Hemoclot thrombin time

All DOAC concentrations were measured using commercial assays, dedicated calibrators, and controls according to the manufacturer’s recommendations: diluted Hemoclot thrombin time with the corresponding calibrator (Hyphen Biomed, Neuville‐sur‐Oise, France); factor Xa inhibitors: STA‐liquid anti‐Xa (Diagnostica Stago, Parsippany, NJ, USA) with drug‐specific calibrators of apixaban, edoxaban, and rivaroxaban (Diagnostica Stago). All measurements apart from TG were performed using the BCS analyzer (Siemens Healthineers, Erlangen, Germany).

Blood samples were collected in citrated vacuum containers via venipuncture. No indwelling catheters were used. Blood was centrifuged at 4000 rpm (1800 g) for 2‐10 minutes to prepare platelet‐poor plasma, aliquoted and stored at −80°C until the analysis was performed. DOAC levels were measured with the STA‐liquid Anti‐Xa (Diagnostica Stago) and the corresponding STA‐Apixaban, STA‐Rivaroxaban and STA‐Edoxaban Calibrator reagents. Dabigatran plasma levels were measured using diluted Hemoclot thrombin time with the corresponding calibrator (Hyphen Biomed). All measurements were performed using the BCS analyzer (Siemens Healthineers).
TG was assessed with the ST Genesia analyzer using STG‐DrugScreen reagent (Diagnostica Stago) according to manufacturer's instruction The principle of the determination of TG with the fully automated and standardized ST Genesia system is similar to the semi‐automated CAT¹² with differences in temperature control and calibration.¹³ Dedicated reagents, calibrators, quality controls, and reference plasmas are used in the ST Genesia. STG‐DrugScreen contains a mixture of phospholipids, recombinant tissue factor (TF) at a relatively high picomolar concentration and uses human thrombin in buffer for calibration. Detailed information about TG measurement with ST Genesia have been previously described.¹¹, ¹³