Clinical Validation of a Point-of-Care Whole Blood Coagulometer in Patients on Factor Xa Inhibitors

Abstract

Abstract Background Currently, no sensitive, widely available, rapid turnaround assays to measure the effect on coagulation of direct oral anticoagulants exist. Methods The point-of-care ClotChek (Perosphere Technologies Inc.) coagulometer was developed to address this unmet need with high sensitivity and precision. This proof-of-concept study aimed to determine normal clotting time in healthy, non-anticoagulated subjects; summarize clotting times at trough and peak drug concentrations in patients taking apixaban and rivaroxaban; and identify cut-points that maximize both sensitivity and specificity for predicting whether an individual is meaningfully anticoagulated. Results In 141 normal subjects, the mean clotting time was 244.2 ± 25.8 seconds (median 244.0 seconds; range 183–296 seconds). In 39 patients on apixaban, mean clotting times were 293.9 ± 32.5 seconds at trough and 323.1 ± 27.9 seconds at peak. In 42 patients on rivaroxaban, mean clotting times were 287.8 ± 44.9 seconds at trough and 380.4 ± 41.2 seconds at peak. Strong positive correlations are seen between the anticoagulant drug response determined by the assay and anticoagulant drug levels for apixaban (Spearman's rho = 0.74, p  < 0.0001) and for rivaroxaban (Spearman's rho = 0.82, p  < 0.0001). ClotChek clotting times showed good sensitivity and specificity to identify meaningful anticoagulation (>75 ng/mL) among patients taking apixaban (AUC = 0.91, 83% sensitivity, 86% specificity) or rivaroxaban (AUC = 0.96, 91% sensitivity, 90% specificity). Similar results were seen using the lower threshold of >30 ng/mL. Conclusion These results require clinical validation in further studies but suggest that the ClotChek assay could aid physicians at the point of care in making therapeutic decisions in patients with adverse events associated with oral factor Xa inhibitors.