Automated screening procedure for the phenotypes of congenital fibrinogen disorders using novel parameters, |min1|c and Ac/|min1|c, obtained from clot waveform analysis using the Clauss method

Abstract

IntroductionFibrinogen activity (Ac) is widely measured, but fibrinogen antigen (Ag) is measured only in specialized laboratories, so it is difficult to discriminate congenital fibrinogen disorders (CFDs) from acquired hypofibrinogenemia (aHypo). In this study, to screen for CFD phenotypes we adopted novel parameters, |min1|c and Ac/ |min1|c, and compared these with validated Ac, Ag, and Ac/Ag, and previously proposed Ac/dH and Ac/|min1|. Materials and MethodsWe calibrated |min1| using a CN-6000 instrument and investigated the correlation between Ag and |min1|c for aHypo (n = 131) and CFD [18 dysfibrinogenemia (Dys), two hypodysfibrinogenemia (Hypodys) and four hypofibrinpogenemia (Hypo)]. Furthermore, we proposed a schema for screening CFD phenotypes using |min1|c and Ac/|min1|c. ResultsThe |min1|c correlated well with Ag in aHypo, and Ac/|min1|c was a better parameter for screening Dys and Hypodys than Ac/dH and Ac/|min1|. With the combination of |min1|c and Ac/|min1|c parameters, 15 Dys, 2 Hypodys and four Hypo were categorized in agreement with the phenotype determined using Ag and Ac/Ag; conversely three Dys were classified as one Hypodys (AαR16C) and two Hypo (BβG15C). ConclusionWe demonstrated that |min1|c and Ac/|min1|c are valuable parameters for screening CFD patients and phenotypes in laboratories that do not measure Ag or perform genetic analysis.