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Evaluation of anti‐factor VIII antibody levels in patients with haemophilia A receiving immune tolerance induction therapy or bypassing agents
Author(s) -
Boylan Brian,
Niemeyer Glenn P.,
Werner Bonnie,
Miller Connie H.
Publication year - 2021
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.14202
Subject(s) - medicine , haemophilia , antibody , haemophilia a , immunology , gastroenterology , coagulation , immunoassay , factor ix , surgery
Abstract Introduction Bleeding episodes in patients who have haemophilia A (HA), a hereditary bleeding disorder caused by a deficiency in factor VIII (FVIII), are treated or prophylactically prevented with infusions of exogenous FVIII. Neutralizing antibodies, referred to as inhibitors, against infusion products are a major complication experienced by up to 30% of patients who have severe HA. Bypassing agents (BPA), a class of therapeutics given to patients who have inhibitors, bypass the need for FVIII in the coagulation cascade, and long‐term inhibitor eradication is accomplished using immune tolerance induction therapy (ITI). Data examining the antibody levels in patients receiving BPA and ITI are limited. Aim Measure anti‐FVIII antibody levels in specimens from patients receiving ITI or BPA in order to evaluate the anti‐FVIII antibody response in those patients. Methods Specimens were tested using the CDC‐modified Nijmegen‐Bethesda assay (NBA) and the CDC fluorescence immunoassay (FLI) for anti‐FVIII IgG 1 and IgG 4 . Results NBA‐negative specimens from patients undergoing ITI or receiving BPAs have a higher frequency of anti‐FVIII IgG 4 positivity compared with the previously published level for NBA‐negative HA patients. Analysis of anti‐FVIII antibody levels in serial samples from patients undergoing ITI reveals that antibodies can persist even after the patient's NBA result falls into the negative range. Conclusions Measurement of anti‐FVIII antibodies may be a useful means to better contextualize NBA results in specimens from patients receiving BPA or ITI. In addition, assessment of anti‐FVIII antibody levels has the potential to improve inhibitor surveillance and clinical decision‐making related to the progress of ITI.