A-365 Assessment of Anticoagulant Effect in Non-Responder Patients Taking DOACs at the Point of Care

Background The Perosphere ClotChek™ system (ClotChek) is a novel universal point-of-care coagulation test, that measures Whole Blood Clotting Time (WBCT) reported in seconds. The CE-marked ClotChek is sensitive to Direct Oral Anticoagulants (DOACs) and Low Molecular Weight Heparin (LMWH), and intended to measure the anticoagulation effect of apixaban, rivaroxaban, edoxaban, and enoxaparin accurately and with high precision. With the introduction of DOACs, routine monitoring of patients was no longer required. Nevertheless, there are several clinical situations where there is a need to know the impact of a DOAC to make appropriate clinical decisions. These conditions include: 1) acute major bleeding, 2) the need for emergent surgery or invasive procedures, 3) trauma with potential for major bleeding, 4) compromised renal or hepatic function, 5) extremes of body weight, 6) or concomitant drug use. In lieu of a commercially released DOAC test to measure drug effect, PT/INR and aPTT assays have been used to estimate the level of anticoagulation, but with inconsistent results. This conclusion is consistent with DOAC manufacturers* cautions and warnings regarding these tests. Laboratory calibrated anti-FXa tests have been used to measure the concentration of the drug, but such concentrations have also shown to not always correlate with the resulting anticoagulant effect. Methods A study (Ethics Board approved) was conducted to establish a correlation between the plasma concentration of anti-FXa, measured using a calibrated anti-FXa test (ng/mL), compared to the DOAC anticoagulation effect, as measured by the ClotChek WBCT test (clotting time, seconds). Forty-three donors (63% male) (mean age, 67 years old) receiving apixaban 5 mg twice daily, were recruited. At 2.5 to 3 hours after their last dose, representing their maximal plasma drug concentration, a venous blood sample was obtained to measure the anti-FXa level and ClotChek WBCT. Results All 43 donors tested had DOAC drug concentrations >=75 ng/mL (Figure 1a) (a threshold for meaningful DOAC concentration) but 16% of donor results were below the upper limit of the normal reference interval of ClotChek’s WBCT range (200 to 290 seconds). Conclusion This study suggests that a significant population of individuals prescribed a DOAC may not have a prolonged clotting time as expected when following a prescribed anticoagulation regime and could be classified as a DOAC poor- or non-responder (Figure 1b). Furthermore, this study illustrates how measuring the drug concentration may lead to a misleading interpretation of the resulting anti-FXa concentration, and subsequently the potential risks of assuming an achieved DOAC concentration has yielded an expected therapeutic prolonged clotting time. This poor- or non-response was verified in individual patients by way of analytical measuring range/linearity testing (CLSI EP06-A) in these individuals where increasing DOAC concentration did not yield the corresponding expected increase in clotting times. Additional studies need to be conducted to investigate the basis of the observed lack of correlation between DOAC concentration measured by anti-FXa versus the drug effect, namely the prolongation of the WBCT, and suggests the need for further evaluation of the clinical utility of traditional laboratory anti-FXa testing for DOAC evaluation.