RT Journal Article
SR Electronic
T1 Assessment of in vitro effects of direct thrombin inhibitors and activated factor X inhibitors through clot waveform analysis
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP jclinpath-2018-205517
DO 10.1136/jclinpath-2018-205517
A1 Masatoshi Wakui
A1 Yuta Fujimori
A1 Hisako Katagiri
A1 Shoko Nakamura
A1 Yoshino Kondo
A1 Yuko Kuroda
A1 Terumichi Nakagawa
A1 Nobuko Shimizu
A1 Mitsuru Murata
YR 2018
UL http://jcp.bmj.com/content/early/2018/12/05/jclinpath-2018-205517.abstract
AB Aims Clot waveform analysis (CWA) has been reported to extend the interpretation of clotting time measurement. The parameters obtained from successive derivatives of the clotting reaction curves reflect the rates of activation of individual coagulation factors, theoretically dissecting the cascade pathway. This study aims to assess the in vitro effects of direct thrombin inhibitors (DTIs) and activated factor X (FXa) inhibitors.Methods CWA was applied to the activated partial thromboplastin time (APTT) assay of plasma samples spiked with each drug. For CWA of APTT measurement curves (APTT-CWA), the positive mode of clotting reaction curves was defined as the direction towards fibrin generation.Results All the maximum positive values in the successive derivatives were decreased dependently on the concentrations of each drug. Moreover, the negative values in the second and third derivatives appeared putatively due to consumption of thrombin and factor FXa, respectively, to form complexes with plasma serine protease inhibitors. The decrease of the maximum negative values observed dependently on the concentrations of each drug appeared to be consistent with the decreased generation of thrombin and factor FXa. The analysis of Hill coefficients of each drug in the dose–response of changes in the APTT-CWA parameters revealed a difference in anticoagulant cooperativity between DTIs versus FXa inhibitors.Conclusions The APTT-CWA demonstrated evidence for the blockade of thrombin-positive feedback by DTIs and FXa inhibitors and that for the differences in anticoagulant cooperativity between them. The results demonstrate the usability of CWA for assessment of anticoagulation and provide insights into direct anticoagulants.