Concentration-dependent and platform-specific interference of argatroban and bivalirudin in routine coagulation assays

Argatroban and bivalirudin may interfere with routine coagulation and antithrombin assays through direct thrombin inhibition. However, the magnitude of interference differs across analytical platforms owing to distinct assay principles and reagent formulations. This study aimed to characterize the specific impacts of argatroban and bivalirudin on results of routine coagulation and antithrombin tests on three widely utilized coagulation analytical platforms. Pooled normal human plasma was spiked with clinically relevant concentrations of argatroban (0–2.0 µg/mL) or bivalirudin (0–20 mg/L). Antithrombin (AT) activity, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and Clauss fibrinogen (FIB) were measured simultaneously on all three analytical platforms. Corresponding antigen concentrations of AT and ClaussFIB were quantified via immunoturbidimetric assays to discriminate analytical interference from genuine biological alterations. On Stago and Sysmex platforms, AT activity increased concentration‑dependently with both DTIs, whereas no significant change was observed on Werfen. Fibrinogen levels decreased markedly with argatroban only on Werfen, and with bivalirudin across all three platforms. PT, APTT, and TT were prolonged dose‑dependently on all platforms, though TT frequently exceeded the detection limit at low DTI concentrations. Inter‑platform agreement assessed by intraclass correlation coefficients was poor to moderate for most parameters. Antigen levels remained unchanged, confirming that the observed discrepancies were due to analytical interference. Argatroban and bivalirudin produce significant platform-dependent interference in coagulation testing, particularly in thrombin-based fibrinogen and AT activity assays. Such interference may lead to falsely decreased fibrinogen activity and falsely elevated AT activity. Platform-specific validation and confirmatory testing are essential for accurate interpretation of coagulation results during direct thrombin inhibitor therapy.