Back to Search
Start Over
Management of haemophilia A-inhibitor patients: clinical and regulatory perspectives
- Source :
- Clinical Reviews in Allergy and Immunology, Clinical Reviews in Allergy and Immunology, Humana Press, 2009, 37 (2), pp.125-34. ⟨10.1007/s12016-009-8115-4⟩
- Publication Year :
- 2009
- Publisher :
- HAL CCSD, 2009.
-
Abstract
- International audience; Inhibitors to factor VIII (FVIII) are alloantibodies directed against epitopes able to neutralise FVIII procoagulant activity. They may render FVIII replacement therapy ineffective. They represent the most severe complication of haemophilia A. At least three mechanisms of FVIII neutralisation activity by anti-FVIII antibodies have been described: (1) steric hindrance; (2) recognition of neo-epitopes and (3) catalytic activity. The Nijmegen modification of the Bethesda is the recommended method for inhibitor surveillance. The occurrence of inhibitors is a relatively frequent and early event in previously untreated patients. Conversely, it is rare in previously treated patients. Therapeutic strategies for managing inhibitors include: inhibitor eradication, haemostatic management of bleeding episodes and/or surgery and supportive care. For high responding inhibitors, immune tolerance induction (ITI) is the strategy for achieving antigen-specific tolerance to FVIII. ITI success rate ranges commonly between 60% and 80%. For treatment of patients with high-titre, high-responding inhibitors, 'by-pass' therapy is generally recommended. Activated prothrombin complex concentrates represent the historically primary 'by-pass' treatment. Recombinant factor VIIa has also been widely used as a by-passing agent. Considering the small patient population, it has to be considered that full immunogenicity data cannot be collected premarketing authorisation. Thus, stringent follow-up of patients in the post-authorisation phase is required.
- Subjects :
- [SDV.BIO]Life Sciences [q-bio]/Biotechnology
MESH: Blood Coagulation Factor Inhibitors
030204 cardiovascular system & hematology
Epitope
Immune tolerance
MESH: Antibodies, Neutralizing
0302 clinical medicine
Isoantibodies
hemic and lymphatic diseases
MESH: Child
Haemophilia A
Immunology and Allergy
Medicine
[INFO.INFO-BT]Computer Science [cs]/Biotechnology
Child
Severe complication
MESH: Treatment Outcome
Clinical Trials as Topic
biology
Blood Coagulation Factor Inhibitors
Immunogenicity
General Medicine
MESH: Factor VIII
3. Good health
Treatment Outcome
Child, Preschool
Antibody
congenital, hereditary, and neonatal diseases and abnormalities
MESH: Immune Tolerance
MESH: Clinical Trials as Topic
Regulatory issues
Haemophilia
Hemophilia A
03 medical and health sciences
Immune Tolerance
Humans
Factor VIII
MESH: Humans
business.industry
Clinical management
MESH: Child, Preschool
FVIII inhibitors
medicine.disease
MESH: Hemophilia A
Antibodies, Neutralizing
MESH: Isoantibodies
Recombinant factor VIIa
Immunology
biology.protein
business
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 10800549
- Database :
- OpenAIRE
- Journal :
- Clinical Reviews in Allergy and Immunology, Clinical Reviews in Allergy and Immunology, Humana Press, 2009, 37 (2), pp.125-34. ⟨10.1007/s12016-009-8115-4⟩
- Accession number :
- edsair.doi.dedup.....40f696011555d1eba62ee1a5b0cb027d