Search results for "FVII"
showing 10 items of 13 documents
Recombinant factor VIII: past, present and future of treatment of hemophilia A.
2018
The development of recombinant factor VIII (rFVIII) was initially driven by the necessity to treat hemophilia A (HA) patients with FVIII concentrates without the risk of transmitting infectious agents. Over the last three decades the safety of rFVIII has been further improved by completely removing animal or human proteins from the manufacturing process, so that patients would not be exposed to known or emerging pathogens. Recent efforts have concentrated on improving the expression of rFVIII, reducing its immunogenicity and enhancing its pharmacokinetic (PK) behavior. These new goals have been possible thanks to the develop-ment of biotechnology and a better knowledge of the function and s…
The important impact of dental care on haemostatic treatment burden in patients with mild haemophilia
2022
Background: Mild haemophilia (MH) is mainly characterized by haemorrhages secondary to surgery/invasive procedures or trauma. Haemostatic treatment in MH ranges from on demand to short prophylaxis according to the type of bleeding events and the basal clotting factor level. Oral surgery and dental extractions can represent a frequent haemostatic challenge in MH requiring appropriate treatment. However, only few studies on limited numbers of patients are available in the literature regarding the implications of dental management in patients with MH. Objectives: The purpose of the study was to evaluate the impact of dental care on the burden of haemostatic treatment in patients affected by MH…
Thrombosis in inherited factor VII deficiency
2003
Thrombosis in congenital factor (F) VII deficiency was investigated through extensive phenotypic and molecular-genetic studies. Patients with a history of thrombosis among 514 entries in the FVII Deficiency Study Group database were evaluated. Thrombotic events were arterial in one case, disseminated intravascular coagulation in another and venous in seven. Gene mutations were characterized in eight patients: three were homozygous, three compound heterozygous and two heterozygous. FXa and IIa generation assays were consistent with the genetic lesions. One patient was heterozygous for the FV Leiden and one for the FIIG20210A mutation. In seven patients, surgical interventions and/or replacem…
Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study
2015
Background: Elevated levels of FVIII:c are associated with risk for both venous and arterial thromboembolism. However, no population-based study on the sex-specific distribution and reference ranges of plasma FVIII: c and its cardiovascular determinants is available. Methods: FVIII:c was analyzed in a randomly selected sample of 2533 males and 2440 females from the Gutenberg Health Study in Germany. Multivariable regression analyses for FVIII:c were performed under adjustment for genetic determinants, cardiovascular risk factors and cardiovascular disease. Results and conclusions: Females (126.6% (95% CI: 125.2/128)) showed higher FVIII:c levels than males (121.2% (119.8/122.7)). FVIII:c le…
Tailoring haemophilia A prophylaxis with BAY 81-8973: A case series
2020
BAY 81-8973 is an unmodified, full-length third generation recombinant factor VIII (rFVIII) which offers a more favorable pharmacokinetic (PK) profile, compared to its predecessor sucrose-formulated rFVIII (rFVIII-FS). We here report on a retrospective case series of nine patients affected by hemophilia A (HA), with variable disease severity, bleeding phenotype and comorbidities, to underline our clinical practice on prophylaxis with a recently introduced standard hall-life recombinant Factor VIII. The current case series highlights how the current clinical management of hemophilia is able to personalize treatment in several specific conditions like concomitant illnesses with thrombotic ris…
Can we compare haemophilia carriers with clotting factor deficiency to male patients with mild haemophilia?
2020
Introduction Certain haemophilia carriers demonstrate an increased bleeding tendency, mainly related to clotting factor deficiency. No study has so far formally compared the bleeding phenotype of women and girls with mild FVIII or FIX deficiency and associated management with that of male patients affected by mild haemophilia A and B. Material and methods We retrospectively evaluated 44 women and girls with mild FVIII or FIX deficiency (FVIII or FIX 0.05-0.5 IU/mL) and 77 male patients with mild haemophilia A or B and compared them with respect to clotting factor level, age at and trigger for diagnosis, as well as treatment modalities. Results After excluding gender-related haemorrhagic sym…
Emergency management in patients with haemophilia A and inhibitors on prophylaxis with emicizumab: AICE practical guidance in collaboration with SIBi…
2020
Emicizumab has been approved in several countries for regular prophylaxis in patients with congenital haemophilia A and FVIII inhibitors because it substantially reduces their bleeding risk and improves quality of life. However, although significantly less frequent, some breakthrough bleeds may still occur while on emicizumab, requiring treatment with bypassing or other haemostatic agents. Thrombotic complications have been reported with the associated use of activated prothrombin complex concentrates. In addition, when surgery/invasive procedures are needed while on emicizumab, their management requires multidisciplinary competences and direct supervision by experts in the use of this agen…
Pharmacokinetic properties of recombinant FVIIa in inherited FVII deficiency account for a large volume of distribution at steady state and a prolong…
2014
Pharmacokinetic properties of recombinant FVIIa in inherited FVII deficiency account for a large volume of distribution at steady state and a prolonged pharmacodynamic effect -
Natural and engineered carboxy-terminal variants: decreased secretion and gain-of-function result in asymptomatic coagulation factor VII deficiency.
2012
We report 2 asymptomatic homozygotes for the nonsense p.R462X mutation affecting the carboxy-terminus of coagulation factor VII (FVII, 466 aminoacids). FVII levels of 3-5% and 2.7 ± 0.4% were found in prothrombin time-based and activated factor X (FXa) generation assays with human thromboplastins. Noticeably, FVII antigen levels were barely detectable (0.7 ± 0.2%) which suggested a gain-of-function effect. This effect was more pronounced with bovine thromboplastin (4.8 ± 0.9%) and disappeared with rabbit thromboplastin (0.7 ± 0.2%). This suggests that the mutation influences tissue factor/FVII interactions. Whereas the recombinant rFVII-462X variant confirmed an increase in specific activit…
Status of Recombinant Factor VIII Concentrate Treatment for Hemophilia A in Italy: Characteristics and Clinical Benefits
2019
The current interest in recombinant factor VIII (rFVIII) products stems from the fact that they offer a technological solution to prolonging the half-life of and reducing the risk of formation of alloantibodies (inhibitors) against FVIII in treated patients with hemophilia A (HA). The Italian health care system has authorized the use of a wide range of rFVIII concentrates of the first, second, and third generation, as well as new innovative rFVIII preparates with an extended half-life (EHL) (Kogenate FS®-Bayer, belonging to the second generation and replaced since 2017 by a product consisting of the same modified molecule; because it is only available until the end of the current year, it w…