factor VII (FVII) deficiency frequently relate to patients in Europe, while only a small number describe data from Asian countries. This multicenter, prospective observational study (NCT01312636) collected data from 30 sites for 55% of patients registered in 2011 in Japan with congenital FVII deficiency treated with activated recombinant FVII (rFVIIa) for bleeding episodes and/or during surgery. The mean follow-up in 20 eligible patients was 11 months (range 1–49 months). Of 348 bleeding episodes in seven patients, 170 (48.9%) were intra-articular bleeding and 62 (17.8%) were menorrhagia, of which 92.9% (158/170) and 100% (62/62) were in patients with baseline factor VII activity 20 IU/dl or less, respectively. The hemostatic effect after rFVIIa treatment was rated as excellent, effective or partially effective for 45.7, 33.6 and 18.4% of 348 bleeding episodes. Overall, hemostasis for bleeding events and surgery was achieved in nearly 2 days, with the majority of patients receiving two doses or less. The hemostatic effect after the recommended dose (15–30 μg/kg) of rFVIIa was rapid and effective treatment for all categories of bleeding and surgical procedure. On the basis of data from routine clinical practice, no new safety signals were identified. Trial Registration NCT01312636

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Recombinant activated factor VII for a patient with factor VII deficiency undergoing urgent intracerebral haematoma evacuation with underlying cavernous angioma

Cited by 8 publications

References 14 publications

Inï¿½vitro expression of mutant factor VII proteins and characterization of their clinical significance

Inï¿½vitro expression of mutant factor VII proteins and characterization of their clinical significance

Effect of activated recombinant factor VII versus tranexamic acid infusion on bleeding during spine surgery, randomized, controlled, double blinded trial

A multicenter, observational study to evaluate hemostasis following recombinant activated FVII treatment in patients in Japan with congenital factor VII deficiency

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