4 The diagnostic tests

The interventions

The CoaguChek XS system

4.1 The CoaguChek XS system (Roche Diagnostics) comprises a meter and specifically designed test strips that can analyse a blood sample (fresh capillary blood or fresh untreated whole venous blood) and calculate the prothrombin time and the international normalised ratio (INR). These measures indicate the rate at which the blood clots. If the INR is too low, there is a higher risk of blood clots that can lead to a heart attack or a stroke. If the INR is too high, there is a higher risk of bleeding, which in severe cases can be gastrointestinal or intracerebral bleeding.

4.2 A code chip, which contains calibration data and the expiry date of the test strips, is inserted into the meter before it is switched on. Once the device is switched on, a test strip is inserted and the blood sample is applied. The test result is displayed approximately 1 minute after applying the sample and the monitor automatically stores the result in its memory. The user is guided through the process by on‑screen graphical instructions.

4.3 The CoaguChek XS test strip contains a lyophilised reagent consisting of thromboplastin and a peptide substrate. When a blood sample is applied, thromboplastin activates coagulation, which leads to the formation of thrombin. The enzyme thrombin cleaves the peptide substrate, generating an electrochemical signal. Depending on the time elapsed before it first appears, this signal is then converted by means of an algorithm into customary coagulation units and the result is displayed on the screen. This can be displayed as prothrombin time in seconds, Quick value, or INR.

4.4 The CoaguChek XS system has a number of in‑built quality control functions including checks of the electric components when switched on, the test strip temperature during testing, and checks on the test strip batch such as the expiry date and quality of each strip. The CoaguChek XS test strips are packaged as single strips in resealable plastic containers in quantities of 24 and 48 test strips. The strips can be stored at room temperature or refrigerated between 2 and 8°C and can be used straight from the fridge. On manufacture, the CoaguChek XS test strips have a shelf‑life (expiration date) of 18 months.

4.5 The CoaguChek XS meter is supplied with 4 × AAA batteries, a CoaguChek Softclix finger pricker and 20 Softclix XL lancets, 6 test strips, a user manual and carry case. The system can carry out a minimum of 60 tests per set of batteries. The meter is 138 mm × 78 mm × 28 mm and weighs 127 g (without batteries).

4.6 An earlier model of the CoaguChek XS system is the CoaguChek S system. The CoaguChek XS system is reported to have the following advantages over the CoaguChek S system: the thromboplastin used in the prothrombin time test strips is a human recombinant thromboplastin, which is more sensitive and has a lower international sensitivity index of 1.0 compared with 1.6; test strips have inbuilt quality control that is automatically run with every test; test strips do not have to be refrigerated; a smaller blood sample can be used; and the meter is smaller and lighter. Another model of the CoaguChek XS system is the CoaguChek XS Plus system. The XS Plus model is intended for use by healthcare professionals only and is not indicated for individual INR self‑monitoring.

The INRatio2 PT/INR monitor

4.7 The INRatio2 PT/INR monitor (Alere) does a modified version of the 1‑stage prothrombin time test using a recombinant human thromboplastin reagent. The clot formed in the reaction is detected by the change in the electrical impedance of the sample during the coagulation process. The system consists of a monitor and disposable test strips.

4.8 The monitor provides a user interface, heats the test strip to the appropriate reaction temperature, measures the impedance of blood samples, and calculates and reports prothrombin time and INR results. Instructions and test results are displayed on an LCD. The monitor can store the results so that past test results can be reviewed.

4.9 The test strip comprises 2 layers of transparent plastic laminated to each other that contain 1 sample well, 3 clot cells, and narrow channels connecting the sample well and the clot cells. The top side of the bottom layer is printed with 3 pairs of silver electrodes (1 pair per cell) that start from inside the clot cells to the end of the strip where they are connected to the monitor main circuitry. Test strips are individually foil wrapped, supplied in quantities of 12 or 48 strips and can be stored at room temperature for up to 12 months or until the expiration date.

4.10 The INRatio2 PT/INR monitor analyses fresh capillary blood and when the blood sample is applied to the sample well, it is drawn through the narrow channels by capillary action to the clot cells, where the impedance of the sample is measured by the monitor through the electrodes. Clot cells have reagents applied and the reagents are different for each channel. One channel contains the thromboplastin reagent for the prothrombin time test. The other 2 channels contain reagents that produce a low and high control time, regardless of the clotting time of the sample.

4.11 Initially, the electrode impedance is infinite but drops to a minimum value when the blood sample fills the clot cells. The time when this initial minimum impedance is achieved is registered by the monitor as the start of the coagulation. As the reaction progresses, the sample impedance increases to a maximum and then gradually drops as the clotting proceeds. The elapsed time, in seconds, from the start until the clotting end point is reached is the prothrombin time. The monitor software calculates the INR of the sample using prothrombin time and calibration coefficients.

4.12 The INRatio2 PT/INR monitor does a self‑test when it is turned on and each test strip has a code that is accepted by the monitor if the strip code is in the correct format. The monitor uses 4 × AA batteries or a mains adapter as a power source, and can connect to a printer or computer through the RS232 serial communication port.

The comparator: INR testing

4.13 The comparator used in this assessment is INR testing in primary or secondary care using laboratory analysers or point‑of‑care tests.

  • National Institute for Health and Care Excellence (NICE)