Concept of a point of care test to detect new oral anticoagulants in urine samples

Abstract

New oral anticoagulants (NOAC) are approved for several indications for prophylaxis and treatment of venous thromboembolism and for prevention of embolism in atrial fibrillation at fixed daily doses without need of laboratory guided dose adjustment. Due to their low molecular weight of about 500 to 600 Dalton and their hydrophilicity free anticoagulant is excreted immediately through glomerular filtration into the urine. Impairment of renal function may increase the plasma concentration of the anticoagulants and lowered creatinine clearance is a declared contraindication. In contrast to the initial aim of development the anticoagulant effect is required to be determined in special clinical situations. Several specific and non-specific assays using plasma samples are currently undergoing standardization. As all NOACs are excreted into the urine, specific assays were developed for this matrix to determine them quantitatively of qualitatively. Urine samples can be easily and repetitively obtained avoiding problems and risks associated with blood sampling. The qualitative assay can be performed as a point of care test (POC) also by the patient by judging the different colours for the absence or presence of the drugs with the naked eye. The test is rapid (results available within 15 min), sensitive, specific and accurate and does not require a purified NOAC as control. The tests may be a tool for clinicians who need to know for treatment decisions if a NOAC is on board or not. As the tests are specific for oral direct thrombin inhibitors and for oral direct factor Xa inhibitors, the indication does not interfere with other qualitative POC test in development using clotting systems. The test may be indicated for patients at acute hospitalization, before surgery or central nervous system puncture anaesthesia, if fibrinolytic therapy is indicated, acute deterioration of renal function, and for control of adherence to therapy.

Determination of dabigatran in plasma, serum, and urine samples: comparison of six methods

“…The clinical interest of measuring dabigatran in urine samples may refer also to the lack of availability of plasma samples and for forensic purposes in case of suspicion of overdose. A point-of-care (POC) test clearly separated positive from negative results for dabigatran in urine of patients of treatment [41]. A POC test from whole blood using a PTT reagent also reported a good correlation to plasma concentrations [42].…”

“…This trapping in serum samples seems not to occur for the direct factor Xa inhibitors rivaroxaban and apixaban [20,44]. Preliminary data showed the feasibility of determination of dabigatran in urine quantitatively [45] and qualitatively [41]. Thus, the biological matrices plasma, serum, and urine themselves do not have relevant effects on the interaction of thrombin with dabigatran.…”

“…The time of blood sampling after the intake of the last dose of the anticoagulant plays an important role and needs to be standardized in general. Renal impairment may decrease the excretion of dabigatran, thus reduced renal function may limit the validity of the determination of dabigatran in urine [41].…”

Measurement of dabigatran, rivaroxaban and apixaban in samples of plasma, serum and urine, under real life conditions. An international study

“…So far, measurements under real life conditions have been described for prothrombin time and activated partial thromboplastin time tests from whole blood [20], chromogenic tests from serum and urine [21] and specific POCT colour tests from urine samples [22]. Here we analysed in a larger international, multicentre study, the anticoagulant effects in plasma as well as in serum and urine samples and with a POCT in urine from patients treated with dabigatran, rivaroxaban and apixaban under real life conditions.…”

Direct Oral Anticoagulants in Emergency Trauma Admissions

“…For both tests, results in the reference range beyond 3 h (dabigatran) or 4 h (factor Xa inhibitors) after intake of a direct or non-vitamin-K-dependent oral anticoagulant broadly rule out therapeutic concentrations with a clinically relevant danger of hemorrhage (16,18). Urine test strips for qualitative assessment without clinical validation have been developed (rivaroxaban) or are in the process of development (apixaban and dabigatran) (19); the usefulness of viscoelastic test procedures and endogenous thrombin potential is unclear (e22, e23).…”