Interaction of direct oral anticoagulants and other anticoagulants on DOAC Dipstick test

Objective Determination of direct oral anticoagulants (DOACs) in presence of other anticoagulants (ACs) by conventional coagulation assays remains a major challenge in emergency care. In vitro neutralization of ACs improve the validity of coagulation assays but limitations still remain. DOAC Dipstick determines sensitively and specifically direct oral thrombin inhibitor dabigatran (DTI) and direct oral factor Xa (DXI) in urine. We investigated the interaction of DTI and DXI with unfractionated heparin (UFH), low-molecular molecular weight heparins (LMWH), fondaparinux, r-hirudin and argatroban.

Material and Methods Firstly, patient urine samples on treatment with 110 mg or 150 mg bid dabigatran (n=15) and 10 mg rivaroxaban od (n=15) and LMWH subcutaneously (n=30) and controls without AC therapy (n=5) were spiked with each of 0.0, 0.1, and 1.0 IU/mL UFH, LMWH nadroparin, fondaparinux (µg/mL), r-hirudin (µg/mL) and argatroban (mg/mL). Secondly, no or 1 IU/mL antithrombin was added to urine samples of patients treated with UFH, LMWH and fondaparinux. Thirdly, artificial urine samples were spiked with DTI dabigatran and DXIs apixaban, edoxaban, rivaroxaban and at concentrations of 0 ng/mL and 1500 ng/mL in combination with no or with 1 IU/mL UFH or LMWH enoxaparin and 1 µg/mL fondaparinux (n=8 each). Samples were adjudicated by trained observers as negative or positive in absence and presence of a DOAC and an AC by visual evaluation of colours of DTI and DXI pads of DOAC Dipstick.

Results DTI pads were all negative in the absence of dabigatran and absence or presence of UFH, LMWH nadroparin and enoxaparin and fondaparinux. The positivity of all DTI pads in presence of dabigatran did not change in the presence of UFH, LMWH and fondaparinux. The same results were observed on all DXI pads for any DXI, UFH, LMWH and fondaparinux alone and their combinations. DTI and DXI pads were positive in the presence of UFH, LMWH nadroparin and fondaparinux following addition of antithrombin. Results of DTI pads were positive in the presence of high concentrations of r-hirudin and argatroban.

Conclusion The data show a lack of interaction of DOACs with different types of ACs of the heparin classes. DOAC Dipstick determines on a pad creatinine in urine to prevent incorrect determination of by these types of ACs. Detection of ACs in urine such as other direct thrombin inhibitors by DOAC Dipstick warrants further investigation.

Publication History

Article published online:
18 June 2021