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A Novel Assessment of Factor VIII Activity by Template Matching Utilizing Weighted Average Parameters from Comprehensive Clot Waveform AnalysisFunding This work was partly supported by a Grant-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to K.N. (18K07885).
Background Activated partial thromboplastin time (aPTT)-based clot waveform analysis is used to evaluate the comprehensive dynamics of fibrin clot formation. In addition, the technique can be usefully utilized for the rapid assessment of factor (F)VIII procoagulant activity in various clinical settings in patients with hemophilia A (HA). We defined a novel algorithm based on the weighted average parameters from aPTT-based waveforms to devise a template-matching procedure for assessing FVIII activity (FVIII:C).
Methods The first derivatives of original clot waveforms triggered by the aPTT reagent (Coagpia APTT-N) were used to determine weighted averages of areas surrounded by the waveform at different percentages of maximum height in various clotting factor-deficient plasmas. Prepared templates based on 50 weighted average-related parameters were compared with 78 aPTT-prolonged plasmas.
Results Original nonsmoothed waveforms of the various clotting factor-deficient plasmas with prolonged aPTTs demonstrated a variety of shapes. The weighted averages were calculated after adjustments for different baselines, and the patterns seemed to be governed by the specific clotting factor deficiency. The weighted average-related parameters including baseline wedge (r 2 = 0.998) and aspect ratio (r 2 = 0.998) were highly correlated with FVIII:C levels. Template-matching analyses based on weighted average-related waveform parameters obtained from 158 samples demonstrated that the sensitivity was 97.2% and specificity was 83.3% in aPTT-prolonged plasmas (n = 78).
Conclusion This novel algorithm based on weighted averages of aPTT-based waveforms together with template-matching may support clinical usefulness for judging of HA and may aid clinical management in the patients in the absence of specific clotting factor assays.
N.S. performed experiments, analyzed the data, interpreted the data, prepared figures, and wrote the manuscript. K.O. analyzed the data and interpreted the data. Y.O., T.K., and S.O. performed experiments, analyzed the data, interpreted the data, and prepared figures. M.S. supervised this study. K.N. designed all experiments, interpreted the data, prepared figures, wrote and edited the manuscript.
An account of this work was presented at the XXVII Congress of the International Society on Thrombosis and Haemostasis, 2019, Melbourne, Australia.
Received: 11 April 2020
Accepted: 23 July 2020
22 August 2020 (online)
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