Evaluation of anti-factor VIII antibody levels in patients with haemophilia A receiving immune tolerance induction therapy or bypassing agents

Details

• Alternative Title:
  Haemophilia
• Personal Author:
  Boylan, Brian ; Niemeyer, Glenn P. ; Werner, Bonnie ; Miller, Connie H.
• Description:
  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 IgG1 and IgG4.
  
  Results:
  
  NBA-negative specimens from patients undergoing ITI or receiving BPAs have a higher frequency of anti-FVIII IgG4 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.
  
  
• Subjects:
  Article Factor VIII Factor VIII Deficiency Haemophilia A Immunoassay Immunology Inherited Blood Coagulation Disorders
• Source:
  Haemophilia. 27(1):e40-e50
• Pubmed ID:
  33216433
• Pubmed Central ID:
  PMC8040055
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHS/United States ; CDC Foundation/
• Volume:
  27
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:8150b963b9a53f16abab25cd0ce710cd694aac34c04554467a01fc09cef8ab00
• Download URL:
  https://stacks.cdc.gov/view/cdc/105259/cdc_105259_DS1.pdf
• File Type:
  [PDF - 453.37 KB ]