28 Analytical Validation of a Novel Point-of-Care Coagulometer for DOAC and Heparin Testing

Abstract

While use of the direct oral anticoagulants (DOACs) and low molecular weight heparin do not currently require routine coagulation monitoring, this can be highly desirable in at-risk patients, including those suffering major trauma or requiring emergency surgery. However, a point-of-care (PoC) device for the rapid measurement of clotting times in these patients is currently not available. The current study characterizes the performance of Perosphere Technologies’ PoC Coagulometer to DOAC- and enoxaparin-induced anticoagulation, as well as characterizes instrument precision, via a methods comparison to manual whole blood clotting time (mWBCT). For each study, whole blood samples from healthy volunteers were spiked with either 0 (sham), 30, 75, 150, 300 and 400 (apixaban, edoxaban) or 450 (rivaroxaban) ng/mL of a DOAC, or 0 (sham), 1, 2, 3, 4, and 5 μg/mL for enoxaparin, in randomized order. A single concentration was tested per day, over 6 days, and samples were tested on 5 PoC Coagulometers and by 5 operators performing mWBCT, simultaneously, for comparison. To assess the agreement of PoC Coagulometer and Manual WBCT measurements, the percent rise of clotting time using Manual WBCT was dichotomized as: 1 when %Rise <=10%, and 0 when %Rise >10%. Each of the five PoC Coagulometers used in the study was randomly paired with one of the five operators for Manual WBCT. The ROC analysis was performed for each anticoagulant using percent rise of clotting time from PoC Coagulometer against the binary status categorized by manual WBCT’s percent rise. Across all concentrations, the sensitivity of the PoC Coagulometer was significantly higher when compared to mWBCT, with absolute values of mWBCT measuring roughly twice those of the PoC Coagulometer. A strong linear correlation was observed for these methods, with R2 values of nearly 1. For individual subjects, mean baseline clotting time, and % rise of clotting time relative to baseline at the lowest and highest anticoagulant concentrations tested for each subject, for both Perosphere Technologies’ PoC Coagulometer and Manual WBCT measurements are compared in Figure 1. The sensitivity of the coagulometer proved to be roughly double that of manual WBCT across the range of concentrations tested. Similarly, the correlation coefficient of clotting time between the two methods for individual subjects yielded R >0.98, indicating a strong correlation between the two methods for individual subject for each anticoagulant. For each individual anticoagulant, the AUC of the ROC curve for coagulometer-operator pairs yielded values of 1 or close to 1 (pair 1 data are shown in Figure 1). Similarly, the other four coagulometer-operator pairs also yielded 1 or close-to-1 AUCs for each individual anticoagulant. These results indicated that the anticoagulant drug response determined by PoC WBCT agreed greatly with the anticoagulant drug response determined by manual WBCT. These results suggest that this PoC Coagulometer could be an ideal measure to assess the pharmacodynamic effects of the DOACs, delivering results within minutes, requiring only a drop of fresh whole blood.