Guideline For Using Point of Care INR Monitoring of Warfarin Therapy
What is a Point of Care (POC) INR Device?
For both adults and children, use of a POC INR device provides a simple way to improve oral anticoagulation management both in the office setting and at home 1-3. The POC INR device requires a small blood sample, produces an INR result within one minute, enables timely drug dose adjustment, and allows prompt attention to INR values that fall substantially outside of the therapeutic range. INR measurements can be performed at a patient’s convenience and use of a POC INR device eliminates the need for laboratory visits. This convenience facilitates more frequent INR testing. Furthermore, in randomized trials comparing POC with laboratory-based INR monitoring, POC-based monitoring has been shown to improve the quality of anticoagulation control (time in therapeutic range) and to reduce thromboembolic and hemorrhagic events4.
POC INR devices measure a clotting time from a fingerstick whole blood sample. Although they have unique characteristics, POC INR devices have a similar mode of action. Each device uses coded test strips (cartridges). Each package of test strips comes with a code chip linked to the expiry date of the test strips. The code chip must be inserted into the POC INR device prior to using test strips. The test strip is inserted into the device and warmed to 37°C. A drop of capillary whole blood is placed onto the test strip and is drawn into the machine by capillary action. The blood sample combines with an activator of the coagulation system (thromboplastin) and flows through the device until clot formation is detected. The time elapsed from the whole blood and thromboplastin mixing to detection of clot formation equates to the prothrombin time (PT), which is converted to an INR. Most POC devices report the result as either a PT or as an INR5.
The POC INR devices vary in their ease of use due to differences in blood sample volume required, the technique of application of blood sample to meter, the need for external quality control testing, refrigeration of test strips, and meter portability.
Three different modes of POC INR monitoring and management have been utilized:
- POC INR testing within a health care facility (hospital or clinic) wherein patients receive immediate INR results and instructions on drug dosage.
- POC INR testing in the home with results phoned to an anticoagulation clinic or physician followed by instructions on drug dosing (self-testing).
- POC INR testing in the home with patients undertaking self-dosing using a predetermined dosing nomogram combined with their own experience. (self-testing and self-monitoring).
What is the Accuracy and Precision of POC INR Devices?
Numerous studies have assessed the accuracy and precision of POC INR devices in both adults and children. The accuracy and precision of POC devices are inconsistent and less accurate when an INR is above the therapeutic range (i.e., INR >3.5) or, for some devices, when a patient has antiphospholipid antibodies. In general, when comparisons are made between laboratory-based and POC-based INR measurements within the usual therapeutic range, the difference between values are <15%. Such a difference is acceptable as it is similar to that of INR results done in different laboratories using anticoagulated plasmas that are simultaneously compared using different instrument and/or thromboplastin reagents6.
How does one Define Clinically Important Differences in INR between POC and Laboratory-based Measurements?
Although there may be numeric differences in INR results between POC- and laboratory-based INR measurements (e.g., INR of 2.2 and 2.7), such differences may not be clinically important. One way to assess whether the difference in INR results is clinically important is to determine if they would result in different dosing of oral anticoagulants, typically warfarin. For example, INR measurements of 2.2 and 2.7 using a POC and laboratory-based method, respectively, would not typically lead to a change in warfarin dose. On the other hand, INR measurements of 2.9 and 3.4 (same numeric difference) may result in a dose reduction when the higher INR is reported. Given these considerations, there are several ways to determine whether the INR results are clinically comparable (i.e., not leading to different warfarin dosing) or clinically different (i.e., leading to different warfarin dosing). Thus, INRs from a POC device and laboratory may be considered comparable if they satisfy the following criteria for agreement7, 8.
1) both INRs are within the targeted INR range (e.g., INR of 2.2 and 2.7) for patients receiving warfarin with a targeted INR range of 2.0-3.0
2) both INRs are within 0.5 units, irrespective if one or both are within the targeted INR range (e.g., INR of 2.9 and 3.4) for patients receiving warfarin with a targeted INR range of 2.0-3.0
What are some Considerations Prior to POC INR Device Use?
Before a POC INR device is used to guide patient care, we suggest the following to ensure proper use of the INR device and optimal patient safety:
1) Patients selected for POC INR use must demonstrate good adherence to treatment.
2) At least three comparisons between POC-based and laboratory-based INR measurements should be done to evaluate the accuracy of the POC INR device in a given patient. Above-mentioned criteria for agreement can be used to assess accuracy in INR measurements of the POC device.
3) Patients in whom INR testing with a POC INR device are planned should participate in a standardized educational program to ensure proficiency in testing technique. A standardized validated educational tool is available titled KIDCLOT© POC. This tool describes CoaguChek XS meter (Roche Diagnostics, Basil,Switzerland). Although this tool is designed for children it can be used successfully with adults.
4) Relationship with an anticoagulation clinic and a primary care physician familiar with POC INR testing is essential so the patient may access this professional for expert advise if needed or trouble-shooting.
5) Ongoing quality assurance (laboratory-meter comparisons) should be performed every 6-12 months or when after changing test strips (cartridges) to reassess device accuracy and the integrity of the test strips.
6) Electronic quality control should be performed as indicated by the POC device’s manufacturer
Patient Self-Management
Self-management empowers the patient to participate in and manage their therapy in a manner similar to glucose self-monitoring and diabetes management. Self managed care assumes that patients taught to accurately self test using a POC INR device and are able to successfully manage their warfarin therapy.
In clinical trials involving adults who required long-term oral anticoagulant therapy, self-management of anticoagulant therapy using a POC INR device is associated with cost savings to the health care system as well as to the patient3. Self-management of anticoagulation also confers moderate improvement in the time within the therapeutic range1, and improvements in patients’ quality of life1, 3, 9, 10. Most importantly, perhaps, oral anticoagulant therapy self-management has the potential to reduce adverse clinical outcomes (thromboembolism, bleeding).
References
1. Ansell J, Jacobson A, Levy J, Voller H, Hasenkam JM, International Self-Monitoring Association for Oral A. Guidelines for implementation of patient self-testing and patient self-management of oral anticoagulation. International consensus guidelines prepared by International Self-Monitoring Association for Oral Anticoagulation. International Journal of Cardiology 2005;99(1):37-45.
2. Bauman M, Conroy S, Massicotte M. POC INR Measurement in Children Requiring Warfarin: What has been Evaluated and Future Directions. Pediatric Health 2008;October (in press).
3. Douketis JD. Patient self-monitoring of oral anticoagulant therapy: potential benefits and implications for clinical practice. Am J Cardiovasc Drugs 2001;1(4):245-51.
4. Heneghan C, Alonso-Coello P, Garcia-Alamino JM, Perera R, Meats E, Glasziou P. Self-monitoring of oral anticoagulation: A systematic review and meta-analysis. Lancet 2006;367(9508):404-11.
5. D'Angelo A, Seveso MP, D'Angelo SV, et al. Comparison of two automated coagulometers and the manual tilt-tube method for the determination of prothrombin time. Am J Clin Pathol 1989;92(3):321-8.
6. Ng VL, Levin J, Corash L, Gottfried EL. Failure of the International Normalized Ratio to generate consistent results within a local medical community. Am J Clin Pathol 1993;99(6):689-94.
7. Anderson DR, Harrison L, Hirsh J. Evaluation of a portable prothrombin time monitor for home use by patients who require long-term oral anticoagulant therapy. Arch Intern Med 1993;153(12):1441-7.
8. Shermock KM, Bragg L, Connor JT, Fink J, Mazzoli G, Kottke-Marchant K. Differences in warfarin dosing decisions based on international normalized ratio measurements with two point-of-care testing devices and a reference laboratory measurement. Pharmacotherapy 2002;22(11):1397-404.
9. Christensen TD, Andersen NT, Attermann J, Hjortdal VE, Maegaard M, Hasenkam JM. Mechanical heart valve patients can manage oral anticoagulant therapy themselves.[see comment]. Eur J Cardiothorac Surg 2003;23(3):292-8.
10. Christensen TD, Attermann J, Pilegaard HK, Andersen NT, Maegaard M, Hasenkam JM. Self-management of oral anticoagulant therapy for mechanical heart valve patients.[see comment]. Scandinavian Cardiovascular Journal 2001;35(2):107-13.