scholarly journals Implantoprosthetic rehabilitation of a patient with severe form of hemophilia B: a case report

2018 ◽  
Vol 49 (1) ◽  
pp. 33-36
Author(s):  
Aneta Neskoromna-Jędrzejczak ◽  
Katarzyna Bogusiak ◽  
Krzysztof Chojnowski ◽  
Marta Robak ◽  
Jacek Treliński
Keyword(s):  
Coagulation Factor ◽  
Severe Form ◽  
Factor Ix ◽  
Hemophilia B ◽  
Severe Hemophilia ◽  
Dental Implantation ◽  
Dental Procedures ◽  
Recombinant Factor Ix ◽  
Hemostatic Therapy ◽  
Surgical Operations

AbstractThe preparation of patients with hemophilia before surgical operations and dental procedures constitutes a significant clinical challenge. This article presents the implantoprosthetic rehabilitation of a patient with severe hemophilia B (factor IX activity <1%). The patient was prepared for the surgical procedure with recombinant factor IX concentrate (Rixubis) during the clinical surgery study. Tooth extraction and the implantation of four dental implants in the mandible were planned: one dental implant of 3.7 mm diameter and 10 mm length in the place of tooth 35, and another of 3.2 mm diameter and 10 mm length in the place of tooth 37. The next two implants were implemented 1 month later: one implant 3.7 mm in diameter and 10 mm in length in the place of tooth 46, and another implant 3.2 mm in diameter and 10 mm in length in the area of tooth 44. Appropriate substitution of the missing coagulation factor, together with the use of local hemostatic therapy, allowed dental implantation to be performed without excessive blood loss in this patient with severe hemophilia B.

Biochemical Characterization of a Recombinant FIX Drug Candidate for Treatment of Hemophilia B

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4658-4658
Author(s):  
Peter Turecek ◽  
Susanne Vejda ◽  
Katalin Varadi ◽  
Hanspeter Rottensteiner ◽  
Ernst Boehm ◽  
...  
Keyword(s):  
Biochemical Characterization ◽  
Drug Product ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Hemophilia B ◽  
Drug Candidate ◽  
Alternative Drug ◽  
Recombinant Factor Ix ◽  
Fermentation Technology

Abstract Abstract 4658 Human coagulation factor IX (FIX) is a vitamin-K-dependent coagulation factor whose absence or dysfunction causes hemophilia B. Treatment of hemophilia B is based on replacement therapy using highly purified FIX concentrates. Baxter has developed a recombinant factor IX for treating hemophilia B patients that is produced in a CHO cell-line using a serum and protein-free fermentation technology. The purification process avoids the use of immune-affinity chromatography and includes two viral reduction steps. The final drug product is formulated in the absence of proteins of animal or human origin. Baxter's recombinant FIX resembles commercially available rFIX in most characteristics with the exception of a significantly lower FIXa content, which might improve standardization compared to commercial rFIX products. Preclinical and clinical lots of rFIX were characterized with respect to their hemostatic potency, efficiency of activation by FXIa and FVIIa in the presence of tissue factor, and capacity to bind to phospholipid vesicles. Three lots of commercial rFIX with different potencies and one lot of a plasma-derived FIX product were included in the study. Similarity could be shown between the preclinical and clinical lots of rFIX in all these assays. Furthermore, the functional and biochemical characterization of Baxter's recombinant FIX showed that it resembles the recombinant comparator product. The phase I clinical trial which has been initiated will now have to show whether Baxter's rFIX can become an alternative drug candidate product for treating patients suffering from hemophilia B. Disclosures: Turecek: Baxter Innovations GmbH: Employment. Vejda:Baxter Innovations GmbH: Employment. Varadi:Baxter Innovations GmbH: Employment. Rottensteiner:Baxter Innovations GmbH: Employment. Boehm:Baxter Innovations GmbH: Employment. Reiter:Baxter Innovations GmbH: Employment. Kaliwoda:Baxter Innovations GmbH: Employment. Mundt:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment.

scholarly journals Phase 3 Clinical Trial: Perioperative Use of Nonacog Gamma, a Recombinant Factor IX, in Previously Treated Patients With Moderate/Severe Hemophilia B

2020 ◽  
Vol 26 ◽  
pp. 107602962094683
Author(s):  
Jerzy Windyga ◽  
Margarita Timofeeva ◽  
Oleksandra Stasyshyn ◽  
Vasily Mamonov ◽  
José Luis Lamas Castellanos ◽  
...  
Keyword(s):  
Elective Surgery ◽  
Study Drug ◽  
Factor Ix ◽  
Hemophilia B ◽  
Severe Hemophilia ◽  
Phase 3 ◽  
Recombinant Factor Ix ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Hemostatic Efficacy

Hemostatic management is essential for ensuring the safety of patients with hemophilia during surgery. This phase 3, prospective, uncontrolled trial, evaluated hemostatic efficacy, consumption, and safety of a recombinant factor IX concentrate, nonacog gamma (BAX 326, Rixubis® [Baxalta US Inc., a Takeda company, Lexington, MA, USA]), in intraoperative and postoperative settings in previously treated patients (PTPs) with severe or moderately severe hemophilia B undergoing elective surgery (N = 38 surgeries; 21 major, 17 minor). Predefined preoperative hemostatic factor IX levels (80-100% of normal for major and 30-60% for minor surgeries) were maintained for each patient. Intraoperative efficacy was rated as “excellent” or “good” for all surgeries. Postoperative hemostatic efficacy on day of discharge was rated as “excellent,” “good,” and “fair,” respectively, for 29 (76.3%), 7 (18.4%), and 2 (5.3%) surgical procedures. All adverse events were considered unrelated to study drug; most frequently reported was mild procedural pain (9 patients). No thrombotic events, severe allergic reactions, or inhibitor formation were observed. Nonacog gamma was well tolerated and effective for intraoperative and postoperative hemostatic management of PTPs with hemophilia B. NCT01507896, EudraCT: 2011-000413-39

SVA retrotransposition in exon 6 of the coagulation factor IX gene causing severe hemophilia B

2015 ◽  
Vol 102 (1) ◽  
pp. 134-139 ◽  
Author(s):  
Yuki Nakamura ◽  
Moe Murata ◽  
Yuki Takagi ◽  
Toshihiro Kozuka ◽  
Yukiko Nakata ◽  
...  
Keyword(s):  
Coagulation Factor ◽  
Factor Ix ◽  
Hemophilia B ◽  
Severe Hemophilia ◽  
Coagulation Factor Ix

Hemostatic Management in an Infant With Neuroblastoma and Severe Hemophilia B With Extended Half-life Recombinant Factor IX Fusion Protein

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Franziska Cuntz ◽  
Hedwig E. Deubzer ◽  
Johannes H. Schulte ◽  
Antje Nimtz-Talaska ◽  
Angelika Eggert ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Half Life ◽  
Factor Ix ◽  
Hemophilia B ◽  
Severe Hemophilia ◽  
Recombinant Factor Ix

Pharmacokinetic/Pharmacodynamic Assessment of Reformulated Recombinant Coagulation Factor IX in Adults and Children with Severe Hemophilia B

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1190-1190
Author(s):  
JM Korth-Bradley ◽  
Leonard A. Valentino ◽  
Pablo Rendo ◽  
Frank E. Shafer ◽  
Lynne Smith ◽  
...  
Keyword(s):  
Medical Center ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Hemophilia B ◽  
Pharmacokinetic Data ◽  
Severe Hemophilia ◽  
Bleeding Events ◽  
On Demand ◽  
Coagulation Factor Ix ◽  
Weekly Group

Abstract Abstract 1190 Introduction: The goal of this study was to evaluate the efficacy and safety of two prophylaxis regimens of reformulated recombinant coagulation factor IX (rFIX-R), 100 IU/kg once weekly and 50 IU/kg twice weekly, compared with on-demand treatment in subjects with severe hemophilia B. Patients and Methods: Pharmacokinetic data were collected for 47 subjects aged 6 to 64 years with severe hemophilia B. Factor IX activity (FIX:C) measurements were made immediately before rFIX-R administration and at 0.5 hours post-administration of either 100 IU/kg or 50 IU/kg doses, to assess recovery before the initiation of each weekly regimen. Another FIX:C sample was collected at least 72 hours after dosing during each regimen. All samples were analyzed at local laboratories. Results: The mean prophylactic doses of rFIX-R administered were 86 ± 29 IU/kg in the 100 IU/kg once-weekly group and 53 ± 14 IU/kg in the 50 IU/kg twice-weekly group. The treatment comparison between the two prophylaxis regimens for annualized bleeding rate was not significant (LS mean = 2.0; 95% CI, −1.2 – 5.2; n=43), although both were significantly different from the on-demand treatment period (both, P<.0001). The number of new bleeding events in each group was 51 and 35, respectively, with only 12/51 new hemorrhages occurring within 72 hours of dosing in the 100 IU/kg once-weekly group compared with 29/35 in the 50 IU/kg twice-weekly group. The pharmacokinetic results are shown in the Table. The number (%) of observed trough plasma concentrations (Ctrough) that fell into the mild (>5%) range for hemophilia were 18 (45%) and 19 (48%) for the r-FIX-R 100 IU/kg once-weekly and 50 IU/kg twice-weekly groups, respectively. However, the severe phenotype was observed in 4 (10%) and 3 (7%) subjects, respectively. Conclusions: The pharmacokinetics of r-FIX-R are dose proportional. The C0.5hr increased in proportion to the dose administered. Recovery was consistent between the two prophylaxis regimens. Both regimens provided similar therapeutic results for Ctrough. The apparent difference in time after dose of new bleeding events between the 2 regimens is intriguing and deserves further study. Disclosures: Korth-Bradley: Pfizer Inc: Employment. Valentino:Inspiration Bioscience: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; CSL Behring: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center; Pfizer: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center; NovoNordisk: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; GTC Biotherapeutics: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; Bayer Healthcare: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; Baxter Bioscience: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; Biogen: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center; Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees, Past-President. Rendo:Pfizer Inc: Employment. Shafer:Pfizer Inc: Employment. Smith:Pfizer Inc: Employment. Baumann:Pfizer Inc: Employment. Charnigo:Pfizer Inc: Employment.

The novel mutation p.Asp315Tyr causes severe hemophilia B by impairing coagulation factor IX expression

2021 ◽  
Vol 198 ◽  
pp. 23-25
Author(s):  
Zhengjing Lu ◽  
Huayang Zhang ◽  
Changming Chen ◽  
Wenman Wu ◽  
Hongying Wei
Keyword(s):  
Novel Mutation ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Hemophilia B ◽  
The Novel ◽  
Severe Hemophilia ◽  
Coagulation Factor Ix

Adeno-Associated Virus-Mediated Gene Transfer of Factor IX for Treatment of Hemophilia B by Gene Therapy

1999 ◽  
Vol 82 (08) ◽  
pp. 540-546 ◽  
Author(s):  
Roland Herzog ◽  
Katherine High
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Biologically Active ◽  
Hemophilia B ◽  
Clotting Factor ◽  
Severe Hemophilia ◽  
Dog Model ◽  
Life Threatening

IntroductionPatients with severe hemophilia have circulating blood coagulation factor VIII (hemophilia A) or factor IX (hemophilia B) levels below 1% of normal due to a genetic defect in the respective X-linked gene. The resulting bleeding disorder is characterized by spontaneous joint bleeds or, in a more life-threatening situation, into critical closed spaces, such as the intracranial or retroperitoneal space. Current treatment for hemophilia is based on intravenous infusions of clotting factor concentrates. These can be episode-based in response to bleeds (which does not prevent ongoing tissue damage nor the risk of a life-threatening bleed) or prophylactic (an expensive and not always practical alternative). The goal of a gene-based therapy is to introduce a functional clotting factor gene into a patient in order to provide a continuous supply of factor levels above 1%.1,2 Clinical endpoints for the efficacy of potential gene therapy trials for hemophilia are, therefore, well-defined and unequivocal.The relatively small size of the factor IX coding sequence (1.4 kb) and the fact that a number of cell types other than hepatocytes (which normally synthesize factor IX) are capable of producing biologically-active factor IX have contributed to the development of hemophilia B into an important model for the treatment of genetic diseases by gene therapy. The factor IX gene can be incorporated into a variety of vector systems. Various target tissues can be chosen for gene transfer as long as the secreted factor IX reaches the circulation and tight regulation of transgene expression is not required.3 Possibly most important in research on gene therapy for coagulation factor deficiencies, and genetic disorders in general, is the availability of a large animal model with severe disease. In this case, it is the well-characterized hemophilia B dogs maintained at the University of North Carolina at Chapel Hill. The animals contain a point-mutation in the portion of the factor IX gene encoding the catalytic domain. This mutation results in an absence of circulating factor IX antigen and, consequently, severe hemophilia B that closely mimics the human disease.4 Gene therapy strategies for hemophilia B have typically established a method of gene transfer, resulting in expression of factor IX in mice, and subsequently, attempted scale-up to the dog model. These investigations have established experiments in the hemophilic dog model as a critical step for the assessment of the efficacy of gene therapy protocols showing initial promise in mice. For example, reimplantation of primary myoblasts that had been transduced ex vivo with a retrovirus was successful in mice, but not in the canine model.5 Adenoviral gene transfer, characterized by varying success in mice, depending on the strain and dose used, has persistently resulted in high, but transient expression following intravenous infusion into dogs.6,7 Cellular immune responses and hepatotoxicity have limited the expression of factor IX from adenoviral vectors to just a few weeks. Repeat administration of the vector was complicated by the induction of neutralizing antibodies to viral particles in injected animals following the first administration. Retroviral gene transfer to hepatocytes was successful in long-term expression of factor IX in hemophilia B dogs but required a partial hepatectomy prior to infusion of the vector through the portal vein. The resulting expression levels were no higher than 0.1% of normal human factor IX levels.8

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