hemophilia a

Summary

Summary: The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage.

Top Publications

  1. ncbi Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia
    Marilyn J Manco-Johnson
    University of Colorado and Health Sciences Center, Denver, USA
    N Engl J Med 357:535-44. 2007
  2. ncbi F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis
    Samantha C Gouw
    Department of Pediatrics, Wilhelmina Children s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
    Blood 119:2922-34. 2012
  3. pmc Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients
    Jerry S Powell
    University of California, Davis, Sacramento, CA, USA
    Blood 119:3031-7. 2012
  4. pmc Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs
    Jennifer A Dumont
    Research and Development, Biogen Idec Hemophilia, Waltham, MA 02451, USA
    Blood 119:3024-30. 2012
  5. ncbi Factor VIII products and inhibitor development in severe hemophilia A
    Samantha C Gouw
    Department of Pediatrics, Wilhelmina Children s Hospital, Utrecht, The Netherlands
    N Engl J Med 368:231-9. 2013
  6. ncbi Modern haemophilia care
    Erik Berntorp
    Lund University, Malmö Centre for Thrombosis and Haemostasis, Skane University Hospital, Malmo, Sweden
    Lancet 379:1447-56. 2012
  7. ncbi Improvements in factor concentrates
    David Lillicrap
    Department of Pathology and Molecular Medicine, Richardson Laboratory, Queen s University, Kingston, Canada
    Curr Opin Hematol 17:393-7. 2010
  8. pmc Directed engineering of a high-expression chimeric transgene as a strategy for gene therapy of hemophilia A
    Christopher B Doering
    Aflac Cancer Center and Blood Disorders Service, Department of Pediatrics, Emory University, Atlanta, Georgia 30322, USA
    Mol Ther 17:1145-54. 2009
  9. pmc A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A
    Jerome Lane
    School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
    Hum Mol Genet 22:1903-10. 2013
  10. ncbi The epidemiology of inhibitors in haemophilia A: a systematic review
    J Wight
    ScHARR, University of Sheffield, Sheffield, S1 4DA, UK
    Haemophilia 9:418-35. 2003

Detail Information

Publications379 found, 100 shown here

  1. ncbi Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia
    Marilyn J Manco-Johnson
    University of Colorado and Health Sciences Center, Denver, USA
    N Engl J Med 357:535-44. 2007
    ..Effective ways to prevent arthropathy in severe hemophilia are unknown...
  2. ncbi F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis
    Samantha C Gouw
    Department of Pediatrics, Wilhelmina Children s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
    Blood 119:2922-34. 2012
    ..effect estimates of inhibitor development for the various types of F8 gene mutations in patients with severe hemophilia A. The primary outcome was inhibitor development and the secondary outcome was high-titer-inhibitor development...
  3. pmc Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients
    Jerry S Powell
    University of California, Davis, Sacramento, CA, USA
    Blood 119:3031-7. 2012
    ..of ∼ 8-12 hours, requiring frequent intravenous injections for prophylaxis and treatment of patients with hemophilia A. rFVIIIFc is a recombinant fusion protein composed of a single molecule of FVIII covalently linked to the Fc ..
  4. pmc Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs
    Jennifer A Dumont
    Research and Development, Biogen Idec Hemophilia, Waltham, MA 02451, USA
    Blood 119:3024-30. 2012
    Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII...
  5. ncbi Factor VIII products and inhibitor development in severe hemophilia A
    Samantha C Gouw
    Department of Pediatrics, Wilhelmina Children s Hospital, Utrecht, The Netherlands
    N Engl J Med 368:231-9. 2013
    For previously untreated children with severe hemophilia A, it is unclear whether the type of factor VIII product administered and switching among products are associated with the development of clinically relevant inhibitory antibodies (..
  6. ncbi Modern haemophilia care
    Erik Berntorp
    Lund University, Malmö Centre for Thrombosis and Haemostasis, Skane University Hospital, Malmo, Sweden
    Lancet 379:1447-56. 2012
    ..Development of new products with improved pharmacokinetics is the next step to improved therapy...
  7. ncbi Improvements in factor concentrates
    David Lillicrap
    Department of Pathology and Molecular Medicine, Richardson Laboratory, Queen s University, Kingston, Canada
    Curr Opin Hematol 17:393-7. 2010
    ..During the past 5 years, significant progress has been made with a variety of protein-engineering initiatives, some of which are already in early-phase clinical trials...
  8. pmc Directed engineering of a high-expression chimeric transgene as a strategy for gene therapy of hemophilia A
    Christopher B Doering
    Aflac Cancer Center and Blood Disorders Service, Department of Pediatrics, Emory University, Atlanta, Georgia 30322, USA
    Mol Ther 17:1145-54. 2009
    ..to human fVIII and was delivered by lentiviral vectors (LVs) to hematopoietic stem cells for gene therapy of hemophilia A. Recombinant human immunodeficiency virus-based vectors encoding the fVIII chimera efficiently transduced human ..
  9. pmc A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A
    Jerome Lane
    School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
    Hum Mol Genet 22:1903-10. 2013
    ..Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (..
  10. ncbi The epidemiology of inhibitors in haemophilia A: a systematic review
    J Wight
    ScHARR, University of Sheffield, Sheffield, S1 4DA, UK
    Haemophilia 9:418-35. 2003
    ....
  11. ncbi A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model
    Takehisa Kitazawa
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical, Gotemba, Shizuoka, Japan
    Nat Med 18:1570-4. 2012
    b>Hemophilia A is a bleeding disorder resulting from coagulation factor VIII (FVIII) deficiency. Exogenously provided FVIII effectively reduces bleeding complications in patients with severe hemophilia A...
  12. ncbi Mechanism and kinetics of factor VIII inactivation: study with an IgG4 monoclonal antibody derived from a hemophilia A patient with inhibitor
    M G Jacquemin
    Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium
    Blood 92:496-506. 1998
    The development of an immune response towards factor VIII (fVIII) remains a major complication for hemophilia A patients receiving fVIII infusions...
  13. pmc Phenotypic correction of murine hemophilia A using an iPS cell-based therapy
    Dan Xu
    Division of Laboratory Medicine, Nevada Cancer Institute, Las Vegas, NV 89135, USA
    Proc Natl Acad Sci U S A 106:808-13. 2009
    b>Hemophilia A is caused by mutations within the Factor VIII (FVIII) gene that lead to depleted protein production and inefficient blood clotting. Several attempts at gene therapy have failed for various reasons-including immune rejection...
  14. ncbi Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia
    A Peden
    National Creutzfeldt Jakob Disease Surveillance Unit, University of Edinburgh, Edinburgh, UK
    Haemophilia 16:296-304. 2010
    ....
  15. ncbi Social participation of patients with hemophilia in the Netherlands
    Iris Plug
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
    Blood 111:1811-5. 2008
    ..After the introduction of prophylactic treatment, the number of patients who are occupationally disabled is reduced...
  16. pmc Long-term expression of human coagulation factor VIII in a tolerant mouse model using the φC31 integrase system
    Christopher L Chavez
    Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305 5120, USA
    Hum Gene Ther 23:390-8. 2012
    We generated a mouse model for hemophilia A that combines a homozygous knockout for murine factor VIII (FVIII) and a homozygous addition of a mutant human FVIII (hFVIII)...
  17. ncbi Prophylaxis for severe haemophilia: clinical and economical issues
    K Fischer
    Department of Paediatrics, University Medical Center Utrecht, The Netherlands
    Haemophilia 9:376-81. 2003
    ..In young adults, the cost of intermediate dose prophylaxis is similar, but outcome is better than for on demand treatment. The cost of high dose prophylaxis is twofold higher, further improving outcome only slightly...
  18. ncbi A study of variations in the reported haemophilia A prevalence around the world
    J S Stonebraker
    College of Management, North Carolina State University, Raleigh, NC 27695 7229, USA
    Haemophilia 16:20-32. 2010
    ..In addition, this information can help manufacturers plan the production of concentrates and prevent future shortages...
  19. ncbi A flow cytometry evaluation of anti-FVIII antibodies: correlation with ELISA and Bethesda assay
    M B Irigoyen
    Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
    Haemophilia 17:267-74. 2011
    ..This test provides a useful alternative for measuring FVIII antibodies supplementing Bethesda assay. FC is fast and easy to perform. No more than 200 μL of plasma or serum is required especially making it useful for paediatric patients...
  20. ncbi Identification of factor VIII gene mutations in 101 patients with haemophilia A: mutation analysis by inversion screening and multiplex PCR and CSGE and molecular modelling of 10 novel missense substitutions
    G Jayandharan
    Department of Hematology, Christian Medical College, Vellore, India
    Haemophilia 11:481-91. 2005
    ..The data from this study suggests that the spectrum of gene defects in Indian patients with HA is as heterogeneous as reported in other populations...
  21. pmc Efficacy and safety of long-term prophylaxis in severe hemophilia A dogs following liver gene therapy using AAV vectors
    Denise E Sabatino
    Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 19:442-9. 2011
    Developing adeno-associated viral (AAV)-mediated gene therapy for hemophilia A (HA) has been challenging due to the large size of the factor VIII (FVIII) complementary DNA and the concern for the development of inhibitory antibodies to ..
  22. ncbi The prevalence of proteolytic antibodies against factor VIII in hemophilia A
    Sebastien Lacroix-Desmazes
    INSERM Unité 430 and Université Pierre et Marie Curie, Hopital Broussais, Paris, France
    N Engl J Med 346:662-7. 2002
    ..are IgG alloantibodies that arise during replacement therapy in 25 to 50 percent of patients with severe hemophilia A. The hydrolysis of factor VIII by anti--factor VIII antibodies has been proposed as a mechanism of inactivation ..
  23. ncbi Quality-of-life differences between prophylactic and on-demand factor replacement therapy in European haemophilia patients
    S Royal
    Research Triangle Institute, Washington, USA
    Haemophilia 8:44-50. 2002
    ..While these results suggest that health-related quality-of-life may be better for haemophilia patients treated prophylactically, future prospective studies that gather periodic quality-of-life data over time should be conducted...
  24. ncbi Functional characteristics of N8, a new recombinant FVIII
    M L S Christiansen
    Biopharmaceutical Research Unit, Novo Nordisk A S, Måløv, Denmark
    Haemophilia 16:878-87. 2010
    ..The study demonstrated that N8 is fully functional in a variety of assays measuring FVIII activity. No functional differences were found between N8 and comparator compounds...
  25. pmc Recombinant canine B-domain-deleted FVIII exhibits high specific activity and is safe in the canine hemophilia A model
    Denise E Sabatino
    Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Blood 114:4562-5. 2009
    ..Infusion of cFVIII-BDD in hemophilia A dogs resulted in correction of the disease phenotype with a pharmacokinetic profile similar to clinical ..
  26. ncbi Prophylactic versus on-demand treatment strategies for severe haemophilia: a comparison of costs and long-term outcome
    K Fischer
    Department of Paediatrics, University Medical Center Utrecht, The Netherlands
    Haemophilia 8:745-52. 2002
    ..These findings suggest that, compared with a primarily on-demand treatment strategy, a primarily prophylactic treatment strategy leads to better outcome at equal treatment costs in young adults with severe haemophilia...
  27. ncbi Venous access in haemophilic children: choice and management
    E Santagostino
    Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation and University of Milan, Milan, Italy
    Haemophilia 16:20-4. 2010
    ..More recently, arteriovenous fistula was shown to be a suitable alternative to CVADs because it is easy to use and is associated with a lower rate of complication...
  28. ncbi Inhibitors against factor VIII in patients with cancer. Analysis of 41 patients
    S Sallah
    Department of Medicine, Division of Hematology Oncology, University of Tennessee, Memphis, Tennessee 38103, USA
    Cancer 91:1067-74. 2001
    ..However, to the authors' knowledge there is lack of information in the literature with respect to the clinical course of these patients and the nature of the association between malignant tumors and acquired hemophilia...
  29. ncbi Catalytic activity of antibodies against factor VIII in patients with hemophilia A
    S Lacroix-Desmazes
    INSERM U430 and Universite Pierre et Marie Curie, Hopital Broussais, 75014 Paris, France
    Nat Med 5:1044-7. 1999
    b>Hemophilia A is an X chromosome-linked recessive disorder resulting in defective or deficient factor VIII (FVIII) molecules, which, in its severe form, is a life-threatening and crippling hemorrhagic disease...
  30. pmc AAV-based neonatal gene therapy for hemophilia A: long-term correction and avoidance of immune responses in mice
    C Hu
    Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Gene Ther 19:1166-76. 2012
    b>Hemophilia A gene therapy has been hampered by immune responses to vector-associated antigens and by neutralizing antibodies or inhibitors against the factor VIII (FVIII) protein; these 'inhibitors' more commonly affect hemophilia A ..
  31. ncbi Barriers to compliance with prophylaxis therapy in haemophilia
    M R Hacker
    Mountain States Regional Hemophilia and Thrombosis Center, University of Colorado Health Sciences Center, Aurora, CO 80045 0507, USA
    Haemophilia 7:392-6. 2001
    ..In addition, this study underscores the importance of providing continuing support and education for patients and families who are implementing prophylaxis...
  32. ncbi Guidelines for the management of hemophilia
    A Srivastava
    Department of Hematology, Christian Medical College, Vellore, India
    Haemophilia 19:e1-47. 2013
    ....
  33. ncbi Haemophilias A and B
    Paula H B Bolton-Maggs
    Department of Haematology, Royal Liverpool Children s Hospital, Liverpool, UK
    Lancet 361:1801-9. 2003
    ..The future holds the realistic possibility of gene therapy. However, we must not forget that haemophilia is a worldwide disorder that requires significant economic resources not available for the majority...
  34. ncbi Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs
    Haiyan Jiang
    Avigen, Almeda, CA, USA
    Blood 108:107-15. 2006
    b>Hemophilia A, a deficiency of functional coagulation factor VIII (FVIII), is treated via protein replacement therapy...
  35. ncbi Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV
    Sarah C Darby
    Clinical Trial Service Unit, University of Oxford, Oxford, UK
    Blood 110:815-25. 2007
    ..This study presents mortality in 6018 people with hemophilia A or B in the United Kingdom during 1977 to 1998 who were not infected with HIV, with follow-up until January 1, ..
  36. ncbi Practice patterns in haemophilia A therapy -- global progress towards optimal care
    S Geraghty
    Mountain States Regional Haemophilia and Thrombosis Center, University of Colorado Health Sciences Center, Aurora, CO, USA
    Haemophilia 12:75-81. 2006
    ..Results from this current survey suggest that worldwide research should be continued so as to improve outcomes through the identification of optimal treatment protocols for the management of haemophilia A...
  37. ncbi Bioengineering of coagulation factor VIII for improved secretion
    Hongzhi Z Miao
    Department of Pediatrics, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    Blood 103:3412-9. 2004
    ..Quantitative or qualitative deficiencies of FVIII result in the inherited bleeding disorder hemophilia A. Expression of FVIII (domain structure A1-A2-B-A3-C1-C2) in heterologous mammalian systems is 2 to 3 orders of ..
  38. ncbi Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study
    Samantha C Gouw
    Van Creveldlkiniek, University Medical Center Utrrecht, Utrecht, The Netherlands
    Blood 109:4693-7. 2007
    ..This multicenter retrospective cohort study included 316 patients with severe hemophilia A born between 1990 and 2000...
  39. ncbi Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation
    Peter W Collins
    University Hospital of Wales and School of Medicine, Cardiff University, United Kingdom
    Blood 109:1870-7. 2007
    Acquired hemophilia A is a severe bleeding disorder caused by an autoantibody to factor VIII. Previous reports have focused on referral center patients and it is unclear whether these findings are generally applicable...
  40. pmc Inhibitors of factor VIII in black patients with hemophilia
    Kevin R Viel
    Southwest Foundation for Biomedical Research, San Antonio, TX, USA
    N Engl J Med 360:1618-27. 2009
    Black patients with hemophilia A (factor VIII deficiency) are twice as likely as white patients to produce inhibitors against factor VIII proteins given as replacement therapy...
  41. ncbi Sustained FVIII expression and phenotypic correction of hemophilia A in neonatal mice using an endothelial-targeted sleeping beauty transposon
    Li Liu
    Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USA
    Mol Ther 13:1006-15. 2006
    b>Hemophilia A, deficiency of coagulation factor VIII (FVIII), is an attractive candidate for gene therapy as expression of modest amounts of FVIII can provide therapeutic benefit...
  42. ncbi Recent progress in gene therapy for hemophilia
    Marinee K Chuah
    Department of Gene Therapy and Regenerative Medicine, Free University of Brussels, B 1090 Brussels, Belgium
    Hum Gene Ther 23:557-65. 2012
    b>Hemophilia A and B are X-linked monogenic disorders caused by deficiencies in coagulation factor VIII (FVIII) and factor IX (FIX), respectively...
  43. ncbi Compliance with treatment and understanding of own disease in patients with severe and moderate haemophilia
    K Lindvall
    Department of Coagulation Disorders, Malmo University Hospital, Malmo, Sweden
    Haemophilia 12:47-51. 2006
    ....
  44. ncbi Costs of on-demand and prophylactic treatment for severe haemophilia in Norway and Sweden
    K Steen Carlsson
    Department of Community Medicine, Malmö University Hospital and Lund University Centre for Health Economics, Lund University, Lund, Sweden
    Haemophilia 10:515-26. 2004
    ..For on-demand, the annual costs would increase by approximately the same proportion as an increase in the prescribed dose kg(-1)...
  45. ncbi Codon optimization of human factor VIII cDNAs leads to high-level expression
    Natalie J Ward
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Blood 117:798-807. 2011
    Gene therapy for hemophilia A would be facilitated by development of smaller expression cassettes encoding factor VIII (FVIII), which demonstrate improved biosynthesis and/or enhanced biologic properties...
  46. ncbi Inhibitor economics
    Jerome Teitel
    University of Toronto, Toronto, Ontario, Canada
    Semin Hematol 43:S14-7. 2006
    ..These outliers magnify overall treatment costs, making cost assessments for hemostatic therapy less predictable in patients with inhibitors than in those without inhibitors...
  47. ncbi Early long-term FEIBA prophylaxis in haemophilia A patients with inhibitor after failing immune tolerance induction: A prospective clinical case series
    C Escuriola Ettingshausen
    Centre for Paediatrics, Clinic III, Comprehensive Care Center for Thrombosis and Hemostasis, Johann Wolfgang Goethe University Hospital, Theodor Stern Kai 7, Frankfurt am Main, Germany
    Haemophilia 16:90-100. 2010
    ..The only adverse event involved venous access. Therefore early long-term FEIBA prophylaxis is valuable in controlling bleeding and preserving joint integrity in young patients failing ITI...
  48. ncbi Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors
    Cindy Leissinger
    Louisiana Center for Bleeding and Clotting Disorders, Tulane University, New Orleans, LA, USA
    N Engl J Med 365:1684-92. 2011
    Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease...
  49. ncbi New early prophylaxis regimen that avoids immunological danger signals can reduce FVIII inhibitor development
    K Kurnik
    Klinikum der Universitat Munchen, Dr von Haunersches Childrens Hospital, Munich, Germany
    Haemophilia 16:256-62. 2010
    ..048, 95% CI: 0.001-0.372). Our results indicate that minimizing danger signals during the first 20 EDs with FVIII may reduce the risk of inhibitor formation. These results should be confirmed in a larger prospective clinical study...
  50. ncbi Therapeutic factor VIII levels and negligible toxicity in mouse and dog models of hemophilia A following gene therapy with high-capacity adenoviral vectors
    Marinee K L Chuah
    Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Belgium
    Blood 101:1734-43. 2003
    ..human or canine factor VIII from different liver-specific promoters were evaluated for gene therapy of hemophilia A. Intravenous administration of these vectors into hemophilic FVIII-deficient immunodeficient SCID mice (FVIIIKO-..
  51. pmc High-dose factor VIII inhibits factor VIII-specific memory B cells in hemophilia A with factor VIII inhibitors
    Christina Hausl
    Biomolecular Therapeutics GmbH BMT Research, Vienna, Austria
    Blood 106:3415-22. 2005
    b>Hemophilia A in its severe form is a life-threatening hemorrhagic disease that is caused by mutations in the factor VIII (FVIII) gene (symbol F8)...
  52. ncbi Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimens
    P W Collins
    University Hospital of Wales, Arthur Bloom Hemophilia centre, Cardiff, Wales, UK
    J Thromb Haemost 8:269-75. 2010
    Prophylactic factor (F)VIII has been shown to reduce bleeds and arthropathy in patients with severe hemophilia A.
  53. ncbi Some factor VIII (FVIII) inhibitors recognise a FVIII epitope(s) that is present only on FVIII-vWF complexes
    J G Gilles
    Center for Molecular and Vascular Biology, University of Leuven, Belgium
    Thromb Haemost 82:40-5. 1999
    ..Patients carrying such an Arg2150His mutation and receiving infusion of wild-type FVIII may therefore be at risk of developing inhibitors to allogeneic FVIII only...
  54. ncbi Assessing health-related quality-of-life in individuals with haemophilia
    A H Miners
    Department of Primary Care and Population Sciences, Royal Free Hospital and University College Medical School, London, UK
    Haemophilia 5:378-85. 1999
    ..The results also suggest that the scope for primary prophylaxis to increase HR-QoL in individuals with severe haemophilia is significant...
  55. pmc Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation
    David W Scott
    Uniformed Services University for the Health Sciences, Bethesda, MD 20814, USA
    Br J Haematol 156:295-302. 2012
    ..In this review, we will describe the laboratory and clinical progress, and the challenges met thus far, in achieving the goal of gene therapy efficacy, with a focus on the goal of tolerance induction...
  56. pmc CD4+ T-cell epitopes associated with antibody responses after intravenously and subcutaneously applied human FVIII in humanized hemophilic E17 HLA-DRB1*1501 mice
    Katharina N Steinitz
    Baxter BioScience, Industriestrasse 72, Vienna, Austria
    Blood 119:4073-82. 2012
    ..Interestingly, most of the 8 peptide regions contained promiscuous epitopes that bound to several different HLA-DR proteins in in vitro binding assays...
  57. ncbi Validity of assessing inhibitor development in haemophilia PUPs using registry data: the EUHASS project
    K Fischer
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
    Haemophilia 18:e241-6. 2012
    ..After introduction of a new concentrate, the inhibitor incidence on this concentrate can only be reliably determined after an observation period of several years...
  58. ncbi Incidence of factor VIII inhibitors throughout life in severe hemophilia A in the United Kingdom
    Charles R M Hay
    Manchester University Department of Haematology, Manchester Royal Infirmary, Manchester, UK
    Blood 117:6367-70. 2011
    The age-adjusted incidence of new factor VIII inhibitors was analyzed in all United Kingdom patients with severe hemophilia A between 1990 and 2009...
  59. pmc Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A
    Johnny Mahlangu
    Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, University of the Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa
    Blood 123:317-25. 2014
    ..bleeding, and perioperative hemostatic control in 165 previously treated males aged ≥12 years with severe hemophilia A. The study had 3 treatment arms: arm 1, individualized prophylaxis (25-65 IU/kg every 3-5 days, n = 118); arm 2,..
  60. pmc Genetic induction of immune tolerance to human clotting factor VIII in a mouse model for hemophilia A
    G L Evans
    Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, MSC 1851, Building 10, Room 10C103, Bethesda, MD 20892 1851, USA
    Proc Natl Acad Sci U S A 95:5734-9. 1998
    ..Here, we report that in a factor VIII (FVIII)-deficient mouse model for severe hemophilia A, genetic modification of donor bone marrow cells with a retroviral vector encoding hFVIII, and transplant to ..
  61. pmc Past, present and future of hemophilia: a narrative review
    Massimo Franchini
    Immunohematology and Transfusion Center, Department of Pathology and Laboratory Medicine, University Hospital of Parma, Milan, Italy
    Orphanet J Rare Dis 7:24. 2012
    ..Finally, intensive research is devoted to gene transfer therapy, the only way to ultimately obtain cure in hemophilia...
  62. ncbi Heritable skewed X-chromosome inactivation leads to haemophilia A expression in heterozygous females
    Nisa K Renault
    Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
    Eur J Hum Genet 15:628-37. 2007
    ..Further, the findings suggest that these XCI ratios are genetically influenced, consistent with a novel heritable human X controlling element (XCE) functioning similarly to the mouse Xce...
  63. ncbi CD4+ T-cell clones specific for wild-type factor VIII: a molecular mechanism responsible for a higher incidence of inhibitor formation in mild/moderate hemophilia A
    Marc Jacquemin
    Center for Molecular and Vascular Biology, University of Leuven, Belgium
    Blood 101:1351-8. 2003
    Mild/moderate hemophilia A patients carrying certain mutations in the C1 domain of factor VIII (FVIII) have a higher risk of inhibitor occurrence...
  64. pmc Models for prediction of factor VIII half-life in severe haemophiliacs: distinct approaches for blood group O and non-O patients
    Kathelijn Fischer
    Van Creveldkliniek, Department of Haematology, University Medical Center Utrecht, Utrecht, The Netherlands
    PLoS ONE 4:e6745. 2009
    ..Von Willebrand factor (VWF) is critical for the in vivo survival of factor VIII (FVIII). Since FVIII half-life correlates with VWF-antigen pre-infusion levels, we hypothesized that VWF levels are useful to predict FVIII half-life...
  65. ncbi Acquired hemophilia A associated with therapeutic cupping
    Yi Ming Weng
    Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou, Kuei Shan Hsiang, Taoyuan Hsien, Taiwan
    Am J Emerg Med 26:970.e1-2. 2008
    Acquired hemophilia A is defined as the development of factor VIII inhibitors in a nonhemophilic patient...
  66. ncbi Assessing the costs for clinical care of patients with high-responding factor VIII and IX inhibitors
    M Ullman
    The University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, USA
    Haemophilia 12:74-9; discussion 79-80. 2006
    ....
  67. ncbi Factor VIIa analog has marked effects on platelet function and clot kinetics in blood from patients with hemophilia A
    Donald F Brophy
    School of Pharmacy, Coagulation Advancement Laboratory, Virginia Commonwealth University, Richmond, VA, USA
    Blood Coagul Fibrinolysis 21:539-46. 2010
    ..HAS and TEG assays provided similar estimates of FOT and R, however CEM appeared to be more sensitive than MA to changes in clot firmness...
  68. ncbi Hemophilia. Treatment of patients with inhibitors: cost issues
    J Goudemand
    Haematology Department, Centre Hospitalier r egional et Universitaire, Lille, France
    Haemophilia 5:397-401. 1999
    ..So there is no doubt that rFVIIa offers new perspectives in the therapeutic management of HR patients, but creates a new economic situation which needs further evaluation...
  69. ncbi Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A
    Richard D Bagnall
    Division of Medical and Molecular Genetics, Guy s, King s, and St Thomas School of Medicine, London, United Kingdom
    Blood 99:168-74. 2002
    The messenger RNA (mRNA) from 5 of 69 patients with severe hemophilia A did not support amplification of complementary DNA containing the first few exons of the factor VIII (F8) gene but supported amplification of mRNA containing exon 1 ..
  70. ncbi The therapeutic effect of bone marrow-derived liver cells in the phenotypic correction of murine hemophilia A
    Neelam Yadav
    Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India
    Blood 114:4552-61. 2009
    ..VIII (FVIII) synthesis, we hypothesized that the partial replacement of mutated liver cells by healthy cells in hemophilia A mice could manage the severity of the bleeding disorder...
  71. ncbi Reduction of the inhibitory antibody response to human factor VIII in hemophilia A mice by mutagenesis of the A2 domain B-cell epitope
    Ernest T Parker
    Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
    Blood 104:704-10. 2004
    Approximately 25% of patients with hemophilia A develop inhibitory antibodies after treatment with factor VIII. Most of the inhibitory activity is directed against epitopes in the A2 and C2 domains...
  72. ncbi Clinical issues in inhibitors
    J Astermark
    Centre for Thrombosis and Haemostasis, Skane University Hospital, Malmo, Sweden
    Haemophilia 16:54-60. 2010
    ..Each of these strategies is discussed in the context of their relative benefits and risks...
  73. pmc PEGylation of a factor VIII-phosphatidylinositol complex: pharmacokinetics and immunogenicity in hemophilia A mice
    Aaron Peng
    Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, 14260, USA
    AAPS J 14:35-42. 2012
    b>Hemophilia A is an X-linked bleeding disorder caused by the deficiency of factor VIII (FVIII). Exogenous FVIII is administered therapeutically, and due to a short half-life, frequent infusions are often required...
  74. ncbi Recombinant vs. plasma-derived products, especially those with intact VWF, regarding inhibitor development
    C Escuriola Ettingshausen
    Centre of Paediatrics III, Department of Haematology, Oncology and Haemostaseology, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany
    Haemophilia 12:102-6. 2006
    ..However, in order to provide more evidence a well-designed randomized study is needed...
  75. pmc Antihuman factor VIII C2 domain antibodies in hemophilia A mice recognize a functionally complex continuous spectrum of epitopes dominated by inhibitors of factor VIII activation
    Shannon L Meeks
    Aflac Cancer Center and Blood Disorders Service, Children s Healthcare of Atlanta, Department of Pediatrics, Emory University, Atlanta, GA, USA
    Blood 110:4234-42. 2007
    ..These results reveal the structural and functional complexity of the anti-C2 domain antibody response and indicate that interference with fVIII activation is a major attribute of the inhibitor landscape...
  76. ncbi Thrombin generation in severe haemophilia A and B: the endogenous thrombin potential in platelet-rich plasma
    Thomas Siegemund
    Clinical Haemostaseology, Medical Clinic I, University of Leipzig, Leipzig, Germany
    Thromb Haemost 90:781-6. 2003
    ..In conclusion, there is a difference in thrombin generation between haemophilia A and B, and this may be attributed to the role of platelets in the assembly of the tenase complex on their surface...
  77. ncbi Simultaneous detection and epitope mapping of anti-factor VIII antibodies
    Géraldine Lavigne-Lissalde
    CNRS FRE 3009, Cap Delta Parc Euromédecine, Montpellier, France
    Thromb Haemost 99:1090-6. 2008
    ..This technology appears attractive as it is fast and requires only 100 microl of patient's plasma. Furthermore, not only are anti-FVIII Abs detected, but information on their epitopic specificity is also obtained...
  78. ncbi Recombinant factor VIII concentrates
    Massimo Franchini
    Servizio di Immunoematologia e Medicina Trasfusionale, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero Universitaria di Parma, Parma, Italy
    Semin Thromb Hemost 36:493-7. 2010
    ..factor VIII (rFVIII) concentrates nearly 20 years ago represented a major advance in the treatment of hemophilia A patients. Currently, first-, second- and third-generation rFVIII products are commercially available...
  79. ncbi Acquired hemophilia a: diagnosis, aetiology, clinical spectrum and treatment options
    Shrimati Shetty
    National Institute of Immunohematology ICMR, 13th Floor, KEM Hospital, Parel, Mumbai 400 012, India
    Autoimmun Rev 10:311-6. 2011
    Acquired hemophilia A (AHA) is a rare disorder with an incidence of approximately 1 per million/year with a high mortality rate of more than 20%...
  80. ncbi Longer-acting factor VIII to overcome limitations in haemophilia management: the PEGylated liposomes formulation issue
    G Di Minno
    Department of Medicine, Federico II University, Reference Centre for Hemophilia and Thrombosis, Naples, Italy
    Haemophilia 16:2-6. 2010
    ..Data emerging from this phase II study will help collect relevant data to overcome current limitations in haemophilia management by employing treatment with longer-acting rFVIII...
  81. ncbi Total knee replacement in haemophilia
    N J Goddard
    Department of Orthopaedics, Royal Free Hospital School of Medicine, London, UK
    Haemophilia 8:382-6. 2002
    ..The latest techniques have gone a long way to reducing the complication rate and to achieving results that match those of a similar non-haemophiliac population...
  82. ncbi Analysis of 18 novel mutations in the factor VIII gene
    Maria P Bicocchi
    Haemostasis and Haemophilia Laboratory, IV Paediatric Department, G Gaslini Institute, Genova, Italy
    Br J Haematol 122:810-7. 2003
    ..These research tools have provided evidence that the mutations we describe involve residues that were conserved, at least in FVIII proteins, in all the species we compared...
  83. ncbi Factor VIII inhibitors: risk factors and methods for prevention and immune modulation
    Ai Hong Zhang
    Department of Surgery, and Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, 800 West Baltimore Street, Room 319, Baltimore, MD 21201, USA
    Clin Rev Allergy Immunol 37:114-24. 2009
    Patients with hemophilia A are deficient in coagulation Factor VIII...
  84. ncbi Precise carrier diagnosis in families with haemophilia A: use of conformation sensitive gel electrophoresis for mutation screening and polymorphism analysis
    I J Williams
    Division of Molecular and Genetic Medicine, Royal Hallamshire Hospital, Sheffield, UK
    Thromb Haemost 79:723-6. 1998
    ..Conformation sensitive gel electrophoresis was found to be technically simple and efficient at locating previously unknown FVIII gene mutations...
  85. ncbi Assessing risk factors: prevention of inhibitors in haemophilia
    H Chambost
    Service d Hématologie Pédiatrique, Hôpital d Enfants La Timone, Universite de la Mediterranee, Marseille, France
    Haemophilia 16:10-5. 2010
    ..Through a more complete picture of a patient's overall risk profile, individually tailored treatment schedules might be developed that could minimize the incidence of inhibitor formation and thus maximize therapeutic benefit...
  86. ncbi The identification and classification of 41 novel mutations in the factor VIII gene (F8C)
    J A Cutler
    The Haemophilia Reference Centre, Centre for Thrombosis and Haemostasis, St Thomas Hospital, Lambeth Palace Road, London, UK
    Hum Mutat 19:274-8. 2002
    b>Hemophilia A is a bleeding disorder caused by a quantitative or qualitative deficiency in the coagulation factor VIII. Causative mutations are heterogeneous in nature and are distributed throughout the FVIII gene...
  87. ncbi Total knee replacement in haemophilic arthropathy
    E C Rodriguez-Merchan
    Department of Orthopaedics and Haemophilia Unit, La Paz University Hospital, Paseo de la Castellana 261, 28046 Madrid, Spain
    J Bone Joint Surg Br 89:186-8. 2007
    ..Our rate of infection was lower than previously reported. This could be due to better control of the HIV status with highly active anti-retroviral therapy and the use of antibiotic-loaded cement...
  88. ncbi Safety profile of recombinant factor VIIa
    Harold R Roberts
    Division of Hematology, Center for Thrombosis and Hemostasis, University of North Carolina at Chapel Hill, USA
    Semin Hematol 41:101-8. 2004
    ..Finally, those situations in which rFVIIa therapy may not be safe, such as disseminated intravascular coagulation (DIC) and sepsis, will also be discussed...
  89. ncbi Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment
    Baisong Mei
    Global Biological Development, Bayer HealthCare LLC, Berkeley, CA, USA
    Blood 116:270-9. 2010
    A long-acting factor VIII (FVIII) as a replacement therapy for hemophilia A would significantly improve treatment options for patients with hemophilia A...
  90. pmc Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1 or MCFD2
    Bin Zhang
    Life Sciences Institute, Department of Internal Medicine, 210 Washtenaw Ave, Ann Arbor, MI 48109 0650, USA
    Blood 107:1903-7. 2006
    ....
  91. ncbi Uncertain times for research on hemophilia and allied disorders
    P M Mannucci
    J Thromb Haemost 3:423. 2005
  92. ncbi Long-term efficacy of adeno-associated virus serotypes 8 and 9 in hemophilia a dogs and mice
    Rita Sarkar
    Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104 6145, USA
    Hum Gene Ther 17:427-39. 2006
    ..FVIII) activity, using adeno-associated virus serotype 8 (AAV8) vectors for liver-specific gene transfer in hemophilia A mice...
  93. ncbi Neutralization of antifactor VIII inhibitors by recombinant porcine factor VIII
    R T Barrow
    Aflac Cancer Center and Blood Disorders Service, Children s Healthcare of Atlanta, Atlanta, GA 30322, USA
    J Thromb Haemost 4:2223-9. 2006
    ..antibodies to factor (F) VIII (FVIII inhibitors) present a major clinical challenge as a complication of hemophilia A and as acquired autoantibodies in non-hemophiliacs...
  94. doi Factor VIII products and inhibitor development: the SIPPET study (survey of inhibitors in plasma-product exposed toddlers)
    P M Mannucci
    A Bianchi Bonomi Hemophilia and Thrombosis Centre, Department of Medicine and Medical Specialties, University of Milan, Italy
    Haemophilia 13:65-8. 2007
  95. pmc Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy
    Jonathan D Finn
    Department of Hematology, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 116:5842-8. 2010
    Inhibitory antibodies to factor VIII (FVIII) are a major complication in the treatment of hemophilia A, affecting approximately 20% to 30% of patients...
  96. ncbi Mortality and causes of death in Italian persons with haemophilia, 1990-2007
    A Tagliaferri
    Regional Reference Centre for Inherited Bleeding Disorders, University Hospital, Parma, Italy
    Haemophilia 16:437-46. 2010
    ..The results of this retrospective study show that in Italian PWH improvements in the quality of treatment and global medical care provided by specialized haemophilia centres resulted in a significantly increased life expectancy...
  97. ncbi Total knee arthroplasty in hemophilic arthropathy
    John M Norian
    University of California, San Francisco, San Francisco, CA 94143, USA
    J Bone Joint Surg Am 84:1138-41. 2002
    ..The purpose of this study was to evaluate prosthetic survival following total knee arthroplasty and identify factors associated with failures of the arthroplasties in hemophilic patients...
  98. ncbi Orthopaedic issues in sports for persons with haemophilia
    Axel Seuser
    Kaiser Karl Klinik, Department of Orthopaedics, Bonn, Germany
    Haemophilia 13:47-52. 2007
    ..With proper physical evaluation and preparation, patients with haemophilia can realize the physical and emotional benefits of participation in sports...
  99. ncbi Engineered factor IX variants bypass FVIII and correct hemophilia A phenotype in mice
    Peter Milanov
    Institute for Transfusion Medicine and Immune Hematology, German Red Cross Blood Donor Service Baden Wuerttemberg Hessen, Clinics of the Johann Wolfgang Goethe University, Germany
    Blood 119:602-11. 2012
    ..Whereas substitution of FVIII is the mainstay of hemophilia A therapy, treatment of patients with inhibitory Abs remains challenging...
  100. ncbi Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: a systematic review
    A Iorio
    Internal and Vascular Medicine and Hemophilia Centre, University of Perugia, Perugia, Italy
    J Thromb Haemost 8:1256-65. 2010
    ..Different rates of inhibitor development after either plasma-derived (pdFVIII) or recombinant (rFVIII) FVIII have been suggested. However, conflicting results are reported in the literature...
  101. ncbi Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA
    M Higuchi
    Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
    Genomics 6:65-71. 1990
    In order to search for mutations resulting in hemophilia A that are not detectable by restriction analysis, three regions of the factor VIII gene were chosen for direct sequence analysis...

Research Grants68

  1. Regulation of factor VIII Levels and Activity by Members of LDL Receptor Family
    Dudley K Strickland; Fiscal Year: 2013
    ..VIII (fVIII) and factor IX (fIX) are two key plasma proteins that are deficient in the bleeding disorders Hemophilia A and Hemophilia B, respectively...
  2. Platelet-Derived FVIII Gene Therapy of Hemophilia A
    Qizhen Shi; Fiscal Year: 2013
    ..The development of inhibitory antibodies to exogenous FVIII is an important complication of FVIII infusion in hemophilia A patients. Generation of such inhibitors might have the potential to preclude gene therapy for hemophilia A...
  3. Mechanisms of Race-Based Differences in Factor VIII Immunogenicity in Hemophilia
    KATHLEEN PALMER PRATT; Fiscal Year: 2010
    ..will elucidate mechanisms of immune responses to the infused factor VIII (FVIII) used to arrest bleeding in hemophilia A (HA) patients, in which ~25% of patients develop "inhibitors" (neutralizing antibodies) that can greatly ..
  4. Phase 2a Study of Ataluren in Hemophilia A and B (IND 104,321)
    JAY A BARTH; Fiscal Year: 2010
    ..activity, safety, and pharmacokinetic study of ataluren in patients with nonsense-mutation-mediated hemophilia A and B (HA/HB), rare and life-threatening genetic disorders...
  5. Hematopoietic gene therapy for hemophilia A
    H Trent Spencer; Fiscal Year: 2013
    b>Hemophilia A is a congenital bleeding disorder caused by genetic mutations affecting a plasma protein, termed factor VIII (fVIII), whose function is to facilitate blood clotting...
  6. Oral Therapy for Hemophilia A
    Kam W Leong; Fiscal Year: 2013
    ..Upon treatment, 20-30% of patients with hemophilia A (factor VIII deficiency) and 1...
  7. Therapeutic-Expression of a Platelet-Specific Integrin
    DAVID ALLEN WILCOX; Fiscal Year: 2010
    ..In Specific Aim 3, an allb-driven lentivirus will be used to explore strategies to correct canine Hemophilia A via targeted synthesis and storage of coagulation factor VIII to platelet a-granules...
  8. Prevention of the Complications of Hemophilia Thru Hemophilila Treatment Centers
    MD WALSH; Fiscal Year: 2010
    ..HTC's are designed to treat patients with hemophilia A and B, von Willebrand Disease and rare factor deficiencies...
  9. In vivo lentiviral transduction of bone marrow cells for hemophilia gene therapy
    Carol H Miao; Fiscal Year: 2013
    PROJECT SUMMARY The goal of this proposal is to develop an effective gene therapy strategy to treat hemophilia A (HemA) by directly transferring lentiviral vectors encoding factor VIII (FVIII) gene into bone marrow cells...
  10. RAMP Mediated Gene Delivery
    Kevin G Rice; Fiscal Year: 2012
    ....
  11. Induction of Tolerance to Factor VIII in Hemophilia
    DAVID WILLIAM SCOTT; Fiscal Year: 2012
    b>Hemophilia A is an X-linked disorder in which clotting factor VIII (fVIII) mutations lead to a loss of fVIII expression and serious bleeding...
  12. Bioengineered factor VIII gene therapy for hemophilia A
    H Trent Spencer; Fiscal Year: 2012
    ..studies to support a pilot clinical trial of hematopoietic stem cell transplantaton gene therapy for hemophilia A. In a series of recent studies, we have shown that the transplantation of genetically-engineered hematopoietic ..
  13. Structure and Stability Studies of Factor VIII to Overcome the Immune Response
    PAUL CLINTON SPIEGEL; Fiscal Year: 2010
    ..Genetic deficiencies in factor VIII cause hemophilia A, which affects 1 in 5,000 males worldwide...
  14. Blocking the immune response to Helper-dependent adenovirus vector for Hemophilia
    Masataka Suzuki; Fiscal Year: 2011
    ..Blocking the immune response to Helper-dependent adenovirus vector for improved Hemophilia A gene therapy. Project Abstract...
  15. The Activation of Prothrombin
    Kenneth G Mann; Fiscal Year: 2011
    ..Hemorrhagic diseases, especially hemophilia A and B are thankfully less frequent, but still major health issues for those affected...
  16. STRUCTURE AND REGULATION OF HUMAN FACTOR VIII
    Philip J Fay; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Hemophilia A, the most common of the severe, inherited bleeding disorders, results from a deficiency or defect in factor VIII...
  17. Blocking the immune response to HDAd for Hemophilia A gene therapy
    Masataka Suzuki; Fiscal Year: 2013
    Project Title. Blocking the immune response to Helper-dependent adenovirus vector for improved Hemophilia A gene therapy. Project Abstract. Hemophilia A (HA) is a common disorder of coagulation caused by deficiency of factor VIII (FVIII)...
  18. Transplantation of Endothelial Cells
    Sanjeev Gupta; Fiscal Year: 2013
    ..ability of transplanted LSEC to synthesize and release FVIII permitted us to achieve permanent correction of hemophilia A in a mouse model...
  19. Hemophilia Adult Prophylaxis Study
    MARGARET VICTORIA RAGNI; Fiscal Year: 2012
    ..FVIII) prophylaxis in adults with severe hemophilia A. This will be accomplished by 1) conducting a pilot clinical trial at six core hemophilia treatment centers (..
  20. Mechanisms of Immunogenicity of Factor VIII
    Shannon L Meeks; Fiscal Year: 2013
    ..applicant): Inhibitory antibodies to factor VIII (fVIII) develop in approximately 30% of patients with severe hemophilia A in response to infusions of fVIII...
  21. Regulation of Targeted Gene Correction
    Eric B Kmiec; Fiscal Year: 2012
    ..Crigler-Naiiar. OTC. MPSVII. Hemophilia A and B and many lysosomal storage disorders among others...
  22. In vivo function and tolerance to Factor VIII variants
    BRENDAN HL LEE; Fiscal Year: 2011
    b>Hemophilia A (HA) is a common disorder of coagulation caused by deficiency of factor VIII (FVIII). The mainstay of therapy has been replacement therapy with recombinant human FVIII...
  23. Biological Variation in Hemophilia
    JOHN S LOLLAR; Fiscal Year: 2013
    FVIII (fVIII) replacement therapy is the mainstay of the management of congenital hemophilia A in developed countries...
  24. Feasibility of the Hemophilia INHIBIT Trial
    MARGARET VICTORIA RAGNI; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Hemophilia A is an X-linked bleeding disorder resulting from deficiency of factor VIII, and characterized by bleeding into joints, muscles, and body cavities...
  25. FIV Vectors for the Treatment of Hemophilia A
    William C Raschke; Fiscal Year: 2012
    ..by applicant): Although several labs including ours have demonstrated the feasibility of gene therapy for hemophilia A in animal models, long-term expression of the transgene at therapeutic levels was not observed in the clinic...
  26. Retrotransposition in Health and Disease
    Haig H Kazazian; Fiscal Year: 2013
    ..Since we found the first disease-causing insertions of an L1 in two patients with hemophilia A some 23 years ago, much has been learned about L1 and other human retrotransposons through cell culture assays, ..
  27. Combined Factor VIII Replacement and Tolerance Therapy for Hemophilia A
    ANNE SEARLS DEGROOT; Fiscal Year: 2013
    ..and immunomodulatory therapy that will provide FVIII-specific tolerance induction at therapeutic doses for Hemophilia A patients...
  28. Regulation of Factor FVIII Secretion
    Randal J Kaufman; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Factor VIII (FVIII) is the protein deficient or functionally defective in hemophilia A, an X chromosome-linked bleeding disorder affecting 1/5,000 males...
  29. Transfusion Medicine/Hemostasis Core Clinical Center
    Thomas L Ortel; Fiscal Year: 2012
    ..In contrast, many hemostatic disorders, such as thrombotic thrombocytopenic purpura (TTP) and hemophilia A patients with inhibitors, are relatively rare, making it difficult to answer important clinical questions due ..
  30. AAV-Mediated Gene Therapy for Hemophilia
    Andrew M Davidoff; Fiscal Year: 2013
    ..mediate long-term expression of therapeutic levels of coagulation factor VIII (FVIII) for the treatment of hemophilia A. We have already used this approach to safely generate stable, therapeutic levels of coagulation factor IX (FIX)..
  31. VWF Multimer Distribution a Phenotypic Modifier of Hemophilia A
    CHAR MARIE WITMER; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Abstract Hemophilia A is the most common severe congenital bleeding disorder and is the result of a deficiency of the clotting factor (F) VIII...
  32. Epitope-driven deimmunization of Factor VIII
    ANNE SEARLS DE GROOT; Fiscal Year: 2010
    b>Hemophilia A patients are prone to develop inhibitory immune responses to the very therapy they require: Factor VIII protein replacement...
  33. ER-to-Golgi transport of coagulation factors V and VIII
    Bin Zhang; Fiscal Year: 2013
    ..Genetic deficiency of FVIII results in hemophilia A, which affects ~1 in 5000 males...
  34. Development and Pharmacology of Novel Lipidic rAHF
    SATHY VENKAT BALU-IYER; Fiscal Year: 2013
    ..The deficiency and dysfunction of FVIII causes Hemophilia A, a bleeding disorder...
  35. MAINTENANCE OF ANIMAL MODELS OF HUMAN HEMOPHILIA AND VWD
    TIMOTHY CHARLES NICHOLS; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The purpose of this resource grant is to maintain and create dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and FVII deficiency for independent and collaborative research...
  36. Investigation of protein interactions in intrinsic blood coagulation pathway
    Divi Venkateswarlu; Fiscal Year: 2007
    ..in intrinsic pathway? And iv) Can we decipher the structure-function correlation between the vast amount of hemophilia A and B patient mutational database and the proposed structural models, and if yes, can one use the protein- ..
  37. Immunology of Factor IX Gene Transfer to Liver
    Roland W Herzog; Fiscal Year: 2013
    ..Finally, we will extent investigations on the immunology of hepatic AAV gene transfer to treatment of hemophilia A (factor VIII, F.VIII, deficiency), the more common form of hemophilia. F...
  38. Region V-East HTC Network for the Prevention of Bleeding Disorders Complications
    IVAN C HARNER; Fiscal Year: 2010
    ..of the cohort and the refinement of data collected to continue to characterize sub-populations, including hemophilia A and B, women with bleeding disorders, von Willebrand disease, and rare bleeding disorders...
  39. GENE THERAPY FOR HEMOPHILIA
    Katherine A High; Fiscal Year: 2013
    ..VIII activity in the presence of inhibitors in both hemophilia A mice and dogs...
  40. GENE THERAPY FOR HEMOPHILIA
    Mark Kay; Fiscal Year: 2005
    ..2) Dr. Haig Kazazian and colleagues will build on their success in treating hemophilia A mice using new AAV serotypes...
  41. Fine epitope mapping of B cell response in patients with hemophilia A: Pilot
    Shannon L Meeks; Fiscal Year: 2013
    ..This is the most significant complication in the management of patients with hemophilia A leading to increases in morbidity as well as cost of treatment...
  42. Preclinical gene correction of hemophilia A
    Haig H Kazazian; Fiscal Year: 2010
    This proposal sets the stage for clinical trials of gene therapy for hemophilia A. Here we concentrate on the use of adeno-associated viral (AAV) vectors with new capsid serotypes for liver directed gene therapy in a large animal model, ..
  43. Structural studies of blood coagulation proteins
    Barry Stoddard; Fiscal Year: 2006
    ..A wide variety of inheritable coagulation deficiencies are associated with mutations in factor VIII (hemophilia A), factor IX (hemophilia B) and von Willebrand Factor (von Willebrand Disease)...
  44. Prevention of the Complications of Bleeding Disorders
    DOREEN B BRETTLER; Fiscal Year: 2010
    ..the cohort through continued recruitment and observations of individuals with bleeding disorders including hemophilia A and Hemophilia B, von Willebrand disease, rare bleeding disorders, and women with bleeding disorders: (2) ..
  45. Evaluation of the Antigenicity of Black Restricted FVIII Haplotypes and Haplotype
    James W Lillard; Fiscal Year: 2013
    Evaluation of the Antigenicity of Black-Restricted Haplotypes of Factor VIII ABSTRACT About 30% of congenital Hemophilia A (HA) patients develop alloantibodies that neutralize the activity of replacement Factor (F) VIII proteins...
  46. Inhibitor development in patients with hemophilia A undergoing surgery
    CHRISTINE LUISE KEMPTON; Fiscal Year: 2013
    ..VIII (fVIII) antibodies, inhibitors, is the most significant complication affecting treated patients with hemophilia A (HA). Once an inhibitor develops, treatment is less effective and costly...
  47. BIOLOGIC AND IMMUNOLOGIC ASPECTS OF TRANSFUSION MEDICINE
    Sherrill Slichter; Fiscal Year: 2009
    ..related to the prevention or reversal of inhibitor antibody formation in patients with acquired or congenital hemophilia A. Modification of T-cell epitopes in FVIII may lead to non-immunogenic FVIII replacement therapy while new ..
  48. TMH Clinical Trials Network-Wisconsin Core Clinical Center
    JANICE G MC FARLAND; Fiscal Year: 2012
    ..of Hemostasis and Invasive Procedures" (SHIP), and "Rituximab for the treatment of Inhibitors in Congenital Hemophilia A" (RICH)) and to add to these, new trials as they are approved (e.g...
  49. Patient-Level Meta-analysis: Effect of age of initiation, intensity and duration
    Marilyn J Manco-Johnson; Fiscal Year: 2013
    ..Abstract: This proposal will address the development of structural and functional joint disease in severe hemophilia A along with the benefits of prophylaxis in preventing or ameliorating joint damage...
  50. Molecular engineering of factor VIII gene for rAAV delivery
    Weidong Xiao; Fiscal Year: 2012
    Approximately one in 5000 males in human population suffers from coagulation disorder, hemophilia A. This disease is primarily caused by deficiency in the factor VIII gene located in the X-chromosome and is difficult to treat by ..
  51. Novel Reagents to Bypass Limitations of Existing Coagulation Assays
    Stephen Burgess; Fiscal Year: 2009
    ..Blood coagulation assays are required to diagnose bleeding disorders such as hemophilia A and B and to provide physicians with information essential to surgery and to emergency medical situations...
  52. Hemophilia A: Intrathymic Delivery for Tolerance and Longterm Expression of FVIII
    William Raschke; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): The current standard of care for hemophilia A is treatment with intravenous human factor VIII (hFVIII) protein infusions, either prophylactically or during bleeding episodes...
  53. DDAVP IN CONGENITAL PLATELET FUNCTION DISORDERS
    A Rao; Fiscal Year: 1990
    ..FVIII:RAg and FVIII:RCo on intravenous administration in normal subjects and patients with milder vWD and hemophilia A and has been approved recently by FDA for treatment of such patients...
  54. In Utero Stem Cell Transplantation for Hemophilia A
    Graca Almeida Porada; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): Hemophilia A is an X-linked recessive bleeding disorder caused by the deficiency/abnormality of Factor VIII...
  55. Generation of interfering RNA molecules by trans-splicing
    COLETTE COTE; Fiscal Year: 2006
    ..PTMs and SMaRT have been used to correct genetic disorders in mice (e.g. hemophilia A), to image tumor cells in living animals, and to attempt suicide gene therapy of virally infected cells in ..
  56. Fluorogenic Assays for Factor Vlla and Tissue Factor
    RICHARD JENNY; Fiscal Year: 2006
    ..In addition, over the past decade recombinant factor VIla has become the drug of choice for treating hemophilia A and B patients who have developed inhibitors to factors VIII and IX respectively...
  57. ANALYSIS OF FACTOR VIII COAGULANT ANTIGEN
    Mark Weinstein; Fiscal Year: 1990
    ..vWF) structure and concentration occur not only in inherited coagulation disorders such as vWF disease and hemophilia A but in acquired disorders including renal dysfunction, disseminated intravascular coagulation, heart disease, ..
  58. EPITOPES OF ANTIFACTOR VIII ANTIBODIES IN HEMOPHILIACS
    Dorothea Scandella; Fiscal Year: 1999
    ..coagulation factor VIII (FVIII inhibitors) develop in up to 37% of repeatedly transfused patients with severe hemophilia A. Although the effects of inhibitors are variable, significant bleeding and disability are frequent, and they ..
  59. COMPARATIVE STUDY OF COAGULATION AND VASCULAR DISEASE
    WINIFRED DODDS; Fiscal Year: 1993
    ..These include dos with hemophilia A, hemophilia B, von Willebrand's disease (vWD), factor VII deficiency, thrombasthenia, and thrombopathia...
  60. Gene Therapy for Muscular Dystrophy
    Hengjun Chao; Fiscal Year: 2009
    ..We recently reported repair of the large size FVIII gene and the consequential hemophilia A phenotype correction by using a novel RNA repair strategy: splicesome- mediated RNA trans-splicing (SMaRT)...
  61. GENETICS OF INHIBITOR FORMATION IN HEMOPHILIA
    Joan Gill; Fiscal Year: 2001
    b>Hemophilia A is a severe hemorrhagic disorder due to deficiency of coagulation factor VIII. Approximately 15 to 20 percent of severely affected patients develop antibodies to factor VIII with replacement therapy...
  62. Repair of Factor VIII by targeted RNA trans splicing
    S Mansfield; Fiscal Year: 2003
    Successful gene therapy will revolutionize the treatment of the inherited bleeding disorders hemophilia A and B. Hemophilia A is caused by deficiency of coagulation factor VIII (FVIII) and is a prime disorder for genetic correction...
  63. TARGETED GENE THERAPY FOR HEMOPHILIA A
    Wadie Bahou; Fiscal Year: 2003
    b>Hemophilia A (congenital deficiency of coagulation factor VIII) is the most common (serious) congenital bleeding disorder worldwide...
  64. Repair of Factor VIII by targeted RNA trans-splicing
    S Mansfield; Fiscal Year: 2006
    ..by applicant): Successful gene therapy will revolutionize the treatment of the inherited bleeding disorders hemophilia A and B...
  65. Molecular Chimerism Therapy for Hemophilia A
    Robert Hawley; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Hemophilia A is an X-linked recessive genetic bleeding disorder caused by a deficiency or functional defect in coagulation factor VIII (FVIII)...
  66. CATABOLISM OF COAGULATION FACTOR VIII
    Evgueni Saenko; Fiscal Year: 2004
    ..for haemostasis, since genetic defects in this molecule cause a life-threatening coagulation disorder known as Hemophilia A. This genetic disease is treated by repeated infusions of expensive fVIII products...
  67. GENE THERAPY FOR BLOOD PROTEIN DEFICIENCIES
    KATHERINE PONDER; Fiscal Year: 2005
    ..of coagulation factors from the liver in rodents, and are currently being used in a clinical trial for Hemophilia A in humans...
  68. Translational Bypass in Patients with Hemophilia
    Steve Sommer; Fiscal Year: 2003
    ..Hemophilia is chosen as the model disease. Major effects of severe hemophilia A)B can be eliminated with only a slight increase in factor level...