Beyond Prothrombin Time and Activated Partial Thromboplastin Time: Clot Formation Rate and Clot Structure Index As Novel Parameters for Coagulation Test Running Head: Novel Parameters of Coagulation Test

BACKGROUND: Coagulation analyzers based on turbidimetry provide clot waveform data. Clotting times are defined only a point on this curve and have limitations to represent the whole characteristics of curve. We investigated to represent the whole curve shape by additional parameters and explored its clinical utility.

METHODS: We applied the Gompertz growth model to the waveform and the two-dimensional curve shape can be expressed with novel parameters. The model was evaluated in terms of fit, applicability, and reproducibility. To understand how the properties of parameters affected by various conditions, we controlled fibrinogen concentration, clot structure, and factor activity. For clinical application of these parameters, a reference interval was established, and the distribution was studied in different populations (normal, lupus anticoagulant-positive, and hemophilia). Finally, they were examined for use as indicators of disease severity in hemophilia and direct oral anticoagulant monitoring.

RESULTS: The model was near-perfectly fitted to the waveform, mostly applicable, and reproducible. Two parameters of the model, κ and α, determined the shape of waveform; κ was linked to the fibrinogen content and clot structure, and α reflected clotting activity and influenced on κ inversely. The clot formation rate (CFR) and clot structure index (CSI), defined using κ and α, provided additive clinical information for hemostatic function evaluation, disease severity estimation, and anticoagulant monitoring beyond the clotting times.

CONCLUSIONS: The clotting curve model enabled to utilize the overall shape of clot waveform. CFR and CSI which derived from the model can be used as additional informative parameters of coagulation test.