Poor comparability of coagulation screening test with specific measurement in patients receiving direct oral anticoagulants: results from a multicenter/multiplatform study

Abstract

Background Prothrombin time (PT) and activated partial thromboplastin time (APTT) have been proposed to measure the effect of oral anti-activated factor X (FXa) or anti-activated FII drugs, respectively. Aims To evaluate the relationships and responsiveness of PT and APTT versus direct oral anticoagulant (DOAC) concentrations measured with specific coagulation tests performed with different platforms in four Italian anticoagulation clinics. Methods Six hundred and thirty-five patients with atrial fibrillation participated in the study: 240 were receiving dabigatran, 264 were receiving rivaroxaban, and 131 were receiving apixaban. Blood was taken at trough and peak within the first month (15-25 days) of treatment. PT, APTT, diluted thrombin time (dTT) calibrated for dabigatran and anti-FXa calibrated for rivaroxaban or apixaban were determined. Results For dabigatran, the correlation between APTT and dTT ranged from r = 0.80 to r = 0.62. For rivaroxaban, the correlation between the anti-FXa assay and PT ranged from r = 0.91 to r = 0.73. For apixaban, the correlation between the anti-FXa assay and PT was lower than for the two other drugs (r = 0.81 to r = 0.54). Despite the above significant correlations, the responsiveness of PT or APTT was relatively poor. A discrepancy between global testing and DOAC plasma concentrations was shown in a considerable proportion of patients, depending on the platform and drug, with values ranging from 6% to 62%. Conclusions Overall, poor responsiveness of the screening tests to DOAC concentrations was observed. PT and APTT normal values cannot exclude DOAC anticoagulant activity, and PT or APTT prolongation is not always associated with DOAC anticoagulant effect as determined with specific tests.

Early prediction of postoperative liver dysfunction and clinical outcome using antithrombin III-activity

“…Via inhibition of thrombin, factor Xa, but also of factors IXa, XIa, XIIa, tissue plasminogen activator (tPA), trypsin, plasmin, urokinase and kallikrein, ATIII acts as a physiologic anticoagulant[28]. It is well known that PT is prolonged by a series of conditions, including direct acting anticoagulants (among them argatroban, dabigatran, rivaroxaban, apixaban, edoxaban)[29] and intake of vitamin K antagonists[30], vitamin K deficiency[31], coagulation factor deficiency, lupus anticoagulans[32], polycitemia vera[33]. Similarly, it was shown that factor VII deficiency is frequent in patients with infections, neoplasia, trauma, nephrotic syndrome, left heart failure, penicillin intake and clearly in patients under vitamin K dependent anticoagulation[34, 35].…”

Measurement of rivaroxaban concentrations demonstrates lack of clinical utility of a PT, dPT and APTT test in estimating levels

“…However, overall of 26 patients who had rivaroxaban concentrations less than 90 ng/mL, 20 had prolonged PT or aPTT or both. In addition, the extent of prolongation of both PT and aPTT correlated poorly with rivaroxaban concentration limiting their use as a clinical predictor of anticoagulant intensity as previously observed . In the Einstein studies, the mean trough level of rivaroxaban was 32 ng/mL .…”

Management of major bleeding and outcomes in patients treated with direct oral anticoagulants: results from the START-Event registry

“…This observation opens the question about the importance of laboratory testing in emergency clinical conditions to address appropriate treatments. As previously shown [21], global coagulation tests such as PT and aPTT are not useful to quantify DOAC activity, while specific tests (anti-Xa, dTT, ecarin test) are available and easily adaptable on most commercial coagulation platform. Despite the increasing consensus on the need for DOAC measurement in specific clinical conditions, our study shows a low rate of specific drug measurements in emergency situations, highlighting an urgent need for their implementation in each hospital.…”

“…Laboratory tests included: blood cell count, liver enzymes (AST, ALT), renal function (creatinine clearance calculated using the Cockcroft-Gault formula), coagulation screening tests (PT and aPTT), and specific DOAC measurements. DOACs levels, expressed as drug concentration equivalent (ng/ml), were measured with diluted thrombin time (dTT) or ecarin chromogenic assay (ECA) calibrated for dabigatran and specific anti-factor X activated (FXa) assays calibrated for apixaban, edoxaban, and rivaroxaban [12,21,22]. All tests were performed locally, and each investigator made decision on whether to perform laboratory or not.…”