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Clot waveform analysis using CS ‐2000i™ distinguishes between very low and absent levels of factor VIII activity in patients with severe haemophilia A
Author(s) -
Matsumoto T.,
Nogami K.,
Tabuchi Y.,
Yada K.,
Ogiwara K.,
Kurono H.,
Arai N.,
Shima M.
Publication year - 2017
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.13266
Subject(s) - medicine , haemophilia a , coagulation , thrombin generation , recombinant dna , haemophilia , gastroenterology , surgery , thrombin , platelet , biochemistry , chemistry , gene
Introduction A recently developed method to assess comprehensive coagulation function, clot waveform analysis ( CWA ), accurately detect low levels (<1 IU/dL) of factor VIII activity (FVIII:C) in haemophilia A patients (HA‐pts). Improvements are needed, however, to differentiate patients with very low from absent levels of FVIII :C. Aim We attempted to optimize CWA using the coagulation analyser CS ‐2000i™ to distinguish between very low levels and absent FVIII :C in severe HA ‐pts. Methods and Results Activated partial thrombin time ( aPTT )‐based clot waveforms were determined in FVIII ‐deficient plasmas mixed with various amounts of recombinant FVIII . Clot times ( CT ) were shortened, and maximum coagulation velocity (|min1|) and acceleration (|min2|) were increased in FVIII dose‐dependently at levels ranging from 0.25 to 100 IU/dL. The lowest level of FVIII :C detected was 0.25 IU/dL. Plasma samples from modestly severe ( MS ‐ HA ; 0.5‐<1.0 IU/dL), very severe ( VS ‐ HA ; 0.25‐<0.5 IU/dL), extremely severe ( ES ‐ HA ; <0.25 IU/dL) and inhibitor‐positive HA ‐pts ( HA ‐inh) were examined. The CT was markedly prolonged in all instances but showed significant differences between the different groups insufficiently. The |min1| and |min2| in HA ‐inh were lower compared to the other groups ( P <.05). A new parameter (slope‐|min1|) reflecting average coagulation acceleration was derived. This index (median) was lower in HA ‐inh (0.0042) compared to ES ‐ HA (0.0068) and VS ‐ HA (0.011) with greater significant differences ( P <.01), and an index of <.005 reflected the total absence of FVIII in the presence of inhibitor. Conclusion The slope‐|min1| parameter could provide a useful index for evaluating very low and absent levels of FVIII and/or the development of FVIII inhibitor in HA ‐pts.