Advice

The technology

The technology

The DOAC Dipstick (DOASENSE GmbH) is a single-use, point-of-care dipstick test that is used to detect direct oral anticoagulants (DOACs) in urine. The urine dipstick test detects DOACs (both factor Xa inhibitors and thrombin inhibitors) based on colour-changing chemical reactions that happen on the surface of the DOAC Dipstick test pads. Each dipstick test strip contains 4 test pads to detect:

  • direct oral thrombin inhibitors (dabigatran – pad 4)

  • direct oral factor Xa inhibitors (apixaban, edoxaban and rivaroxaban – pad 3)

  • urine colour (validation pad to help exclude abnormal urine colour that can affect results – pad 2)

  • creatinine (validation pad to help exclude impaired renal function that can affect results – pad 1).

The test is done by immersing the test strips in a urine sample for 2 to 3 seconds, removing excess liquid using a tissue, and placing on a flat surface for 10 minutes. Then results can be determined. Colour identification can be done with the naked eye using the corresponding colour scales on the tube label, or with an automated reader (DOASENSE Reader).

According to the product's instruction for use, the cut-off value of apixaban, edoxaban and rivaroxaban for a negative test result is less than 100 ng/ml, and the cut-off value for a positive test result is over 200 ng/ml. The cut-off value of dabigatran for a negative result is less than 50 ng/ml and for a positive result it is more than 125 ng/ml. In the ranges between the cut-off values the colours of the results for the DOACs may be identified as either negative or positive.

Innovations

The company states that the DOAC Dipstick is the only test approved for point-of-care testing of DOACs. Results are available within 10 minutes, which may lead to more timely medical treatment decisions. This could include administering a reversal agent for thrombin or factor Xa inhibitors, or directing a person to surgery. In addition, the DOAC Dipstick is a less invasive method of DOAC testing compared with currently available laboratory tests for DOAC detection, which may involve collecting blood samples from people.

Current care pathway

DOACs are a group of anticoagulating substances that directly inhibit specific clotting factors such as factor Xa and thrombin. They are used to prevent and treat thromboembolism across various clinical indications. The 4 DOACs currently licensed in the UK are apixaban, dabigatran etexilate, edoxaban and rivaroxaban. Routine coagulation monitoring for people taking DOACs is not needed. However, there are some clinical situations when the measurement of DOAC activity may be useful to help with clinical decision making and subsequent management:

  • In people admitted to emergency departments with an acute bleed, to understand whether anticoagulation is the cause of the bleed.

  • In people needing emergency surgery to understand whether the person has taken DOACs before the procedure.

  • Before elective surgery in people on DOAC therapy, to rule out the presence of residual DOACs.

Laboratory tests are available that may provide useful information about the levels of DOAC in blood in these situations. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is considered gold standard for the measurement of DOACs. However, LC-MS/MS is not widely available, needs a relatively high level of expertise and is time-consuming. Other more accessible laboratory tests are available, including:

  • thrombin time

  • prothrombin time

  • activated partial thromboplastin time

  • plasma-diluted thrombin time or direct thrombin inhibitor assay (Hemoclot)

  • drug-specific anti-Xa assays (available for rivaroxaban, apixaban and edoxaban).

Experts who commented on this briefing said that the availability of these laboratory tests may vary between centres. Specific assays can accurately quantitate drug levels, however they can be expensive, they are not available in all laboratories and require particular expertise.

Due to its high degree of specificity, sensitivity, selectivity and reproducibility, LC-MS/MS is considered the gold standard method for the measurement of DOACs.

The DOACs have differing impacts on the common tests of haemostasis and it is important that clinicians are familiar with the sensitivity of the reagents used in their laboratory to individual DOACs.

Each DOAC is known to produce unique effects on coagulation assays. The sensitivities of these tests can vary widely depending on the DOAC drug and reagents used and cannot be standardised across laboratories. Some tests (such as prothrombin time and activated partial thromboplastin time) may not be reliable to detect therapeutic concentrations of all DOACs. Experts who commented on this briefing said that the availability of these laboratory tests may vary between centres.

In emergency situations, when a person is suspected to have taken a DOAC recently before admission, an appropriate reversal agent may be given. This depends on the DOAC taken (idarucizumab is used for dabigatran, andexanet alfa for apixaban or rivaroxaban, and prothrombin complex concentrate is used when specific reversal agents are not available).

The following publications have been identified as relevant to this care pathway:

Population, setting and intended user

According to the company, there are currently more than 1 million people having DOAC therapy in the UK. Licensed oral anticoagulants that are used in the UK include warfarin, and the DOACs apixaban, dabigatran etexilate, edoxaban and rivaroxaban. The most common adverse effect of anticoagulants is bleeding, ranging from mild events to serious and fatal haemorrhage. The DOAC Dipstick is intended to test for DOACs in people arriving at emergency departments with acute bleeding or haemorrhagic stroke, or in people needing emergency surgery when the presence of DOACs needs to be ruled out. DOAC Dipstick can also be used to rule out the presence of residual DOACs in people before elective surgery. The test would be done in secondary care by healthcare professionals working in emergency, stroke or surgical departments. According to experts who commented on this briefing, the test is simple to do and would be done by healthcare assistants or nursing staff.

Costs

Technology costs

The DOAC Dipstick test costs around £15 per strip (excluding VAT). The technology is available in packs of 12 test strips. The test is not yet launched in the UK. The company states that the technology is expected to be available in the UK by February 2021.

Costs of standard care

The unit cost of a standard laboratory haemostasis test is approximately £34. This includes the cost of the test itself (£30; cost taken from NICE's guideline on routine preoperative tests for elective surgery and inflated to 2019 prices) and the cost of staff time and equipment needed to collect the blood sample (£4; NHS reference costs 2018/19 for phlebotomy).

Resource consequences

The technology could be resource releasing if it results in earlier clinical decisions that lead to improvements in clinical outcomes for patients and reductions in length of hospital stay. The company also states that the DOAC Dipstick may allow increased flexibility in operating room scheduling, which could free up recovery and intensive care unit beds earlier. There is no published evidence to support these claims. Experts who commented on this briefing said the test is a simple point-of-care test and appears to be easy to do and interpret, with minimal training needed.