Sta eca 2

Blood samples were collected in 3 mL tubes containing buffered trisodium citrate 3.2% (S-Monovette; Sarstedt AG, Nürmbrecht, Germany), with a citrate:blood volume ratio of 1:9. After centrifugation (2500 G for 10 min), the DOAC concentration was measured in platelet-poor plasma on STA Compact Max 3 (Diagnostica Stago, Asnieres, France) device using specific chromogenic tests. For dabigatran, STA-ECA II (Diagnostica Stago, Asnieres, France) was used. For the measurement of the direct factor Xa-inhibitors apixaban, edoxaban, and rivaroxaban, the STA-Liquid Anti-Xa assay with dedicated calibrators (Diagnostica Stago, Asnieres, France) were applied. Moreover, the standard coagulation test prothrombin time (PT, reference limit 11–16.1 s; STA-NeoPTimal; Diagnostica STAGO, Asnieres, France) and activated partial thromboplastin time (aPTT, reference limit 24–35 s; Cephascreen; Diagnostica STAGO, Asnieres, France) were measured with the same device.

The prothrombin time-based international normalized ratio (INR) and the activated partial thromboplastin time (aPTT) were determined with the reagents Hepato Prest and STA aPTT-A, respectively (Diagnostica Stago, Asnieres, France). The main outcome parameter was the blood concentration of DOACs, which was determined in plasma obtained from citrated venous blood immediately before (trough level) and two to three hours after drug intake (peak level). DOACs were administered in the presence of the treating physician, and rivaroxaban was taken together with food. Drug concentrations were determined by chromogenic anti-Xa assays calibrated for apixaban, edoxaban, or rivaroxaban (STA Liquid Anti-Xa, Diagnostica Stago, Asnieres, France) or by an Ecarin chromogenic assay for dabigatran (STA-ECA II, Diagnostica Stago). Respective calibrators and controls were obtained from Diagnostica Stago. Expected ranges for trough and peak levels differed depending on the DOAC and the respective dosage and indication, and were adopted according to the “International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants” [20 (link)].
All coagulation assays were performed fully automated on a STA-R Max2 analyzer (Diagnostica Stago).

Concentrations of dabigatran were estimated using one Ecarin chromogenic assay (STA-ECA-II, Diagnostica Stago), and concentrations of apixaban, edoxaban, and rivaroxaban with the corresponding procedure using the chromogenic assay (STA-liquid anti-Xa, Diagnostica Stago). All these procedures were performed on the STA-R MAX analyzer (Diagnostica Stago). The limit of quantification of the corresponding apixaban, dabigatran, edoxaban, and rivaroxaban assays were 15, 27, 20, and 25 ng/mL, respectively.
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