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Development of a novel automated screening method for detection of FVIII Inhibitors
Author(s) -
Evans M. S.,
Donaldson K. J.,
Eyster M. E.
Publication year - 2017
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.12601
Subject(s) - cutoff , partial thromboplastin time , receiver operating characteristic , area under the curve , predictive value , medicine , coagulation , parallelism (grammar) , detection limit , thrombin generation , clotting factor , computer science , chromatography , chemistry , platelet , thrombin , parallel computing , physics , quantum mechanics
Summary Introduction 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%. Conclusion 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.