factor viii

Summary

Summary: Blood-coagulation factor VIII. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin.

Top Publications

  1. 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
  2. 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
  3. ncbi Modern haemophilia care
    Erik Berntorp
    Lund University, Malmö Centre for Thrombosis and Haemostasis, Skane University Hospital, Malmo, Sweden
    Lancet 379:1447-56. 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. 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
  6. 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
  7. ncbi Purification and characterization of a new recombinant factor VIII (N8)
    L Thim
    Biopharmaceutical Research Unit, Novo Nordisk A S, Maaloev, Denmark
    Haemophilia 16:349-59. 2010
  8. ncbi Factor VIII and von Willebrand factor interaction: biological, clinical and therapeutic importance
    V Terraube
    Haemostasis Research Group, Institute of Molecular Medicine, Trinity College, Dublin, Ireland
    Haemophilia 16:3-13. 2010
  9. ncbi Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia
    John A Livesey
    Imperial College School of Medicine, Imperial College, London, UK
    Thorax 67:328-33. 2012
  10. 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

Detail Information

Publications332 found, 100 shown here

  1. 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
    ..6-1.5), and the risk in small deletions/insertions and missense mutations was lower (pooled OR = 0.5; 95% CI, 0.4-0.6 and OR = 0.3; 95% CI, 0.2-0.4, respectively). The relative risks for developing high titer inhibitors were similar...
  2. 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...
  3. 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...
  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. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency ..
  5. 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
    Current factor VIII (FVIII) products display a half-life (t(1/2)) of ∼ 8-12 hours, requiring frequent intravenous injections for prophylaxis and treatment of patients with hemophilia A...
  6. 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 (..
  7. ncbi Purification and characterization of a new recombinant factor VIII (N8)
    L Thim
    Biopharmaceutical Research Unit, Novo Nordisk A S, Maaloev, Denmark
    Haemophilia 16:349-59. 2010
    A new recombinant factor VIII (FVIII), N8, has been produced in Chinese hamster ovary (CHO) cells. The molecule consists of a heavy chain of 88 kDa including a 21 amino acid residue truncated B-domain and a light chain of 79 kDa...
  8. ncbi Factor VIII and von Willebrand factor interaction: biological, clinical and therapeutic importance
    V Terraube
    Haemostasis Research Group, Institute of Molecular Medicine, Trinity College, Dublin, Ireland
    Haemophilia 16:3-13. 2010
    The interaction of factor VIII (FVIII) with von Willebrand Factor (VWF) is of direct clinical significance in the diagnosis and treatment of patients with haemophilia A and von Willebrand disease (VWD)...
  9. ncbi Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia
    John A Livesey
    Imperial College School of Medicine, Imperial College, London, UK
    Thorax 67:328-33. 2012
    Elevated plasma levels of coagulation factor VIII are a strong risk factor for pulmonary emboli and deep venous thromboses.
  10. 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
    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...
  11. ncbi Distribution of Th1- and Th2-induced anti-factor VIII IgG subclasses in congenital and acquired hemophilia patients
    Mark T Reding
    Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis St Paul, MN, USA
    Thromb Haemost 88:568-75. 2002
    Development of antibodies (Ab) that inhibit the procoagulant function of factor VIII (fVIII) seriously complicates the treatment of hemophilia A patients. It also causes acquired hemophilia, a rare yet serious autoimmune disease...
  12. pmc Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant
    Jenny McIntosh
    University College London Cancer Institute, London, United Kingdom
    Blood 121:3335-44. 2013
    Recombinant adeno-associated virus (rAAV) vectors encoding human factor VIII (hFVIII) were systematically evaluated for hemophilia A (HA) gene therapy. A 5...
  13. 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
    Human coagulation factor VIII (fVIII) is inefficiently biosynthesized in vitro and has proven difficult to express at therapeutic levels using available clinical gene-transfer technologies...
  14. 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
    ..data reporting incidence or prevalence of inhibitors in patients with haemophilia A, and prospective studies of factor VIII (FVIII) in the treatment of previously untreated patients which reported the development of inhibitors as an ..
  15. ncbi Expression of active human factor VIII from recombinant DNA clones
    W I Wood
    Nature 312:330-7. 1984
    DNA clones encoding the complete 2,351 amino acid sequence for human factor VIII have been isolated and used to produce biologically active factor VIII in cultured mammalian cells...
  16. 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...
  17. ncbi Factor VIII inhibitors: a 50-year perspective
    D Green
    Division of Hematology Oncology, Department of Medicine, Feinberg School of Medicine of Northwestern University, Chicago, IL 60611, USA
    Haemophilia 17:831-8. 2011
    Inhibitors of factor VIII (FVIII) have been studied for more than 50 years, but diagnostic and therapeutic challenges remain...
  18. ncbi Influence of phospholipids on the assessment of factor VIII activity
    M Mikaelsson
    Recombinant Factor VIII, R and D, Pharmacia and Upjohn AB, Stockholm, Sweden
    Haemophilia 4:646-50. 1998
    In view of reported discrepancies between different factor VIII assays, the influence of phospholipids on the performance of one-stage clotting (OS) and chromogenic substrate (CS) assays was evaluated...
  19. ncbi Clearance mechanisms of von Willebrand factor and factor VIII
    P J Lenting
    Department of Clinical Chemistry and Haematology, Laboratory for Thrombosis and Haemostasis, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
    J Thromb Haemost 5:1353-60. 2007
  20. 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...
  21. ncbi A Mr 46,000 human milk fat globule protein that is highly expressed in human breast tumors contains factor VIII-like domains
    D Larocca
    John Muir Cancer and Aging Research Institute, Walnut Creek, California 94596
    Cancer Res 51:4994-8. 1991
    ..Sequence analysis revealed strong homology of the Mr 46,000 glycoprotein with serum factors VIII and V, in the region implicated in phospholipid binding...
  22. 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
    Haemophilia A (HA) is an X-linked bleeding disorder caused by diverse mutations in the human coagulation factor VIII (FVIII) gene. We have analysed DNA from 109 unrelated Indian patients with HA for their FVIII gene defects...
  23. ncbi Structural and functional characterization of B-domain deleted recombinant factor VIII
    H Sandberg
    Pharmacia AB, Stockholm, Sweden
    Semin Hematol 38:4-12. 2001
    A new high-purity recombinant factor VIII preparation has been developed for the treatment of hemophilia A...
  24. ncbi The life cycle of coagulation factor VIII in view of its structure and function
    P J Lenting
    Departments of Plasma Protein Technology and Blood Coagulation, CLB, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands
    Blood 92:3983-96. 1998
  25. 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...
  26. 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
    In this study, we describe a flow cytometry (FC) system for detecting antibodies to factor VIII (FVIII) and compare its results with those of enzyme-linked immunosorbent assay (ELISA) that detects both inhibitory (I-Ab) and non-..
  27. 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)...
  28. ncbi von Willebrand factor and its propeptide: the influence of secretion and clearance on protein levels and the risk of venous thrombosis
    A Y Nossent
    Hematology, Hemostasis and Thrombosis Research Center, Leiden University Medical Center, Leiden, The Netherlands
    J Thromb Haemost 4:2556-62. 2006
    ..VWF is secreted in equimolar amounts with its propeptide, which has a shorter half-life. VWF propeptide can be used as a measure of VWF secretion and allows estimation of the VWF half-life...
  29. ncbi Microvessel densities and microvascular architecture in colorectal carcinomas and their liver metastases: significant correlation of high microvessel densities with better survival
    F Prall
    Department of Pathology, University of Rostock, Germany
    Histopathology 42:482-91. 2003
    ..Microvessel densities in cancers have been shown to be a prognostic factor for some types of cancer. For colorectal cancer, however, the situation is far from clear...
  30. 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 aim of this study was to evaluate the in vitro function of the new recombinant factor VIII (FVIII) compound, N8...
  31. 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
    b>Factor VIII inhibitors are IgG alloantibodies that arise during replacement therapy in 25 to 50 percent of patients with severe hemophilia A...
  32. 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
    ..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 FVIII in HA patients...
  33. 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
    The spontaneous formation of neutralizing antibodies (inhibitors) to factor VIII (FVIII) in patients with cancer is a well known phenomenon...
  34. 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
    Production of recombinant B-domain-deleted canine factor VIII (cFVIII-BDD) unexpectedly revealed superior protein yields with 3-fold increased specific activity relative to human FVIII-BDD (hFVIII-BDD)...
  35. pmc Bioengineering of coagulation factor VIII for efficient expression through elimination of a dispensable disulfide loop
    S R Selvaraj
    Department of Pediatrics and Communicable Diseases, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    J Thromb Haemost 10:107-15. 2012
    Heterologous expression of factor VIII (FVIII) is about two to three orders of magnitude lower than similarly sized proteins...
  36. 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...
  37. ncbi Expression of recombinant human factor VIII in milk of several generations of transgenic rabbits
    Peter Chrenek
    Slovak Agricultural Research Centre, Nitra, Slovak Republic
    Transgenic Res 16:353-61. 2007
    ..5 kb murine whey acidic protein promoter (mWAP), 7.2 kb of the human clotting factor VIII (hFVIII) cDNA and 4.6 kb of 3' flanking sequences of mWAP gene were crossed for three generations...
  38. 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
    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...
  39. 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...
  40. ncbi Expression of active human blood clotting factor VIII in mammary gland of transgenic rabbits
    L Hiripi
    Institute of Animal Biology, Agricultural Biotechnology Center, Godollo, Hungary
    DNA Cell Biol 22:41-5. 2003
    Human clotting factor VIII is probably the largest protein to be expressed to date in the mammary gland of a transgenic animal, and it requires extensive posttranslational modification to achieve full biological activity...
  41. 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
    Hemophilia A, a deficiency of functional coagulation factor VIII (FVIII), is treated via protein replacement therapy...
  42. 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
    ..Although deficiencies of factor VIII (haemophilia A) and factor IX (haemophilia B) are well recognised, von Willebrand's disease is much more common...
  43. ncbi An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis
    Armando Tripodi
    Department of Internal Medicine and Medical Specialties, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy
    Gastroenterology 137:2105-11. 2009
    ..We investigated whether plasma from cirrhotic patients has an imbalance of pro- vs anti-coagulation factors...
  44. ncbi LMAN1 and MCFD2 form a cargo receptor complex and interact with coagulation factor VIII in the early secretory pathway
    Bin Zhang
    Life Sciences Institute, the Departments of Biological Chemistry, Internal Medicine, Human Genetics Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 280:25881-6. 2005
    ..and MCFD2 are the causes of a human genetic disorder, combined deficiency of coagulation factor V and factor VIII. LMAN1 is a type 1 transmembrane protein with homology to mannose-binding lectins...
  45. 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...
  46. 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
    b>Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation. Quantitative or qualitative deficiencies of FVIII result in the inherited bleeding disorder hemophilia A...
  47. 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
    It has been suggested that plasma-derived factor VIII products induce fewer inhibitors than recombinant factor VIII products...
  48. 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...
  49. ncbi Sulfation of Tyr1680 of human blood coagulation factor VIII is essential for the interaction of factor VIII with von Willebrand factor
    A Leyte
    Department of Blood Coagulation, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam
    J Biol Chem 266:740-6. 1991
    The acidic region of the Factor VIII light chain was studied with regard to structural requirements for the formation of a functional von Willebrand factor (vWF)-binding site...
  50. 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
    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...
  51. 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...
  52. ncbi A multicenter pharmacokinetic study of the B-domain deleted recombinant factor VIII concentrate using different assays and standards
    M Morfini
    Hematology Department and Hemophilia Center, University Hospital of Florence, Italy
    J Thromb Haemost 1:2283-9. 2003
    ....
  53. ncbi Analysis of mRNA in hemophilia A patients with undetectable mutations reveals normal splicing in the factor VIII gene
    O El-Maarri
    Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany
    J Thromb Haemost 3:332-9. 2005
    haemophilia A (HA) is characterized by partial or total deficiency of factor VIII (FVIII) protein activity. It is caused by a broad spectrum of mutations in the FVIII gene...
  54. ncbi Upper extremity compartment syndrome secondary to acquired factor VIII inhibitor. A case report
    Asif M Ilyas
    Department of Orthopaedic Surgery and Sports Medicine, Temple University Hospital, Outpatient Building 6th Floor, 3401 North Broad Street, Philadelphia, PA 19140, USA
    J Bone Joint Surg Am 87:1606-8. 2005
  55. 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...
  56. 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
    High-capacity adenoviral (HC-Ad) vectors expressing B-domain-deleted human or canine factor VIII from different liver-specific promoters were evaluated for gene therapy of hemophilia A...
  57. 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...
  58. 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...
  59. ncbi ATP-dependent dissociation of non-disulfide-linked aggregates of coagulation factor VIII is a rate-limiting step for secretion
    L Tagliavacca
    Department of Biological Chemistry and Howard Hughes Medical Institute, 1150 West Medical Center Drive, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Biochemistry 39:1973-81. 2000
    Deficiency in coagulation factor VIII leads to the bleeding disorder hemophilia A. Previous studies demonstrated that factor VIII secretion is limited due to an ATP-requiring step early in the secretory pathway...
  60. pmc Coexpression of factor VIII heavy and light chain adeno-associated viral vectors produces biologically active protein
    M Burton
    Avigen Inc, 1201 Harbor Bay Parkway, Alameda, CA 94502, USA
    Proc Natl Acad Sci U S A 96:12725-30. 1999
    ..This suggests that coexpression of the heavy and light chains of hFVIII may be a feasible approach for treatment of hemophilia A...
  61. 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...
  62. ncbi Pharmacokinetics and safety of OBI-1, a recombinant B domain-deleted porcine factor VIII, in subjects with haemophilia A
    C L Kempton
    Aflac Cancer Center and Blood Disorders Service and Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
    Haemophilia 18:798-804. 2012
    OBI-1 is a recombinant B-domain deleted porcine factor VIII (FVIII)...
  63. ncbi Elevated factor VIII levels and risk of venous thrombosis
    P Vince Jenkins
    Haemostasis Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James s Hospital, Trinity College Dublin, Dublin, Ireland
    Br J Haematol 157:653-63. 2012
    ..In contrast, an increasing body of work supports the hypothesis that increased plasma factor VIII (FVIII) levels may be important in this context...
  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. pmc Effect of HLA DR epitope de-immunization of Factor VIII in vitro and in vivo
    Leonard Moise
    EpiVax, Inc, Providence, RI 02903, USA
    Clin Immunol 142:320-31. 2012
    T cell-dependent development of anti-Factor VIII (FVIII) antibodies that neutralize FVIII activity is a major obstacle to replacement therapy in hemophilia A...
  66. ncbi Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A
    L Bi
    Nat Genet 10:119-21. 1995
    ..X-linked disease which affects 1 in 5-10,000 males in all populations and is caused by defects in coagulation factor VIII. Roughly 60% of patients have severe disease with factor VIII activity < 1% of normal; they have frequent ..
  67. ncbi Characterisation of the post-translational modifications of a novel, human cell line-derived recombinant human factor VIII
    Christoph Kannicht
    Octapharma, Berlin, Molecular Biochemistry, Germany
    Thromb Res 131:78-88. 2013
    ..rhFVIII expression in a human cell line avoids expression of undesirable mammalian glycoforms like Galα1-3Galβ1-GlcNAc-R (α-Gal) and N-glycolylneuraminic acid (Neu5Gc), which constitute epitopes antigenic to humans...
  68. pmc cDNA cloning of a mouse mammary epithelial cell surface protein reveals the existence of epidermal growth factor-like domains linked to factor VIII-like sequences
    J D Stubbs
    Cell and Molecular Biology Division, Lawrence Berkeley Laboratory, University of California, Berkeley 94720
    Proc Natl Acad Sci U S A 87:8417-21. 1990
    ..mRNA expression was detectable in mammary tissue from nonpregnant animals but was maximal in the lactating gland. In cultured cells, mRNA levels also correlated with the degree of cellular differentiation...
  69. pmc Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype
    Joshua I Siner
    Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 121:4396-403. 2013
    Recombinant canine B-domain deleted (BDD) factor VIII (FVIII) is predominantly expressed as a single-chain protein and exhibits greater stability after activation compared with human FVIII-BDD...
  70. ncbi Kinetic parameters of monoclonal antibodies ESH2, ESH4, ESH5, and ESH8 on coagulation factor VIII and their influence on factor VIII activity
    C Egler
    Center of Advanced European Studies and Research, Bonn, Germany
    J Mol Recognit 22:301-6. 2009
    ..ESH2, ESH4, ESH5, and ESH8 specifically bind and inhibit the procoagulant activity of human coagulation factor VIII (FVIII)...
  71. ncbi Human parvovirus B19 infection in hemophiliacs first infused with two high-purity, virally attenuated factor VIII concentrates
    A Azzi
    Institute of Microbiology, University of Florence, Italy
    Am J Hematol 39:228-30. 1992
    ..groups of susceptible (anti-B19 negative) hemophiliacs infused with high-purity, heated (pasteurized) or solvent-detergent-treated factor VIII concentrates. Both products infected a relatively high proportion of patients (nine of 20).
  72. ncbi Patient and parent preferences for haemophilia A treatments
    A F Mohamed
    RTI International, Research Triangle Park, NC 27709 2194, USA
    Haemophilia 17:209-14. 2011
    Little is known about the relative importance of factor VIII (FVIII) treatment attributes to haemophilia A patients and their willingness to accept trade-offs among these attributes...
  73. ncbi Acquired factor VIII inhibitors in oncohematology: a systematic review
    Massimo Franchini
    Servizio di Immunoematologia e Trasfusione Centro Emofilia, Azienda Ospedaliera di Verona, Ospedale Policlinico, and Dipartimento di Scienze Biomediche e Chirurgiche, Universita di Verona, Piazzale Ludovico Scuro, 37134 Verona, Italy
    Crit Rev Oncol Hematol 66:194-9. 2008
    ..but potentially life-threatening hemorrhagic disorder caused by the onset of autoantibodies against coagulation factor VIII. Acquired hemophilia A is most frequently associated with autoimmune diseases, neoplasia, pregnancy and drug ..
  74. 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
    The development of antibodies (Abs) against infused factor VIII (FVIII) is currently one of the most serious complications in the treatment of patients suffering from haemophilia A...
  75. ncbi Absence of correlation between X chromosome inactivation pattern and plasma concentration of factor VIII and factor IX in carriers of haemophilia A and B
    K H Orstavik
    Department of Medical Genetics, Ulleval University Hospital, Oslo, Norway
    Thromb Haemost 83:433-7. 2000
    Haemophilia A and B are X-linked disorders which are due to a reduced activity of coagulation factor VIII or IX, respectively...
  76. ncbi Cell surface heparan sulfate proteoglycans participate in factor VIII catabolism mediated by low density lipoprotein receptor-related protein
    A G Sarafanov
    Holland Laboratory, American Red Cross, Rockville, Maryland 20855, George Washington University, Washington D.C. 20037, USA
    J Biol Chem 276:11970-9. 2001
    We have demonstrated previously that catabolism of a coagulation factor VIII (fVIII) from its complex with von Willebrand factor (vWf) is mediated by low density lipoprotein receptor-related protein (LRP) (Saenko, E. L., Yakhyaev, A. V...
  77. 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
    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...
  78. pmc Peak thrombin generation and subsequent venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE) study
    P L Lutsey
    Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55454, USA
    J Thromb Haemost 7:1639-48. 2009
    ..Thrombin is an enzyme that is essential for the acceleration of the coagulation cascade and the conversion of fibrinogen to clottable fibrin...
  79. ncbi The acidic region of the factor VIII light chain and the C2 domain together form the high affinity binding site for von willebrand factor
    E L Saenko
    Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA
    J Biol Chem 272:18007-14. 1997
    ..factor (vWf) was previously localized to the carboxyl terminus of the C2 domain of the light chain (LCh) of factor VIII (fVIII). The acidic region of the LCh, residues 1649-1689, also controls fVIII...
  80. 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...
  81. ncbi Mutagenesis of a potential immunoglobulin-binding protein-binding site enhances secretion of coagulation factor VIII
    M Swaroop
    Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    J Biol Chem 272:24121-4. 1997
    Coagulation factor VIII (FVIII) and factor V are homologous glycoproteins that have a domain structure of A1-A2-B-A3-C1-C2...
  82. pmc Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium
    Nicholas L Smith
    Department of Epidemiology, University of Washington, Seattle, Wash 98101, USA
    Circulation 121:1382-92. 2010
    ..Plasma levels of coagulation factors VII (FVII), VIII (FVIII), and von Willebrand factor (vWF) influence risk of hemorrhage and thrombosis. We conducted genome-wide association studies to identify new loci associated with plasma levels...
  83. 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
    ..Screening of the factor VIII gene (FVIII) was performed using denaturing high-performance liquid chromatography (DHPLC) and direct ..
  84. 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
    Injected factor VIII (FVIII), the current treatment for haemophilia A, leads to major improvements in the quality of life and life expectancy of individuals with this disorder...
  85. pmc Enhanced biosynthesis of coagulation factor VIII through diminished engagement of the unfolded protein response
    Harrison C Brown
    Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service, Emory University School of Medicine and Children s Healthcare of Atlanta, Atlanta, Georgia 30322, USA
    J Biol Chem 286:24451-7. 2011
    Human and porcine coagulation factor VIII (fVIII) display a biosynthetic efficiency differential that is being exploited for the development of new protein and gene transfer-based therapies for hemophilia A...
  86. ncbi Acquired factor VIII inhibitors in pregnancy: data from the Italian Haemophilia Register relevant to clinical practice
    Francesco Baudo
    Thrombosis and Hemostasis Unit, Nigurda Hospital, Milan, Italy
    BJOG 110:311-4. 2003
    To review the clinical problems related to the inhibitor of factor VIII (FVIII) in pregnancy.
  87. 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
    The development and introduction of recombinant factor VIII (rFVIII) concentrates nearly 20 years ago represented a major advance in the treatment of hemophilia A patients...
  88. ncbi An improved manufacturing process for Xyntha/ReFacto AF
    B Kelley
    Process Development, Genentech, Inc, 1 DNA Way, South San Francisco, CA, USA
    Haemophilia 16:717-25. 2010
    ..The product produced by the improved manufacturing process is named Xyntha/ReFacto AF...
  89. 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
    Causative mutations in the factor VIII gene of seven unrelated patients with severe haemophilia A were identified using the mutation screening procedure conformation sensitive gel electrophoresis (1) and characterised by direct ..
  90. 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. This bleeding disorder can be treated with Factor VIII replacement therapy, but close to a third of patients will be immunized to the treatment and begin to form ..
  91. ncbi High level expression of recombinant porcine coagulation factor VIII
    Christopher B Doering
    Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA
    J Biol Chem 277:38345-9. 2002
    Recombinant human factor VIII expression levels, in vitro and in vivo, are significantly lower than levels obtained for other recombinant coagulation proteins...
  92. 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
    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...
  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
    ..Porcine FVIII is a potentially useful therapeutic agent because of its low crossreactivity with many inhibitors. Recombinant porcine FVIII (rpFVIII) is undergoing clinical trials in inhibitor patients...
  94. 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...
  95. 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
  96. 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
    ..In particular, antibodies that neutralize infused factor VIII or IX (high-responding inhibitors) make treatment responses, and thereby costs, much less predictable...
  97. 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
    Mutations in LMAN1 (ERGIC-53) or MCFD2 cause combined deficiency of factor V and factor VIII (F5F8D)...
  98. ncbi Anti-factor VIII antibodies: a 2005 update
    Géraldine Lavigne-Lissalde
    CNRS UMR 5160, Centre de Pharmacologie et Biotechnologie pour la Santé, Faculte de Pharmacie, Montpellier, France
    Thromb Haemost 94:760-9. 2005
    The development of anti-factor VIII (FVIII) antibodies is currently one of the most serious complications in the treatment of haemophilia A patients...
  99. 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
    ..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...
  100. 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
    We reported total correction of blood coagulation plasma factor VIII (FVIII) activity, using adeno-associated virus serotype 8 (AAV8) vectors for liver-specific gene transfer in hemophilia A mice...
  101. ncbi Enhanced production of recombinant B-domain deleted factor VIII from Chinese hamster ovary cells by propionic and butyric acids
    Bok Hwan Chun
    Department of Agricultural Chemistry, College of Life and Environmental Sciences, Korea University, 5 Ga Anamdong, Sungbook gu, Seoul 136 075, Korea
    Biotechnol Lett 25:315-9. 2003
    Sodium propionate, as well as sodium butyrate, enhanced the production of recombinant B-domain-deleted, factor VIII (rFVIIIdB) by Chinese hamster ovary cells growing in a spinner-flask with a protein-free medium by more than six-fold...

Research Grants67

  1. CFI Pathogen Inactivation Technology
    Trevor P Castor; Fiscal Year: 2010
    ..g., Factor VIII) integrity;(2) test prototypical and emerging viruses and bacteria in human plasma in extant SFS-CFI units and ..
  2. Regulation of factor VIII Levels and Activity by Members of LDL Receptor Family
    Dudley K Strickland; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Factor VIII (fVIII) and factor IX (fIX) are two key plasma proteins that are deficient in the bleeding disorders Hemophilia A and Hemophilia B, respectively...
  3. Mechanisms of Race-Based Differences in Factor VIII Immunogenicity in Hemophilia
    KATHLEEN PALMER PRATT; Fiscal Year: 2010
    ..provided by applicant): The proposed study 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" (..
  4. Platelet-Derived FVIII Gene Therapy of Hemophilia A
    Qizhen Shi; Fiscal Year: 2013
    ..is the most common severe bleeding disorder resulting from hereditary deficiency of the blood clotting protein, factor VIII (FVIII)...
  5. Phase 2a Study of Ataluren in Hemophilia A and B (IND 104,321)
    JAY A BARTH; Fiscal Year: 2010
    ..90 power whether PTC124 provides pharmacological effect in HA/HB as measured by plasma clotting factor VIII (FVIII)/FIX activity...
  6. A Novel Therapy for Septic Shock
    Xiaoling Qiang; Fiscal Year: 2011
    ..Recent evidence shows that the opsonizing protein milk fat globule epidermal growth factor-factor VIII (MFG-E8) is involved in apoptotic cell clearance...
  7. Hematopoietic gene therapy for hemophilia A
    H Trent Spencer; Fiscal Year: 2013
    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...
  8. Reasons for Racial Disparities in Venous Thromboembolism
    NEIL ADRIAN ZAKAI; Fiscal Year: 2010
    ..Results will lead to a follow- up proposal to obtain funding to evaluate novel biomarkers of VTE risk such as factor VIII, von Willebrand factor levels, and genetic factors in African-Americans versus European-Americans...
  9. Membrane Receptors Regulating Megakaryocyte Endocytosis of Factor V from Plasma
    BETH BOUCHARD; Fiscal Year: 2012
    ..In other studies, the ability of factor VIII, a protein highly homologous to factor V whose clearence is mediated by LRP-1, to interact with this receptor ..
  10. Therapeutic-Expression of a Platelet-Specific Integrin
    DAVID ALLEN WILCOX; Fiscal Year: 2010
    ..be used to explore strategies to correct canine Hemophilia A via targeted synthesis and storage of coagulation factor VIII to platelet a-granules...
  11. Sepsis and Mediators: the Role of MFG-E8
    Ping Wang; Fiscal Year: 2010
    ..Recent evidence showed that the opsonizing protein milk fat globule epidermal growth factor- factor VIII (MFG-E8) is involved in apoptotic cell clearance...
  12. 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...
  13. In vivo lentiviral transduction of bone marrow cells for hemophilia gene therapy
    Carol H Miao; Fiscal Year: 2013
    ..gene therapy strategy to treat hemophilia A (HemA) by directly transferring lentiviral vectors encoding factor VIII (FVIII) gene into bone marrow cells...
  14. Molecular Genetic Study of von Willebrand Factor
    David Ginsburg; Fiscal Year: 2013
    ..In contrast, elevated levels of VWF and the associated protein, factor VIII, are a major risk factor for thrombosis...
  15. RAMP Mediated Gene Delivery
    Kevin G Rice; Fiscal Year: 2012
    ..RAMP polyplexes will be used to treat Factor VIII deficiency in hemophilic mice...
  16. Induction of Tolerance to Factor VIII in Hemophilia
    DAVID WILLIAM SCOTT; Fiscal Year: 2012
    Hemophilia A is an X-linked disorder in which clotting factor VIII (fVIII) mutations lead to a loss of fVIII expression and serious bleeding...
  17. Structure and Stability Studies of Factor VIII to Overcome the Immune Response
    PAUL CLINTON SPIEGEL; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Blood coagulation factor VIII is a non-enzymatic glycoprotein cofactor that is essential for proper regulation of the blood coagulation cascade...
  18. Bioengineered factor VIII gene therapy for hemophilia A
    H Trent Spencer; Fiscal Year: 2012
    ..studies, we have shown that the transplantation of genetically-engineered hematopoietic stem cells can restore factor VIII (fVIII) activity to curative levels in hemophilia A mice and that human hematopoietic stem cells are readily ..
  19. MOLECULAR GENETICS OF COAGULATION DISORDERS
    David Ginsburg; Fiscal Year: 2013
    ..genes for thrombotic thrombocytopenic purpura (TTP);(2) continue to explore the critical factors that limit factor VIII expression...
  20. Blocking the immune response to Helper-dependent adenovirus vector for Hemophilia
    Masataka Suzuki; Fiscal Year: 2011
    ..Project Abstract. Hemophilia A (HA) is a common disorder of coagulation caused by deficiency of factor VIII (FVIII). The mainstay of treatment has been replacement therapy with recombinant human FVIII...
  21. Development of a novel production platform for complex recombinant biotherapeutic
    JOHN S LOLLAR; Fiscal Year: 2012
    ..Of the recombinant proteins currently marketed, coagulation factor VIII is manufactured with the lowest efficiency and is by far the most expensive on a per unit mass basis...
  22. Von Willebrand Factor Multimer Assembly and Structure
    J Evan Sadler; Fiscal Year: 2012
    ..b>Factor VIII can be stored with VWF in Weibel-Palade bodies, and these studies will also demonstrate how factor VIII affects ..
  23. STRUCTURE AND REGULATION OF HUMAN FACTOR VIII
    Philip J Fay; Fiscal Year: 2013
    ..A, the most common of the severe, inherited bleeding disorders, results from a deficiency or defect in factor VIII. We propose to define critical aspects of factor VIII structure and regulation that includes fine point details ..
  24. Hemophilia Adult Prophylaxis Study
    MARGARET VICTORIA RAGNI; Fiscal Year: 2012
    ..the feasibility of conducting a Phase III randomized clinical trial comparing two doses of recombinant factor VIII (r.FVIII) prophylaxis in adults with severe hemophilia A...
  25. Mechanisms of Immunogenicity of Factor VIII
    Shannon L Meeks; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Inhibitory antibodies to factor VIII (fVIII) develop in approximately 30% of patients with severe hemophilia A in response to infusions of fVIII...
  26. Blocking the immune response to HDAd for Hemophilia A gene therapy
    Masataka Suzuki; Fiscal Year: 2013
    ..Project Abstract. Hemophilia A (HA) is a common disorder of coagulation caused by deficiency of factor VIII (FVIII). The mainstay of treatment has been replacement therapy with recombinant human FVIII...
  27. In vivo function and tolerance to Factor VIII variants
    BRENDAN HL LEE; Fiscal Year: 2011
    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...
  28. 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...
  29. FIV Vectors for the Treatment of Hemophilia A
    William C Raschke; Fiscal Year: 2012
    ..The lack of sufficient expression levels Factor VIII (FVIII) in hemophilic patients indicates that further improvements of the current gene delivery systems are ..
  30. Transplantation of Genetically Modified, Immune-privileged Steroli Cells
    Jannette M Dufour; Fiscal Year: 2012
    ..There are many disorders that have the potential to be treated by gene therapy;for example, delivery of factor VIII for the treatment of hemophilia. However, an efficient and safe delivery system has not yet been developed...
  31. Combined Factor VIII Replacement and Tolerance Therapy for Hemophilia A
    ANNE SEARLS DEGROOT; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The goal of this new SBIR program is to produce a combined clotting Factor VIII replacement and immunomodulatory therapy that will provide FVIII-specific tolerance induction at therapeutic doses for ..
  32. Chemistry and Biology of Coagulation
    Sriram Krishnaswamy; Fiscal Year: 2013
    ..coagulation and von Willebrand Factor processing by investigating the regulation of ADAMTS13 function by factor VIII and shear stress...
  33. 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...
  34. AAV-Mediated Gene Therapy for Hemophilia
    Andrew M Davidoff; Fiscal Year: 2013
    ..virus (AAV) vectors can safely mediate long-term expression of therapeutic levels of coagulation factor VIII (FVIII) for the treatment of hemophilia A...
  35. Epitope-driven deimmunization of Factor VIII
    ANNE SEARLS DE GROOT; Fiscal Year: 2010
    Hemophilia A patients are prone to develop inhibitory immune responses to the very therapy they require: Factor VIII protein replacement...
  36. VWF Multimer Distribution a Phenotypic Modifier of Hemophilia A
    CHAR MARIE WITMER; Fiscal Year: 2013
    ..severe (<1%), moderate (1-5%) and mild (5-30%), but it is well described that 10-15% of patients with severe factor VIII deficiency have a "mild" bleeding phenotype...
  37. Functional Implications of VWF A1 Domain Polymorphisms
    Veronica H Flood; Fiscal Year: 2013
    ..In addition, the role of factor VIII (FVIII) release following VWF-platelet binding will be investigated...
  38. ER-to-Golgi transport of coagulation factors V and VIII
    Bin Zhang; Fiscal Year: 2013
    Description (provided by the applicant): Coagulation factors V (FV) and factor VIII (FVIII) are both secreted glycoproteins that share pivotal roles in both hemostasis and thrombosis...
  39. Development and Pharmacology of Novel Lipidic rAHF
    SATHY VENKAT BALU-IYER; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The development of antibody responses against therapeutic proteins such as Factor VIII (FVIII) is a major clinical complication that compromises the safety and efficacy of protein based therapeutics...
  40. Prevention of the Complications of Bleeding Disorders Through HTCS
    Regina Butler; Fiscal Year: 2010
    ..by applicant): Hemophilia is an inherited bleeding disorder resulting from a deficiency of coagulation factor VIII or factor IX and von Willebrand Disease (VWD) is an inherited bleeding disorder resulting from decreased or ..
  41. Glycomics of Heart and Lung Disease in the Genomic Era
    Muredach P Reilly; Fiscal Year: 2013
    ..as well as multiple cardiopulmonary biomarkers traits such as circulating levels of VonWillebrand factor (VWF), Factor VIII, soluble ICAM-1, soluble E-selectin, and LDL cholesterol...
  42. Genetic Epidemiological Study of Venous Thromboembolism and Hemostatic Factors
    Weihong Tang; Fiscal Year: 2012
    ....
  43. Manufacturing Process Development for Bioengineered FVIII
    JOHN S LOLLAR; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The manufacturing of recombinant coagulation factor VIII is a complex, labor and capital intensive endeavor...
  44. Natural Variation in VWF and FVIII
    JILL MARIE JOHNSEN; Fiscal Year: 2013
    ..provided by applicant): Levels of the critical plasma clotting proteins von Willebrand Factor (VWF) and Factor VIII (FVIII) are widely variable in humans...
  45. Immunology of Factor IX Gene Transfer to Liver
    Roland W Herzog; Fiscal Year: 2013
    ..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...
  46. Gene Therapy for hemophilia using muscle-expressed FVIIa
    Katherine A High; Fiscal Year: 2011
    ..This approach has immunological advantages over Factor IX (FIX) or Factor VIII (FVIII) gene strategies since the recipient is tolerant to the transgene...
  47. TISSUE AND SERUM INDICATORS OF LUNG CANCER RECURRENCE
    David Harpole; Fiscal Year: 2000
    ..genetic markers (Kras, erbB-1, erbB-2, rb, p53, bcl-2), markers of metastatic propensity (angiogenesis factor viii), proliferation markers (K1-67) and markers of cellular differentiation (Blood group A, H/LeV/LeB, NCAM, CD44)...
  48. 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...
  49. Inhibitor development in patients with hemophilia A undergoing surgery
    CHRISTINE LUISE KEMPTON; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The development of neutralizing anti-factor VIII (fVIII) antibodies, inhibitors, is the most significant complication affecting treated patients with hemophilia A (HA)...
  50. Structural studies of blood coagulation proteins
    Barry Stoddard; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): Factor VIII (fVIII) is a serum protein that acts as a critical cofactor and regulator of the intrinsic blood coagulation pathway...
  51. Patient-Level Meta-analysis: Effect of age of initiation, intensity and duration
    Marilyn J Manco-Johnson; Fiscal Year: 2013
    ..Effects of age of initiation, duration of therapy and intensity of treatment (dosing schedule) with factor VIII prophylaxis on prevention of hemophilic arthropathy using joint scoring via sensitive and specific magnetic ..
  52. Molecular engineering of factor VIII gene for rAAV delivery
    Weidong Xiao; Fiscal Year: 2012
    ..This disease is primarily caused by deficiency in the factor VIII gene located in the X-chromosome and is difficult to treat by conventional medicine...
  53. rhMFG-E8 for Alcohol-induced Tissue Injury and Infections (TheraSource, LLC)
    Wayne Chaung; Fiscal Year: 2013
    ..Milk fat globule epidermal growth factor-factor VIII (MFG-E8) is involved in the clearance of apoptotic cells...
  54. Gene Therapy for the Hemophilias
    Christopher Walsh; Fiscal Year: 2006
    ..A major obstacle in the application of rAAV in gene therapy for hemophilia A (factor VIII deficiency) is the conflict of the limited packaging capacity of rAAV and the large size of the human FVIII ..
  55. FUNCTION OF FACTOR VIII ON THE PLATELET MEMBRANE
    Gary Gilbert; Fiscal Year: 2001
    ..yrs we have found that on membranes with low mole fractions of acidic phospholipid, resembling cell membranes, factor VIII exhibits stereoselective affinity for phosphatidyl-L-serine containing binding sites...
  56. BASIC AND CLINICAL STUDIES OF COAGULATION PROTEINS
    Charles Francis; Fiscal Year: 2003
    ..Dr. Fay's project will continue detailed studies of factor VIII interactions in the intrinsic tenase complex...
  57. Stem cell gene therapy for canine hemophilia
    Friedrich Schuening; Fiscal Year: 2002
    Hemophilia can potentially be cured by ex vivo retrovirus-mediated transfer of the factor VIII or factor IX gene into autologous hematopoietic stem cells followed by infusion of the genetically corrected cells into the stem cell donor...
  58. DDAVP IN CONGENITAL PLATELET FUNCTION DISORDERS
    A Rao; Fiscal Year: 1990
    ..on the bleeding time, platelet counts, platelet volume, in vitro platelet function, and plasma levels of factor VIII activity, factor VIII-related antigen, factor VIII-von Willebrand factor/ristocetin cofactor activity and ..
  59. EPITOPES OF ANTIFACTOR VIII ANTIBODIES IN HEMOPHILIACS
    Dorothea Scandella; Fiscal Year: 1999
    ..a new proposal which is a logical extension of the PI's past work describing clinically important antibodies to factor VIII in hemophiliacs...
  60. Hemophilia A: Intrathymic Delivery for Tolerance and Longterm Expression of FVIII
    William Raschke; Fiscal Year: 2007
    ..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...
  61. PROTEOLYTIC ANTIBODIES FOR TREATMENT OF PSORIASIS
    ROBERT BALINT; Fiscal Year: 2009
    ..For example, Factor VIII hydrolysis by proteolytic antibodies accounts for Factor VIII resistance in many hemophiliacs...
  62. In Utero Stem Cell Transplantation for Hemophilia A
    Graca Almeida Porada; Fiscal Year: 2006
    ..by applicant): Hemophilia A is an X-linked recessive bleeding disorder caused by the deficiency/abnormality of Factor VIII. Currently, treatment of hemophilia involves factor replacement using fresh frozen plasma, cryoprecipitate, or ..
  63. CONTROL OF COAGULATION
    WHYTE OWEN; Fiscal Year: 1990
    ..b>Factor VIII has been purified and its gene has been cloned...
  64. GENETICS OF INHIBITOR FORMATION IN HEMOPHILIA
    Joan Gill; Fiscal Year: 2001
    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...
  65. ANALYSIS OF FACTOR VIII COAGULANT ANTIGEN
    Mark Weinstein; Fiscal Year: 1990
    Abnormalities of factor VIII and/or von Willebrand factor (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, ..
  66. Repair of Factor VIII by targeted RNA trans splicing
    S Mansfield; Fiscal Year: 2003
    ..Hemophilia A is caused by deficiency of coagulation factor VIII (FVIII) and is a prime disorder for genetic correction...
  67. Repair of Factor VIII by targeted RNA trans-splicing
    S Mansfield; Fiscal Year: 2006
    ..Hemophilia A is caused by deficiency of coagulation factor VIII (FVIII) and is a prime disorder for genetic correction...