Inhibitor treatment in haemophilias A and B: inhibitor diagnosis.
The clinical diagnosis and quantitative measurement of polyclonal IgG inhibiting antibodies are the subjects of this review. Inhibitors in congenital haemophilia are usually diagnosed either as part of a routine surveillance schedule or following a bleeding episode that responds poorly to standard specific replacement therapy. Routine surveillance schedules for paediatric haemophilia A patients during high-risk incidence periods are variable and the subject of ongoing discussion. There have never been any published recommendations for following haemophilia B patients at high risk for inhibitor development. The Factor VIII/IX Subcommittee of the International Society on Thrombosis and Haemostasis scientifically endorsed the Nijmegen method for inhibitor measurement in 1996. However, there are many unresolved issues surrounding inhibitor diagnosis using these assays. These issues include: (i) questions of accuracy and inter-assay variability inherent to the one-stage clotting assay; (ii) lack of consensus regarding the assay cut-off for negative determination; (iii) lack of assay standardization and (iv) the clinical importance of capturing non-neutralizing antibodies currently not measured in the functional assays. Ongoing efforts to resolve these issues will be discussed.
DiMichele
D M
DM
Department of Pediatrics and Public Health, Weill Medical College of Cornell University, New York, NY 10021, USA. dmdimich@med.cornell.edu
D019774:Blood Coagulation Factor Inhibitors / Q000032:analysis / Q000037:antagonists & inhibitors*; D005164:Factor IX / Q000276:immunology* / Q000627:therapeutic use; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use; D006385:Hemagglutination Inhibition Tests; D006467:Hemophilia A / Q000188:drug therapy / Q000276:immunology*; D002836:Hemophilia B / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*
D019774:Blood Coagulation Factor Inhibitors; D007074:Immunoglobulin G; D005169:Factor VIII; D005164:Factor IX