Oral anticoagulation therapy (OAT) is one of the most common medication regimens, with warfarin being by far the most frequently used drug. Its narrow therapeutic range however means that there is a risk on the one hand of bleeding caused by excess drug or, on the other hand, of thrombosis when there is suboptimal anticoagulation. Laboratory monitoring of OAT using prothrombin time (PT) tests is vital. One way to improve the management of OAT, especially for those patients on chronic long-term warfarin therapy, is through the use of handheld point-of-care (POC) testing devices. This article describes such a system for the monitoring of PT/INR.
by Evette Duncan
Warfarin is a commonly used medication for oral anticoagulant therapy (OAT) in patients predisposed to thromboembolism or thrombosis due to atrial fibrillation (AFIB), mechanical heart valve replacement or congenital thrombophilia. Warfarin is a coumarin-based vitamin K antagonist, which decreases blood coagulation by inhibiting the enzyme vitamin K epoxide reductase. This enzyme recycles oxidised vitamin K to its reduced form after it has participated in the carboxylation of several blood coagulation proteins, mainly prothrombin and factor VI.
Patients taking warfarin require regular monitoring using Prothrombin Time (PT) tests. PT and the derived International Normalised Ratio [INR] are measurements of the extrinsic pathway of coagulation and are used to determine the clotting of blood, thus measuring the clinical effectiveness of OAT.
Warfarin is, unfortunately, a less-than-ideal medication due to its narrow therapeutic window; it has a wide variability of responses from patient to patient due to metabolic rate, pharmacodynamics, lifestyle, compliance and its sensitivity to diet and drugs. These factors can markedly increase or decrease the level of effective anticoagulation for any given dose. As a result, patients treated with Warfarin have always been forced to not only comply with a difficult dosage regimen, but also undergo PT/INR testing, which can vary from as often as once a week to once every couple of months, to ensure that their regimen is adequate. Regular monitoring is required to minimise the risk of a thromboembolic event resulting from inadequate anticoagulation, as well as the risk of bleeding due to overanticoagulation [1]. An INR result of less than 2 increases the risk of thromboembolism whilst an INR of more than 4.5 increases the risk of bleeding.
Typically, patients on OAT are required to have a venous blood sample taken on each appointment at their local clinic, hospital or anticoagulation clinic. This sample is then sent to the laboratory for analysis. The PT/INR results are provided to the clinician and then telephoned to the patient, at which point they are given their daily dose regime. This process is not ideal as there are delays with reporting, it is time-consuming and costly for both the patient and healthcare professional.
Point-of-care testing
One way to improve the management of OAT, especially for those patients on chronic long-term warfarin therapy, is through the use of handheld point-of-care (POC) testing devices, such as the INRatio2 platform from Alere. Such devices allow lab-accurate INR/PT test results to be generated in just 60 seconds during a clinic appointment. A small volume of fresh capillary whole blood obtained from a finger stick (as low as 10µL) placed on a disposable test strip that is inserted into the device provides results that are clearly visible on a digital display.
POC testing of INR/PT can eliminate the drawbacks associated with a centralised laboratory approach. The quicker turnaround means that results are not only available at a single patient visit, but enables patients and clinicians to engage in face-to-face testing and consultation of treatment regimes.
Clinicians and health authorities can also benefit from a reduction in short and long term healthcare expenditure as patients remain in the therapeutic range for longer, improving the clinical effectiveness of OAT, and have less side-effects from therapy. Hospital readmissions and treatment costs are significantly reduced, while a quicker turnaround of results requires fewer resources and simplifies workflow. Research has demonstrated, from the perspective of the healthcare provider, that a care model which utilises POC PT/INR testing devices would provide a cost-effective alternative to more traditional care requiring venous blood sampling and laboratory analysis [2].
Home testing
There are two recognised methods of home testing and monitoring of PT/INR:
1) Patient self-testing (PST). With PST, patients measure their own PT/INR with a home testing device and transmit the results to their clinician, often by telephone or via an online system. The clinician then determines the appropriate OAT dosage and provides instructions to the patient on how to proceed.
2) Patient self-management (PSM). Using a home testing device, patients following PSM are able to measure their own PT/INR and, using an agreed protocol, interpret the results and adjust their OAT dosage themselves.
Local healthcare policy often determines whether it is the patient or their clinician who interprets the results and determines the dose of medication. For example, in Germany patients may adjust the medication dose themselves, while in the UK and the USA, this remains in the hands of a healthcare professional. Home testing however, is not suitable for every patient and selected patients must participate in a structured educational programme [1]. Patients must be able to understand and show competency in the testing procedure, in addition to demonstrating a basic theoretical knowledge of blood coagulation, PT/INR interpretation and the adverse effects of over- or under-dosing. Documentation and results should always be communicated to healthcare professionals [1].
Devices such as the INRatio2 system can empower patients to become more knowledgeable and look after their own condition. By providing the freedom of home testing, patients require fewer visits to specialist clinics saving time, money and improving the patient’s quality of life. Home testing allows for more frequent PT/INR testing, proven to increase time in the therapeutic range [3], therefore reducing the risk of clinical complications.
Quality assured results
The INRatio2 monitoring device now has new heparin-insensitive test strips which have recently been CE marked. Heparin is a naturally occurring anticoagulant and is the most commonly used therapy for the initial management of acute cardiovascular diseases prior to starting warfarin therapy. Due to its short half-life of one hour, heparin must be administered regularly or as a continuous infusion. It is therefore only used until OAT with warfarin becomes effective, or in emergency and trauma situations. The heparin insensitivity of the INRatio2 monitoring system means that the management of OAT is improved, resulting in quicker initiation, stabilisation and bridging of warfarin therapy with overall cost saving.
It is important that POC monitoring devices offer high accuracy, precision and quality control (QC). The INRatio2 system utilises a unique 2-level quantitative on-board QC system and does not require any additional control measures. The monitor uses the test strip’s 3-channel technology to perform the PT test and two QC tests (normal and therapeutic) simultaneously. This determines whether the controls are within range before the patient’s INR result is displayed. The unique technology of the INRatio strip enables the two QC tests to be performed alongside the test sample, following laboratory procedure and ensuring that accurate and reliable results are generated every time.
According to guidelines issued by the World Health Organisation (WHO), working thromboplastins used in the prothrombin time (PT) test for the control of OAT must be calibrated against International Reference Preparations to determine the International Sensitivity Index (ISI) necessary to convert PT results into INR [4]. If correctly calibrated, results of tests from different testing devices are reproducible and comparable. The INRatio2 system adheres to these international standards by utilising a thromboplastin reagent with an ISI of 1.0.
Summary
Point-of-care and home testing can significantly increase the time in the therapeutic range and improve a patient’s quality of life. Ultimately, devices such as the INRatio2 can improve the clinical effectiveness of OAT, preventing hospital readmissions due to adverse complications and saving hospital expenditure and resources.
Healthcare professionals can now test and obtain results in 60 seconds, enabling them to immediately advise the patient in one appointment, thereby simplifying workload, and saving time and resources. This saved time allows patients to have face-to-face consultations with their healthcare professional, which can improve patient compliance and therefore increase the clinical effectiveness of OAT.
Patients can now be empowered to look after their own condition, as home testing allows for more frequent testing in the comfort of their own homes. This is proven to increase the time in the therapeutic range and results in fewer clinical complications. Waiting for results, venous blood sampling and regular clinic appointments are no longer necessary.
The Alere INRatio2 PT/INR monitoring system brings laboratory standards to point-of-care and the home
References
1. Braun S, Spannagl M, Voller H. Patient self-testing and self-management of oral anticoagulation. Anal Bioanal Chem 2009; 393:1463-1471
2. Lafata J et al. The Cost-Effectiveness of Different Management Strategies for Patients on Chronic Warfarin Therapy. J Gen Intern Med 2000; 15(1): 31–37
3. Bernado A, Hahuber C, Horskotte D. Home prothrombin estimation. Thrombosis, embolism and bleeding 1992; 325-30
4. The World Health Organization. Regulation of in vitro diagnostic devices: Thromboplastin reagents. www.who.int/bloodproducts/ivd/thromboplastin_reagents/en/ (2010)
The author
Evette Duncan BSc
Alere International
International Product Manager
info.cardiology@alere.com
www.alere.com
