title: Development of a novel automated screening method for detection of FVIII Inhibitors.
abstract: BACKGROUND
  Factor VIII activity is routinely determined by measuring the activated partial thromboplastin time (aPTT) of a patient plasma sample and determining percent activity from a standard curve. To maximize the detection of a clotting factor inhibitor, a subjective assessment of parallelism of a patient curve compared with a standard curve is performed. We developed and validated an automated objective method to assess parallelism as a rapid screening tool for detection of an inhibitor to factor VIII during routine FVIII assays.
  
  
  METHODS
  We performed FVIII assays on a subset of FVIII-deficient patients with hemophilia A with and without inhibitors. Utilizing a ratio of the slopes from parallelism curves obtained by an independent Microsoft excel program in patients compared with a normal standard curve, we determined a cutoff ratio predictive for presence of an inhibitor.
  
  
  RESULTS
  A cutoff ratio of patient to control slopes of <0.45 for the detection of an inhibitor to FVIII was 100% sensitive and 91.6% specific, with a positive predictive value of 92.3% and a negative predictive value of 100%.
  
  
  CONCLUSIONS
  Utilizing a ratio of the slopes from parallelism curves in patients with and without an inhibitor, we developed and validated a rapid, automated, and objective method to assess parallelism as an added screening tool for detection of an inhibitor to factor VIII during routine FVIII assays on a STAGO-based coagulation platform. This simple automated method has the potential to detect inhibitors to other clotting factors.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Penn State Health-Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Evans
authors.affiliation: Department of Biochemistry and Molecular Biology, Penn State Health-Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Donaldson
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Penn State Health-Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Eyster
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D001331:Automation; D001780:Blood Coagulation Tests; D005169:Factor VIII / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D006467:Hemophilia A / Q000175:diagnosis; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; C078147:F8 protein, human; D005169:Factor VIII
keywords: 
  FVIII
  ; automated laboratory screening; coagulation inhibitors; hemophilia; inhibitors