Distinguishing lupus anticoagulants from factor VIII inhibitors in haemophilic and non-haemophilic patients

Details

• Alternative Title:
  Haemophilia
• Personal Author:
  Rampersad, A. G. ; Boylan, B. ; Miller, C. H. ; Shapiro, A.
• Description:
  Introduction:
  
  Accurate diagnosis of an inhibitor, a neutralizing antibody to infused factor VIII (FVIII), is essential for appropriate management of haemophilia A (HA). Low-titre inhibitors may be difficult to diagnose due to high rates of false-positive inhibitor results in that range. Transient low-titre inhibitors and false-positive inhibitors may be due to the presence of a lupus anticoagulant (LA) or other non-specific antibodies. Fluorescence immunoassay (FLI) to detect antibodies to FVIII is a sensitive method to identify inhibitors in HA. Evaluations of antibody profiles by various groups have demonstrated that haemophilic inhibitors detected by Nijmegen-Bethesda (NBA) and chromogenic Bethesda (CBA) assays correlate with positivity for anti-FVIII immunoglobulin (Ig) G1 and G4.
  
  Aim:
  
  This study sought to determine whether FLI could distinguish false-positive FVIII inhibitor results related to LAs from clinically relevant FVIII inhibitors in HA patients.
  
  Methods:
  
  Samples from haemophilic and non-haemophilic subjects were tested for LA, specific FVIII inhibitors by NBA and CBA, and anti-FVIII immunoglobulin profiles by FLI.
  
  Results:
  
  No samples from LA-positive non-haemophilic subjects were positive by FLI for anti-FVIII IgG4. Conversely, 91% of NBA-positive samples from haemophilia subjects were positive for anti-FVIII IgG4. Two of 11 haemophilia subjects had samples negative for anti-FVIII IgG4 and CBA, which likely represented LA rather than FVIII inhibitor presence.
  
  Conclusions:
  
  Assessment of anti-FVIII profiles along with the CBA may be useful to distinguish a clinically relevant low-titre FVIII inhibitor from a transient LA in HA patients.
  
  
• Subjects:
  Adolescent Adult Aged Article Child, Preschool Factor VIII Factor VIII Inhibitor Female Fluorescence Immunoassay Hemophilia A Humans Infant Lupus Anticoagulant Lupus Coagulation Inhibitor Male

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• Source:
  Haemophilia. 24(5):807-814
• Pubmed ID:
  30004159
• Pubmed Central ID:
  PMC6345165
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHS/United States
• Volume:
  24
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:b3e3a9dd2daf6ea20d0bb1e3399392315ff5c38025dd68a0c2c116ec8e05c6d8
• Download URL:
  https://stacks.cdc.gov/view/cdc/70144/cdc_70144_DS1.pdf
• File Type:
  [PDF - 584.20 KB ]