Article

International Normalized Range Monitoring for Anticoagulated Patients at Home

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Oral anticoagulants are one of the most common causes of drug-induced adverse events.1 Expert dose management, which keeps the patient within a narrow therapeutic international normalized range (INR), is required to avoid adverse events and optimize therapy. Anticoagulation clinic (ACC) management has been shown to improve outcomes compared with the routine management provided by physicians,2 but estimates suggest that fewer than 50% of patients in the US on oral anticoagulants are managed by such clinics. Point-of-care (POC) prothrombin time monitoring technology, developed 20 years ago, introduced a new model of care by allowing for fingerstick INR monitoring and patient self-testing (PST). Under this model, patients may either monitor their own INR at home and receive dose-adjustment guidelines from their physician, or actually adjust their own anticoagulation dose after proper training.2 Numerous published clinical studies conducted during the past 10 years have validated the benefits and value of POC testing for anticoagulation monitoring compared with venous blood draws and laboratory testing. Despite the clinical evidence, many healthcare professionals have been reluctant to incorporate POC testing into their practices. There are several devices available for self-testing that rely on capillary whole blood and are lightweight, portable, easy-to-use, accurate, and precise (see Table 1). INR results from these portable devices have been shown to equal those from phlebotomy plasma INRs determined in a central laboratory.3

Patient Self-testing/Patient Self-management

Many studies4–28 have reported on the accuracy and precision of POC instruments when used by patients to obtain an INR, and on the suitability of POC instruments for monitoring anticoagulant therapy. Limitations to their accuracy and precision include greater differences compared with a standard plasma-based methodology as INRs increase above the therapeutic range,6,26 incorrect calibration of the international sensitivity index (ISI) of the POC instruments,6 the inability to calculate a mean normal prothrombin time (PT),27 and inaccuracies in INR determination in patients with antiphospholipid antibodies. Multiple studies focusing on clinical outcomes and patient satisfaction have determined the suitability of PST.

It is important to note the comparator group used in controlled trials, since this influences differences. When a usual care (UC) model of anticoagulation management is the comparator group, the PST or patient self-management (PSM) arms will often show marked improvement in time in therapeutic range (TTR, a surrogate measure of quality) or in efficacy and safety outcomes. Alternatively, when PST or PSM is compared with a control arm managed by an ACC, the differences are minimal. Table 2 summarizes randomized trials in which 50 or more patients were studied and clinical outcomes were reported as TTR, adverse events, or both.27–37 Studies were stratified by whether they were PST versus PSM trials and the control groups were UC or ACC care. In a large randomized study, Beyth et al.27 compared PST with UC management. The PST group had a 5.6% incidence of major hemorrhage compared with a 12% incidence in the UC group (p=0.049). Venous thrombosis occurred at a rate of 8.6% in the PST group compared with 13% in the UC group, but the difference was not significant. In a number of trials comparing PSM with UC, mean TTR for the PSM arms was 73% versus 59.9% for the UC arms.28,34–36,38–41 None of these trials showed differences in major hemorrhage or thrombosis, although none of them were powered to do so. When one assesses the outcomes of PST compared with management by an AC, the TTR is only minimally improved (73.3 and 67.1%, respectively).32,33,38 The same is found when PSM is compared with AC care (71.4 and 66.6%, respectively).29,30,37

Only one trial found a significant difference in the rate of major bleeding and thromboembolism.30 These studies and others have been the subject of several detailed meta-analyses.42,43 These meta-analyses are somewhat problematic in that some combine results from PSM and PST, while in others the controls are a combination of UC and ACC management. In the most comprehensive meta-analysis to date, Heneghan et al. pooled estimates from 14 randomized trials of PST showing a significant reduction in thromboembolic events (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.30–0.68), all-cause mortality (OR 0.61, 95% CI 0.38–0.98), and major hemorrhage (OR 0.65, 95% CI 0.42–0.99) versus the comparator.42 For PST and PSM combined, there were significant reductions in thromboembolic events (OR 0.27, 95% CI 0.12–0.59) and death (OR 0.37, 95% CI 0.16–0.85), but not major hemorrhage (OR 0.93, 95% CI 0.42–2.05). Both PST and PSM studies are included.

Based on these data, portable PT monitors offer the potential to lower the risk–benefit ratio of anticoagulant therapy, improve patient satisfaction and possibly patient compliance, and, by reducing the labor intensity of physician management, encourage the use of warfarin when indicated. Although larger randomized, prospective trials are needed, current data suggest that future management of anticoagulation should include PST and PSM therapy. This fact was recognized by the most recent American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy, where the following recommendation was made: “PSM is a choice made by patients and healthcare providers that depends on many factors. In patients who are suitably selected and trained, PST or PSM is an effective alternative treatment model. We suggest that such therapeutic management be implemented where suitable (Grade 2B).“2

Patient Education

While generalized training guidelines for PSM of any disease state apply to self-anticoagulation, the high risk–benefit ratio of warfarin and the potentially serious consequences of non-therapeutic levels of anticoagulation warrant special considerations in patient education. The majority of patients taking oral anticoagulants are older with multiple co-morbidities that require special attention. Patient education must begin with candidate identification. Certainly, not all patients are able or willing to perform the test and keep the necessary records to ensure safe and accurate monitoring. The most important consideration in choosing good candidates is incentive. Incentives differ among patients. Less frequent clinic visits, particularly for patients who have difficulty reaching the clinic, may be sufficient for some patients, whereas patients who have an aversion to phlebotomy or poor venous access might appreciate the ease of obtaining results from a fingerstick. Some patients are excited to learn about their conditions and to actively participate in their care. Patients at an increased risk for hemorrhage, or individuals whose PT fluctuates widely, might welcome the opportunity for more frequent and less invasive monitoring. For some patients, a trusted physician’s recommendation will suffice. Other important considerations in the identification of good candidates include the adequacy of motor skills to perform the test, sufficient mentation and memory, sufficient literacy, and adequate eyesight, with or without glasses, to see the device screen.

Patients who have the potential to benefit the most include those who have limited access to testing due to distance or disability and those who require increased testing frequency (i.e. those patients with heart failure, liver cirrhosis, or marked variation in PT values). For children or patients with disabilities that would preclude their ability to competently perform their own testing, the availability of a parent, spouse, or qualified care provider allows these patients to be considered for PST.

There are two aspects of patient education: patients must be educated about anticoagulation so that they understand what, where, and why they are performing the test, and they must also be trained in the use of the monitor.

The challenge for the healthcare provider is to convey the necessary information to the patient and train the patient in the use of the monitor without conveying excessive information. Ideally, training would be provided by a multidisciplinary team including nursing, pharmacy, laboratory, and dietary staff. Topics to be covered include: mechanism of anticoagulant action; importance of maintaining a therapeutic range; interpretation of test results; factors that affect the PT—diet, drugs, and liver function; bleeding risks and monitoring; testing frequency; and indication and duration of therapy. Trainers should simplify the process as much as possible and provide written instructions in short, clear, simply phrased sentences. The tasks allocated to the patient should be clearly listed in simple, straightforward, consistent terms, and should be located in an easily accessible place. The trainer should refer to the list throughout the training session. When instructing patients in the actual use of the instrument, the trainer must remember that the majority of patients are not comfortable with electronics and thus may be intimidated by the apparent complexity of the monitoring device and its accompanying materials. The trainer should remember that older patients often benefit from consistency, and their routine should be disrupted as little as possible. For a patient who is accustomed to laboratory phlebotomy and a subsequent telephone call regarding dosage changes, the instrument can be overwhelming. All efforts should be made to facilitate this transition and to inspire confidence in the method. Once patients have performed the test, they must record their results. A calendar may function as both a testing schedule and a place for recording results. The trainer must verify that the patient understands the following before leaving the clinic: how to use the instrument, the days and times to perform the test, where to write down results, and what to do with the information (i.e. PSM versus doctor or anticoagulation-based management).

The trainer should try to anticipate any problems and develop a plan to solve them. The trainer should not assume that patients remember everything they have been taught, even though they may seem to understand at the time. Patients should have a point person to call if they experience any problems.

Finally, the trainer must give patients the opportunity to express concerns and ask questions. It is also important for the trainer to reinforce the incentive identified by each patient and the trainer at the beginning of the session. A transitional period is appropriate, during which patients perform PST measurements once a week with comparison testing carried out by the physician. This allows for the evaluation of the results of patients compared with the results of professionals and verification of proper functioning of the device, and addresses patient questions. Once patients are placed on the PST program, INR determinations should be supplemented with clinic visits every six to 12 months. The implementation of PST may seem daunting; however, multiple companies assist patients in obtaining these devices. Table 3 lists these companies and contact information, as well as the devices the companies support.

References

  1. Budnitz DS, Pollock DA,Weidenbach KN, et al., National surveillance of emergency department visits for outpatient adverse drug events, JAMA, 2006;296:1858–65.
    Crossref | PubMed
  2. Ansell JA, Hirsh J, Hylek E, et al., The pharmacology and management of the vitamin K antagonists, Chest, 2008; in press.
  3. Bernardo A, Experience with patient self-management of oral anticoagulation, J Thromb Thrombolysis, 1996;2:321–5.
    Crossref
  4. Van den Besselaar AM, Breddin K, Lutze G, et el., Multicenter evaluation of a new capillary blood prothrombin time monitoring system, Blood Coagul Fibrinolysis, 1995;6(8):726–32.
    Crossref | PubMed
  5. Kaatz SS, White RH, Hill J, et al., Accuracy of laboratory and portable monitor International Normalized Ratio determinations: comparison with a criterion standard, Arch Inter Med, 1995:155:1861–7.
    Crossref | PubMed
  6. McCurdy SA, White RH, Accuracy and precision of a portable anticoagulation monitor in a clinical setting, Arch Intern Med, 1992;152:589–92.
    Crossref | PubMed
  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;153:1441–7.
    Crossref | PubMed
  8. Lucas FV, Duncan A, Jay R, et al., A novel whole blood capillary technique for measuring prothrombin time, Am J Clin Pathol, 1987;88:442–6.
    Crossref | PubMed
  9. Yano Y, Kambayashi, Murata K, et al., Bedside monitoring of warfarin therapy by a whole blood capillary coagulation monitor, Thromb Res, 1992;66:583–90.
    Crossref | PubMed
  10. Weibert RT, Adler DS, Evaluation of a capillary whole blood prothrombin time measurement system, Clin Pharm, 1989;8:864–7.
    PubMed
  11. Rose VL, Dermott SC, Murray BF, et al. Decentralized testing for prothrombin time and activated partial thromboplastin time using a dry chemistry portable analyzer, Arch Pathol Lab Med, 1993;117:611–17.
    PubMed
  12. Fabbrini N, Messmore H, Balbale S, et al., Pilot study to determine use of a TAS analyzer in an anticoagulation clinic setting (abstract), Blood, 1995;86:869a.
  13. Ansell JA, Zweig S, Meyer B, et al., Performance of the AvocetPT prothrombin time system, Blood, 1998;9:112b.
  14. Gosselin R, Owings JT, White RH, et al., A comparison of point-of-care instruments designed for monitoring oral anticoagulation with standard laboratory methods, Thromb Haemost, 2000;83:698–703.
    PubMed
  15. Van den Besselaar AM, A comparison of INRs determined with a whole blood prothrombin time device and two international reference preparations for thromboplastin, Thromb Haemost, 2000;84:410–12.
    PubMed
  16. Kitchen S, Preston FE, Monitoring oral anticoagulant treatment with the TAS near patient test system: comparison with conventional thromboplastins, J Clin Pathol, 1997;50:951–6.
    Crossref | PubMed
  17. Douketis JD, Lane A, Milne J, et al., Accuracy of a portable international normalization ratio monitor in outpatients receiving long-term oral anticoagulant therapy: comparison with a laboratory reference standard using clinically relevant criteria for agreement, Thromb Res, 1998:92:11–17.
    Crossref | PubMed
  18. Cosmi B, Palareti G, Moia M, et al., Accuracy of a portable prothrombin time monitor (CoaguChek) in patients on chronic oral anticoagulant therapy, Thromb Res, 2000;100:279–86.
    Crossref | PubMed
  19. Earp B, Hambleton J, Spencer F, et al., Accuracy and precision of the LifeScan INR monitor in anticoagulation clinics, J Thromb Thrombolysis, 2001;12:109.
  20. Oral Anticoagulation Monitoring Study Group, Prothrombin measurement using a patient selftesting system, Am J Clin Pathol, 2001;115:280–87.
  21. Oral Anticoagulation Monitoring Study Group, Point-of-care prothrombin time measurement for professional and patient selftesting use, Am J Clin Pathol, 2001;115: 288–96.
    Crossref | PubMed
  22. Andrew M, Marzinotto V, Adams M, et al., Monitoring of anticoagulant therapy in pediatric patients using a new microsample PT device, Blood, 1995; 86:863a.
  23. Cachia PG, McGregor E, Adlakha S, et al., Accuracy and precision of the TAS analyzer for near-patient INR testing by non-pathology staff in the community, J Clin Pathol, 1998;51: 68–72.
    Crossref | PubMed
  24. Murray ET, Greaves M, INRs and point-of-care testing, BMJ, 2003;327:5–6.
    Crossref | PubMed
  25. Jennings I, Luddington RJ, Baglin T, Evaluation of the Ciba-Corning Biotrack 512 coagulation monitor for the control of oral coagulation, J Clin Pathol, 1991;44:950–53.
    Crossref | PubMed
  26. Tripodi A, Arbini AA, Chantarangkul V, et al., Are capillary whole blood coagulation monitors suitable for the control of oral anticoagulant treatment by the international normalized ratio?, Thromb Haemost, 1993;70:921–4.
    PubMed
  27. Beythe RJ, Quinn L, Landefeld C, A multicomponent intervention to prevent major bleeding complications in older patients receiving warfarin, Ann Intern Med, 2000;133:687–95.
    Crossref | PubMed
  28. Kortke H, Korfer R, International normalized ratio self-management after mechanical heart valve replacement: is an early start advantageous?, Ann Thorac Surg, 2001;72:44–8.
    Crossref | PubMed
  29. Watzke HH, Forberg E, Svolba G, et al., A prospective controlled trial comparing weekly self-testing and self-dosing with the standard management of patients on stable oral anticoagulation, Thromb Haemost, 2000;83:661–5.
    PubMed
  30. Menendez-Jandula B, Souto JC, Oliver A, et al., Comparing self-management of oral anticoagulant therapy with clinic management, Ann Intern Med, 2005;142:1–10.
    Crossref | PubMed
  31. Fitzmaurice DA, Murray ET, Gee KM, et al., J Clin Path, 2002;55:845–9.
    Crossref | PubMed
  32. White RH, McCurdy A, Marensdorff H, et al., Home prothrombin time monitoring after the initiation of warfarin therapy: a randomized, prospective study, Ann Intern Med, 1989;111: 730–37.
    Crossref | PubMed
  33. Kaatz S, Elston-Lafata J, Gooldy S, Anticoagulation therapy home and office monitoring evaluation study, J Thromb Thrombolysis, 2001;12:111.
  34. Sidhu P, O’Kane HO, Self-managed anticoagulation: results from a two-year prospective randomized trial with heart valve patients, Ann Thorac Surg, 2001;72:1523–7.
    Crossref | PubMed
  35. Sunderji R, Gin K, Shalansky K, et al., Canad J Cardiol, 2004;20:1117–23.
    PubMed
  36. Voller H, Glatz J, Taborski U, et al., Zeitschrift fuer Kardiologie, 2005;94:182–6.
    Crossref | PubMed
  37. Kahn TI, Kamali F, Kesteven P, et al., The value of education and self-monitoring in the management of warfarin therapy in older patients with unstable control of anticoagulation, Br J Haematol, 2004;126: 557–64.
    Crossref | PubMed
  38. Poller L, Keown M, Chauhan N, et al., European concerted action on anticoagulation: multicentre international sensitivity index calibration of two types of point-of-care prothrombin time monitor systems, Br J Haematol, 2002;116:844–50.
    Crossref | PubMed
  39. Horstkotte D, Piper C, Wiemer M, et al., Improvement of prognosis by home prothrombin estimation in patients with life-long anticoagulation therapy, Eur Heart J, 1996;17:230.
  40. Sawicki PT, A structured teaching and selfmanagement program for patients receiving oral anticoagulation: a randomized controlled trial: working group for the study of patient selfmanagement of oral anticoagulation, JAMA, 1999;281:145–50.
    Crossref | PubMed
  41. Fitzmaurice DA, Murray ET, Gee KM, et al., J Clin Pathol, 2002;55:845–9.
    Crossref | PubMed
  42. Heneghan C, Alonso-Coello P, Garcia-Alamino JM, et al., Self-monitoring of oral anticoagulation: a systematic review and meta-analysis, Lancet, 2006;367:404–11.
    Crossref | PubMed
  43. Christensen TD, Self-management of oral anticoagulant therapy: a review, J Thromb Thrombolysis, 2004;18(2):127–43.
    Crossref | PubMed