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Your search keyword '"White, Gilbert C."' showing total 25 results
Start Over Author "White, Gilbert C." Topic factor viii
25 results on '"White, Gilbert C."'

1. How we treat a hemophilia A patient with a factor VIII inhibitor.

Author

Kempton CL and White GC 2nd

Subjects
Factor VIII antagonists & inhibitors, Hemophilia A epidemiology, Humans, Isoantibodies immunology, Risk Factors, Factor VIII administration & dosage, Factor VIII immunology, Hemophilia A drug therapy, Hemophilia A immunology, Immune Tolerance
Abstract

The most significant complication of treatment in patients with hemophilia A is the development of alloantibodies that inhibit factor VIII activity. In the presence of inhibitory antibodies, replacement of the missing clotting factor by infusion of factor VIII becomes less effective. Once replacement therapy is ineffective, acute management of bleeding requires agents that bypass factor VIII activity. Long-term management consists of eradicating the inhibitor through immune tolerance. Despite success in the treatment of acute bleeding and inhibitor eradication, there remains an inability to predict or prevent inhibitor formation. Ideally, prediction and ultimately prevention will come with an improved understanding of how patient-specific and treatment-related factors work together to influence anti-factor VIII antibody production.

Published
2009
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2. The Malmö International Brother Study (MIBS). Genetic defects and inhibitor development in siblings with severe hemophilia A.

Author

Astermark J, Oldenburg J, Escobar M, White GC 2nd, and Berntorp E

Subjects
Adult, Child, Child, Preschool, Codon, Nonsense, Family Health, Gene Deletion, Genetic Predisposition to Disease, Humans, Male, Risk, Sweden, Factor VIII genetics, Hemophilia A genetics, Mutation
Abstract

Background and Objectives: The strongest risk factor identified for inhibitor development in people with severe hemophilia A is the type of factor VIII gene mutation. The objective of this study was to evaluate the mutation type dependent concordance rate of inhibitor formation in siblings., Design and Methods: The gene defect, treatment and inhibitor history were evaluated in 113 families in which two or more siblings had severe hemophilia A., Results: Seventy-nine of the families (69.9%) were concordant in that either all or none of the siblings had a history of inhibitors. The concordance in 59 families with inhibitors was 42.4%. The corresponding figures for the 74 families with intron 22 inversion were 63.5% and 40.0%, respectively, and the overall concordance within 14 families with nonsense mutations was 78.6%. The siblings in two families with large gene deletions had no inhibitor history. A small proportion of the families with missense mutations, small deletions/insertions and splice site mutations developed inhibitors, but in four of the families two or more siblings developed high-responding inhibitors. In 18 of the 25 concordant families (72.0%) with inhibitors, the inhibitor was also of the same type (high-responding)., Interpretation and Conclusions: This is the first study of the association between inhibitor formation and the causative factor VIII gene mutation in siblings. The data show that the type of mutation provides, to some extent, the basis for this relationship, but the mutation itself is not enough to predict the risk for therapy-induced inhibitor formation.

Published
2005

3. Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion.

Author

Powell JS, Ragni MV, White GC 2nd, Lusher JM, Hillman-Wiseman C, Moon TE, Cole V, Ramanathan-Girish S, Roehl H, Sajjadi N, Jolly DJ, and Hurst D

Subjects
Adolescent, Adult, DNA, Viral analysis, Factor VIII metabolism, Genetic Vectors adverse effects, Genetic Vectors pharmacokinetics, Humans, Infusions, Intravenous, Leukocytes, Mononuclear physiology, Male, Middle Aged, Severity of Illness Index, Factor VIII genetics, Genetic Therapy, Genetic Vectors administration & dosage, Hemophilia A therapy, Retroviridae genetics
Abstract

In a phase 1 dose escalation study, 13 subjects with hemophilia A received by peripheral intravenous infusion a retroviral vector carrying a B-domain-deleted human factor VIII (hFVIII) gene. Infusions were well tolerated. Tests for replication competent retrovirus have been negative. Polymerase chain reaction (PCR) analyses demonstrate the persistence of vector gene sequences in peripheral blood mononuclear cells in 3 of 3 subjects tested. Factor VIII was measured in serial samples using both a one-stage clotting assay and a chromogenic assay. While no subject had sustained FVIII increases, 9 subjects had FVIII higher than 1% on at least 2 occasions 5 or more days after infusion of exogenous FVIII, with isolated levels that ranged from 2.3% to 19%. Pharmacokinetic parameters of exogenous FVIII infused into subjects 13 weeks after vector infusion showed an increased half-life (T1/2; P <.02) and area under the curve (AUC, P <.04) compared with prestudy values. Bleeding frequency decreased in 5 subjects compared with historical rates. These results demonstrate that this retroviral vector (hFVIII(V)) is safe and, in some subjects, persists more than a year in peripheral blood mononuclear cells, with measurable factor VIII levels and with increased available FVIII activity (increased T1/2 and AUC) after infusion of exogenous FVIII concentrate.

Published
2003
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4. Clinical Trials of Recombinant Factor VIII

Author

White, Gilbert C., II, McMillan, Campbell W., Gomperts, Edward D., Addiego, Joseph E., Jr., Brackmann, Hans H., Brettler, Doreen B., Gill, Joan C., Goldsmith, Jonathon C., Hoots, W. Keith, Kessler, Craig M., Kisker, C. Thomas, Laurian, Y., Lewis, B., Lusher, Jeanne M., Mannucci, Piero M., Morfini, Messimo, Scharrer, Inge, Schulman, Sam, Lee, Martin L., Courter, Suzanne G., Kingdon, Henry S., Roberts, Harold R., Hoyer, Leon W., editor, and Drohan, William N., editor

Published
1991
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5. Hemophilia: An Amazing 35-Year Journey from the Depths of HIV to the Threshold of Cure*

Author

White, Gilbert C.

Subjects
Factor VIII, Transfusion Reaction, HIV Infections, Articles, Genetic Therapy, Hepacivirus, History, 20th Century, Hemophilia A, Protein Engineering, History, 21st Century, Recombinant Proteins, hemic and lymphatic diseases, HIV-1, Humans, Blood Transfusion, Cloning, Molecular
Abstract

Methods developed in the early 1970s to highly purify factor VIII (FVIII) from the plasma of large numbers of blood donors led, for the first time, to concentrates of FVIII that enabled hemophiliac to self-treat, providing independence and opening the way to safe surgery and other treatments. But, with the introduction of blood-borne viruses such as HIV-1 and hepatitis C viruses into the blood supply, these concentrates also transmitted HIV and hepatitis to a high percentage of hemophiliacs. Nevertheless, from the depths of the AIDS epidemic in hemophilia came extraordinary scientific advances that led to recombinant FVIII, the identification of HIV as the agent causing AIDS, the eventual development of effective treatments for AIDS, gene transfer approaches using lentiviruses, and treatments for hepatitis C. All of these have improved the lives of current and future hemophiliacs and have brought us to the threshold of a cure.

Published
2010

6. Mechanisms of B-cell Tolerance

Author

Jacquemin, Marc G., Vanzieleghem, Beatrijs, Saint-Remy, Jean-Marie R., Monroe, Dougald M., editor, Hedner, Ulla, editor, Hoffman, Maureane R., editor, Negrier, Claude, editor, Savidge, Geoffrey F., editor, and White, Gilbert C., II, editor

Published
2001
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10. Factor Viii Inhibitors

Author

Lollar, Pete, Healey, John F., Barrow, Rachel T., Parker, Ernest T., Monroe, Dougald M., editor, Hedner, Ulla, editor, Hoffman, Maureane R., editor, Negrier, Claude, editor, Savidge, Geoffrey F., editor, and White, Gilbert C., II, editor

Published
2001
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15. Apheresis

Author

Nilsson, Inga Marie, Freiburghaus, Christian, Aledort, Louis M., editor, Hoyer, Leon W., editor, Lusher, Jeanne M., editor, Reisner, Howard M., editor, and White, Gilbert C., II, editor

Published
1995
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