Clin Chem Lab Med 2016; aop

Mini Review

Doris Barcellona, Lara Fenu and Francesco Marongiu*

Point-of-care testing INR: an overview

DOI 10.1515/cclm-2016-0381 secondary antithrombotic prophylaxis in venous throm-
Received May 1, 2016; accepted September 15, 2016 boembolism, atrial fibrillation and in cardiac mechani-
cal valves [1]. The mechanism of action is to block the
Abstract: Oral anticoagulant therapies with the anti-
enzyme epoxide reductase that normally brings back
vitamin K drugs (AVK), warfarin, acenocoumarol and
the vitamin K epoxide (coming from having driven car-
phenprocoumon, are employed in primary and sec-
boxylation) to its reduced form, the only one capable of
ondary anti-thrombotic prophylaxis in patients with
inducing carboxylation of the Gla-protein residues. In
venous thromboembolism, atrial fibrillation and cardiac
this manner the carboxylated Gla-residues can bind Ca
mechanical valves. However, a monitoring test such as
ions which are essential for the coagulability of the four
the International Normalized Ratio (INR) is required. The
vitamin K dependent factors of the coagulation cascade
periodic monitoring of this therapy entails discomfort for
(II, VII, IX and X) on the phospholipid membranes [2]. As
the patients. Telemedicine and telecare can provide sig-
AVK induce a coagulopathy inhibiting the function of four
nificant aid in the management of this therapy allowing
vitamin K-dependent factors, a monitoring test such as the
patients to perform the test at home or anywhere else with
prothrombin time is required. The test developed by Quick
a portable device, i.e. point-of-care testing (POCT), and to
in 1935 [3] has been expressed as a percentage of activity
send the result to a thrombosis (TC) via web. Patients can
for many years but results have differed greatly between
receive dose adjustment sent back by the TC. The effective-
laboratories because of the diversity of the reagent used,
ness of this type of management is equal or superior to
i.e. thromboplastin (tissue factor), which is the trigger of
the traditional AVK monitoring in terms of hemorrhagic
the coagulation process, to be added along with calcium
and thrombotic events. Analysis of the costs with a hori-
to the plasma sample. In 1983, Kirkwood developed a
zon of 10 years reveals that both self-testing and self-man-
system called the International Normalized Ratio (INR)
agement are cost-effective. The aim of this overview is to
which was intended to harmonize the results between the
describe the pros and cons of the use of POCT as an alter-
different reagents [4]. The therapeutic range is consid-
native in the monitoring of AVK. In particular, descrip-
ered optimal if INR values falls within 2.0 and 3.0 for most
tion of the POCT, decentralization, quality of the therapy,
indications to AVK treatment [1]. It is therefore clear that
safety and costs will be examined.
for the duration of therapy, often lifelong, patients must
Keywords: anti-vitamin K antagonists; bleeding; Inter- undergo these periodic checks, ideally every 3–4 weeks or
national Normalized Ratio (INR); point-of-care testing even less. The monitoring of anticoagulation therapy can
(POCT); self-management; self-testing; thromboembolism. be conducted by thrombosis centers (TC), general practi-
tioners or the patients themselves. The periodic monitor-
ing of this therapy entails discomfort for the patients, the

Introduction TC are often very crowded and the general practitioner is

For the last 60  years oral anticoagulant therapies with
the anti-vitamin K (AVK) drugs, warfarin, acenocoumarol
and phenprocoumon have been used for primary and
*Corresponding author: Francesco Marongiu, Head of the Internal
Medicine and Haemocoagulophaties Unit, University of Cagliari,
Cagliari, Italy, Phone: +390706754188,
E-mail: marongiu@medicina.unica.it
Doris Barcellona and Lara Fenu: Department of Medical Sciences
“Mario Aresu”, University of Cagliari, Cagliari, Italy
not always able to manage this type of therapy. Further,
patients who perform self-management, i.e. the autono-
mous adjustement of the anticoagulant dosage after
having carried out INR, have obvious difficulties in the
case of bleeding, even if minor, taking interfering drugs,
preparation for surgery, etc. Portable devices, i.e. point-
of-care testing (POCT) can provide significant aid in the
management of this therapy because it allows patients to
perform the test at home or anywhere else with the possi-
bility to send the result to a TC via the Internet. In this way
the patients can receive the dose adjustment sent back by
the TC. The aim of this overview is to describe the pros and

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2      Barcellona et al.: Point-of-care testing INR
cons of this monitoring system as an alternative method
to monitoring AVK. In particular, the description of POCT,
decentralization and quality of the therapy, safety and
costs will be examined in the following sections.
Technology issues
The use of POCT for the management of anticoagulant
therapy with AVK was taken into consideration for the
first time at the end of the 1980s in the USA [5]. In recent
years their use has received more and more widespread
acclaim in Europe as well, where clinical studies con-
ducted in Germany [6], Austria [7], the Netherlands [8] and
Italy [9, 10] have shown that this type of management is
as effective as the monitoring of the AVK by means of INR
performed at the TC by venous blood sampling. The POCT
INR offers some advantages, such as: the ease of use, the
performance of the test on capillary blood in patients
with difficult venous access, the ability to quickly obtain
the INR value and possibly, through the decentralization
of the management, a reduction in the number of con-
trols that the patient would perform at the TC. POCT INR
involved in clinical studies and their methodologies are:
CoaguChek XS (Electrochemical detection of thrombin
activity, Roche Diagnostics, Basel, Switzerland), INRatio 2
(Electrochemical detection of changes in impedance Alere
Inc., San Diego, CA, USA), the ProTime Microcoagulation
system (stops blood flow through a capillary channel,
International Technidyne Corporation, Nexus Dx, Edison,
NJ, USA) and SmartCheck INR (electromechanically clot
detection by a metal disk which oscillates within a mag-
netic field, Unipath, Bedford, UK). In general, the accu-
racy of POCT to determine INR values in patients treated
with AVK is considered good in the scientific literature [11,
12]. In fact, it is possible to calibrate these devices accord-
ing to the model of the World Health Organization as dem-
onstrated several years ago by Tripodi and colleagues [13].
The coefficient of variation (CV) of these devices shows
values ranging from 1.4% to 8.4% depending on the differ-
ent kinds of POCT studied [12]. One of the biggest problems
is represented by the quality control of POCT. In clinical
practice the performance of the individual POCT INR is
evaluated through an internal quality control provided
by the manufacturer. However, this system does not allow
us to determine the accuracy of the test that requires an
external quality control (EQA). In this regard, a commonly
proposed method is the comparison of the INR values
obtained with the POCT system with the coagulometers of
the central laboratory of the hospital [11, 14]. The results
of the INR provided by the POCT are considered reliable
when the difference with the INR values provided by the
reference laboratory coagulometer does not exceed ± 0.5
INR units. The other EQC is to use a set of five lyophilic
plasmas with INR certification which currently represents
the best way to evaluate any inaccuracies of the instru-
ment, even if it requires logistic organization of the TC
and dedicated funds. An important study by Stavelin et al.
[15] dealing with EQA for POCT INR performed in Europe,
showed that there are many European countries that do
not provide this service while others performed EQA using
lyophilized samples with unknown target values. EQA is
also recommended by the UK NEQAS organization, which
has run a large program for POCT INR testing, inviting
users of these devices to regularly participate in an inde-
pendent external testing program [16]. The performance
of the POCT is considered acceptable when the INR values
obtained show a difference of 15% or less compared to cer-
tified INR values. The external quality control should be
performed at the TC twice a year or whenever the patient
changes the lot of test strips [17]. This statement is based
on a study which investigated the performance of 95 Coa-
gucheck S assigned to 99 anticoagulated patients at home
on a quarterly basis [18]. This experience demonstrated
significant variability among the different lots of strips
used. Lots with differences higher than 10% in terms
of ± 0.5 INR Units at the first, second and third controls
were 16%, 20.8% and 61%, respectively. Anti­coagulated
patients should therefore periodically bring their portable
coagulometers and test strips to a reference TC to check
their performance against the coagulometer of the TC and
with lyophiled plasmas wth ceritified INR. This procedure
should be carried out when the lot of strips have to be
changed.
POCT INR and decentralization of
AVK management
One of the advantages of the use of POCT INR is the pos-
sibility to monitor the AVK more closely as these devices
allow patients to perform the test at home or in peripheral
districts such as general practitioner’s offices, outpatient
clinics and pharmacies thus avoiding going frequently to
their own TC. Decentralization of AVK management can be
carried out in different ways: (a) patients who are referred
to peripheral health districts, (b) patients who perform
self-testing INR followed by the adjustment of the antico-
agulant dosage by a physician, (c) patients who perform
self-management of the therapy.
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The health districts
This type of decentralization requires patients to go to
peripheral districts (outpatient clinics, pharmacies or
general practitioners’ offices) where INR can be performed
through the use of a POCT. The district caregiver (doctor,
nurse or pharmacist) is involved not only in testing INR
but also in collecting useful information for a correct dose
adjustment of the therapy (incorrect or missed prescribed
dose, adverse events, interfering drugs, planned surgery
or invasive procedures). Transmission of INR and anam-
nestic information to the TC is carried out via the I­ nternet
through dedicated software. The TC doctors process the
therapy, establish the date of the next control and retrans-
mit the data to the district. This model of decentralization
requires the caregiver to be properly trained by the TC staff
in the principles of the test (PT INR), the optimal execution
of capillary blood sampling, to minimize the variability of
the results, and in the use of the POCT itself. Education
should also be provided on the use of the software which
connects the district to the TC and on the need to submit
the portable coagulometer to both an internal and EQC.
The latter should be performed at least twice a year or
whenever the lot of the strips needs to be changed. Quality
checks must be performed and are the direct responsibility
of the TC laboratory. Studies in the literature report how a
TC can be effectively reorganized by adopting this type of
decentralization [19, 20]. POCT INR are also used in other
different settings such as pharmacies, emergency depart-
ment and general practitioners. In these cases POCT INR
are used without Internet support [21, 22].
Patients in self-testing
Patients in self-testing is a decentralization of therapy
with AVK in which the patient or someone else (rela-
tives or friends) performs the PT INR at home through the
use of the POCT. Also in this case, the test result and the
patient’s history are transmitted to the TC via web. In this
type of decentralization it is necessary to provide educa-
tional courses that must be followed by the patient, or by
a spouse or relative, individually. It is important to evalu-
ate the cognitive capacity of who will perform the INR,
objectively measurable through clinically validated tests
[23]. At the end of the educational course, the patient
or whoever else must demonstrate competence in the
measurement of INR by POCT and in the transmission
of both the INR result and the anamnestic information.
A recently published study demonstrated that, even with
Barcellona et al.: Point-of-care testing INR      3
little training, highly educated people (most of them pro-
fessionals or university educated) on oral anticoagulant
therapy with AVK can self-monitor their INR. Interest-
ingly, TTR was shown to improve with age [24]. Patients
or their relatives that are not able to perform the test and
transmit the data or that are not sufficiently motivated
are to be excluded from this type of management. The
responsibility of the training and execution of quality
controls falls on the TC twice a year, or at the change in
the number of test strips, and it must perform an assess-
ment of the performance of the POCT [17, 18]. The safety
and efficacy of this type of AVK monitoring is confirmed
by the results of our study on the management of a group
of 114 patients in self-testing at home through a telemedi-
cine system [10]. We compared patients being monitored
at home by self-testing using a POCT INR and telemedi-
cine support with a previous period of conventional
monitoring at a TC. Patients were divided into two groups
on the basis of TTR during conventional care: the unsta-
ble group had TTR < 70% and the stable group had TTR
> 70%. The unstable group showed a significant increase
in TTR with home monitoring: 63%–68% (p < 0.001)
while in the stable group there was no significant change
(77%–75%).
Patients in self-management
In this type of decentralization of management, the
patients perform their own tests through the POCT
auto­nomously, they process the therapeutic scheme
through the use of a dedicated algorithm. Also, in this
type of monitoring, it is essential to evaluate the cogni-
tive capacity of who will perform the therapy (patient or
joint) and organize educational courses that instruct the
patient about the correct use of the portable coagulom-
eter and the elaboration of the dosage of the anticoagu-
lant drug. Patients should have an algorithm that has
been discussed and approved by the TC so as to allow
for a more standardized management of the therapy as
possible. The patients are responsible for the proper
application of the algorithm, but the TC will ensure con-
tinuous assistance both in terms of quality control of the
POCT and as regards changes in the dosage or suspen-
sion of the AVK in conditions such as adverse events,
surgical operations, invasive procedures or whenever the
patient requests it. A study [9] has shown that the use of
this type of decentralization of therapy is safe and effec-
tive when the patient is properly selected, trained and
assisted by the TC.
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4      Barcellona et al.: Point-of-care testing INR
POCT INR and time spent in the
therapeutic range (TTR)
TTR is a direct measure of the quality of the management
of AVK therapy and it can be calculated by different ways
[25] but the most commom method is that of Rosendaal
et al. [26]. Even in the recent clinical trials on the new anti-
coagulants, TTR has been employed to verify the quality
of the oral anticoagulation in the control groups, i.e. that
of patients treated with warfarin [27]. An optimal manage-
ment of the anticoagulant therapy with AVK requires a
TTR percentage  ≥ 70% [28]. TTR is an important parameter
as it negatively correlates with hemorrhagic and/or throm-
boembolic adverse events [29]. Recently, Senoo and Lip
[30] investigated adverse outcomes in 2292 patients with
atrial fibrillation taking warfarin or acenocoumarol in the
AMADEUS trial. TTR was found to be negatively correlated
with relevant bleeding and stroke. One meta-analysis [31]
shows an increase in the TTR of 8% in patients who carry
out self-monitoring or self-management of therapy (73%,
95% CI 69%–76%) vs. the control care group (62%, 95% CI
59%–65%). An analysis of 17 studies showed that the TTR
in patients both in self-testing and self-management was
4.86% higher than in controls [11].
Safety
The safety of the use of portable automated coagulometers
by patients who carry out self-testing of INR or the self-
management of therapy with AVK has been the subject
of several randomized clinical trials and meta-analysis
published in recent years [31–34]. The aim was to assess
the incidence of adverse events, thromboembolism, major
bleeding and mortality in patients able to perform both
the self-testing and the self-management of the therapy
and in patients undergoing traditional monitoring of
treatment with AVK. The results of a meta-analysis show
a significant reduction in the incidence of thromboem-
bolic events, about 50%, in patients who carried out the
INR self-testing or self-management of treatment, com-
pared with traditional monitoring. However, with regard
to the incidence of bleeding complications, most of the
studies indicate that there is no significant reduction of
events when the two monitoring systems are compared,
with the single exception of the work by Wells et al. [31]
that reported a reduction in hemorrhages up to 49%. In
particular, in their systematic review and meta-analysis
of single patient data, Heneghan et  al. [34] reported an
important reduction in thrombotic events in patients
younger than 55 years (HR 0.33, 95% CI 0.17–0.66), as in
those with mechanical heart valves (HR 0.52, 95% CI 0.35–
0.77). Finally, in a recent systematic review [35] including
28 randomized controlled trials (8763 participants), both
self-management and self-testing were found to be as
safe as traditional care in terms of major bleeding events
(RR = 1.08, 95% CI 0.81–1.45, p = 0.690, and RR = 0.99, 95%
CI 0.80–1.23, p = 0.92, respectively). Surprisingly, self-
management was associated with less thromboembolism
(RR = 0.51, 95% CI 0.37−0.69) and with a trend towards a
significant reduction in all-cause mortality (RR = 0.68,
95% CI 0.46–1.01) compared to conventional care. It is dif-
ficult to explain these findings. Possibly, patients on self-
management are more accurate and careful both in the
self-adjustment of the anticoagulant dosage and in follow-
ing the algorithm schema. It is also possible that people
in self-management felt themselves more motivated to
follow recommendations and the rules for the control of
the therapy. However, these results, coming from con-
trolled trials, should be confirmed in real life studies.
Nevertheless, the work by Matchar et al. [36] shows that
the average annual increase of tests performed was equal
to 22–24 in patients who perform self-testing INR as com-
pared to patients receiving the usual monitoring with INR
performed with a venous blood sampling. This study also
demonstrates that patient satisfaction and quality of life
are significantly greater in those who carry out self-deter-
mination of the INR compared to patients who are moni-
tored in the conventional maanner.
Costs and limits
POCT INR and reactive strips are expensive ranging from
about €500 to €700 and €2–€3, respectively. Reimburse-
ment, as with other chronic diseases such as diabetes
mellitus, is not allowed by the National Health System,
at least in Italy. However, a systematic analysis in the UK
[37] of the costs with a horizon of 10  years reveals that
both self-testing and self-management are cost-effective.
Total health care costs over 10  years were £7324 with
conventional care and £7326 with self-monitoring with
a quality adjusted life year (QALY) of about 0.03. In par-
ticular, selfmonitoring seems to have a high probability
of being cost-effective when compared with conventional
care resulting in an acceptable willingness-to-pay thresh-
old of £20,000 per QALY gained. A contraindication to the
use of POCT INR seems to be a high hematocrit (> 50%).
Although there are no reports in the literature supporting
this statement the manufacturers, in general, discourage
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the use of POCT in this condition. Another contraindica-
tion to the use of POCT may be anti-phospholipid syn-
drome (APS). A study of ours demonstrated that the use
of a POCT INR (Coaguchek XS, Roche Diagnostics, Basel,
Switzerland) in patients with a triple positivity for anti-
phospholipid antibodies (lupus anticoagulant, anti-car-
diolipin and anti-beta 2-glycoprotein I antibodies IgG and
IgM) may increase the thrombotic risk in patients with
APS as this device overestimates INR for values between
2.0 and 3.0 [38].
POCT and the new anticoagulants
One wonders whether these devices should still be con-
sidered today when new anticoagulants are present on
the market and do not require determination of INR [36].
However, not all patients with an indication for oral
anticoagulant are candidates for the new anticoagu-
lants as they are not recommended in cases of mechani-
cal heart valves, severe renal failure because of the risk
of accumulation and gastrointestinal disease because
these new anticoagulants can induce bleeding more
than AVK [39]. Nevertheless, even to those patients for
whom the new anticoagulants may be indicated, doctors
should always offer POCT INR after thorough and inde-
pendent counseling.
Conclusions
POCT INR are reliable devices that can be safely used to
monitor oral anticoagulation with AVK. They are easy
to use and can reduce the patient discomfort in having
to reach a TC or other health venue for the INR deter-
mination. An undeniable advantage is to use POCT INR
at home or anywhere else when an Internet connection
is available. Telemedicine can be very helpful in this
regard. Not all patients are good candidates, however.
Only motivated patients who demonstrate they have
properly learnt how to use the device for self-testing or
self-management can afford this particular method of
AVK monitoring. This is what has been recommended by
the American College of Chest Physicians (ACCP) in 2012
[35]. Periodic checks of the performance of POCT should
be planned at the TC especially when the lots of strips are
to be changed.
Acknowledgments: We thank Mr. Barry Mark Wheaton for
his editing assistance.
Barcellona et al.: Point-of-care testing INR      5
Author contributions: All the authors have accepted
responsibility for the entire content of this submitted
manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played
no role in the study design; in the collection, analysis, and
interpretation of data; in the writing of the report; or in the
decision to submit the report for publication.
References
1. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palar-
eti G, et al. Oral anticoagulant therapy: antithrombotic therapy
and prevention of thrombosis, 9th ed: American College of Chest
Physicians evidence-based clinical practice guidelines. Chest
2012;141:e44S–88S.
2. Stenflo J, Fernlund P, Egan W, Roepstorff P. Vitamin K dependent
modifications of glutamic acid residues in prothrombin. Proc
Natl Acad Sci USA 1974;71:2730–33.
3. Quick AJ. The prothrombin in hemophilia and in obstructive
jaundice. J Biol Chem 1935;109:73–4.
4. Kirkwood TB. Calibration of reference thromboplastins and
standardization of the prothrombin time ratio. Thromb Haemost
1983;49:238–44.
5. Ansell J, Holden A, Knapic N. Patient self-management of oral
anticoagulant guided by capillary (fingerstick) whole blood
prothrombin times. Arch Intern Med 1989;149:2509–11.
6. Taborski U, Muller-Berghaus G. State-of-the-art of patient self-
management for control of oral anticoagulation. Semin Thromb
Hemost 1999;25:43–7.
7. Watzke HH, Forberg E, Svolba G, Jimenez-Boj E, Krinninger B. A
prospective controlled trial comparing weekly self-testing with
standard management of patients on stable oral anticoagula-
tion. Thromb Haemost 2000;83:661–5.
8. Gadisseur AP, Breukink-Engbers WG, van der Meer FJ, van den
Besselaar AM, Sturk A, Rosendaal FR. Aanticoagulant therapy
through patient self-management and management by special-
ized anticoagulation clinics in the Netherlands: a randomized
clinical trial. Arch Int Med 2003;163:2639–46.
9. Cosmi B, Palareti G, Carpanedo M, Pengo V, Biasiolo A, Ram-
pazzo P, et al. Assessment of patient capability to self-adjust
oral anticoagulant dose: a multicentre study on home use of
portable prothrombin time monitor (COAGUCHEK). Haemato-
logica 2000;85:826–31.
10. Barcellona D, Fenu L, Cornacchini S, Marongiu F. Telemedicine
can improve the quality of oral anticoagulation using port-
able devices and self-testing at home. J Telemed Telecare
2013;19:298–301.
11. Health Quality Ontario. Point-of-care international normal-
ized ratio (INR) monitoring devices for patients on long-term
oral anticoagulation therapy. Ont Health Technol Assess Ser
2009;9:1–114.
12. Christensen TD, Larsen TB. Precision and accuracy of
­point-of-care testing coagulometers used for self-testing and
Brought to you by | Tufts University
Authenticated
Download Date | 10/20/16 9:45 AM
6      Barcellona et al.: Point-of-care testing INR
s­ elf-management of oral anticoagulant therapy. J Thromb Hae-
most 2012;10:251–60.
13. Tripodi A, Arbini AA, Chantarangkul V, Bettega D, Mannucci PM.
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.
14. Sølvik UØ, Stavelin A, Christensen NG, Sandberg S. External
quality assessment of prothrombin time: the split-sample model
compared with external quality assessment with commercial
control material. Scand J Clin Lab Invest 2006;66:337–49.
15. Stavelin A, Meijer P, Kitchen D, Sandberg S. External quality
assessment of point-of-care international normalized ratio (INR)
testing in Europe. Clin Chem Lab Med 2011;50:81–8.
16. Kitchen S, Kitchen DP, Jennings I, Woods TA, Walker ID, Preston
FE. Point-of-care international normalized ratios: UK NEQAS
experience demonstrates necessity for proficiency testing of
three different monitors. Thromb Haemost 2006;96:590–6.
17. Jespersen J, Poller L, van den Besselaar AM, van der Meer FJ,
Palareti G, Tripodi A, et al. External quality assessment (EQA) for
CoaguChek monitors. Thromb Haemost 2010;103:936–41.
18. Barcellona D, Fenu L, Cornacchini S, Marongiu F. Point-of-care
(POCT) prothrombin time monitors: is a periodical control of
their performance useful? Thromb Res 2009;123:775–9.
19. Pengo V. Monitoring oral anticoagulants: new strategies for an
emerging problem. Intern Emerg Med 2006;1:3–4.
20. Testa S, Alatri A, Paoletti O, Morstabilini G, Medagliani MA,
Denti N, et al. Reorganization of an anticoagulation clinic using
a telemedicine system: description of the model and preliminary
results. Intern Emerg Med 2006;1:24–9.
21. St John A. The evidence to support point-of-care testing. Clin
Biochem Rev 2010;31:111–19.
22. Goble JA, Rocafort PT. Point-of-care testing: future of
chronic disease state management? J Pharm Pract 2015:pii:
0897190015587696. [Epub ahaed of print].
23. Palareti G, Poggi M, Guazzaloca G, Savino A, Coccheri S. Assess-
ment of mental ability in elderly anticoagulated patients: its
reduction is associated with less satisfactory quality of treat-
ment. Blood Coag Fibrinol 1997;8:411–17.
24. Ward A, Tompson A, Fitzmaurice D, Sutton S, Perera R, Heneghan
C. Cohort study of anticoagulation self-monitoring (CASM): a
prospective study of its effectiveness in the community. Br J Gen
Pract 2015;65:e428–37.
25. Optimal Warfarin Management for the Prevention of Thrombo-
embolic Events in Patients with Atrial Fibrillation: A Systematic
Review of the Clinical Evidence [Internet]. Ottawa (ON): Cana-
dian Agency for Drugs and Technologies in Health, 2011. CADTH
Optimal Use Reports.
26. Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A
method to determine the optimal intensity of oral anticoagulant
therapy. Thromb Haemost 1993;69:236–39.
27. Schneeweiss S, Gagne JJ, Patrick AR, Choudhry NK, Avorn J.
Comparative efficacy and safety of new oral anticoagulants in
patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes
2012;5:480–6.
28. Dallalzadeh LO, Go AS, Chang Y, Borowsky LH, Fang MC, Singer
DE. Stability of high-quality warfarin anticoagulation in a
community-based atrial fibrillation cohort: the Anticoagulation
and Risk Factors in Atrial Fibrillation (ATRIA) Study. Am Heart
Assoc 2016;5:pii: e003482.
29. Wan Y, Heneghan C, Perera R, Roberts N, Hollowell J, Glasziou P,
et al. Anticoagulation control and prediction of adverse events
in patients with atrial fibrillation: a systematic review. Circ
Cardiovasc Qual Outcomes 2008;1:84–91.
30. Senoo K, Lip GY. Female sex, time in therapeutic range, and
clinical outcomes in atrial fibrillation patients taking warfarin.
Stroke 2016;47:1665–8.
31. Wells PS, Brown A, Jaffey J, McGahan L, Poon MC, Cimon K.
Safety and effectiveness of point-of-care monitoring devices in
patients on oral anticoagulant therapy: a meta-analysis. Open
Med 2007;1:e131–46.
32. Garcia-Alamino JM, Ward AM, Alonso-Coello P, Perera R,
Bankhead C, Fitzmaurice D, et al. Self-monitoring and self-man-
agement of oral anticoagulation. Cochrane Database Syst Rev
2010;4:CD003839.
33. Bloomfield HE, Krause A, Greer N, Taylor BC, MacDonald R,
Rutks I, et al. Meta-analysis: effect of patient self-testing and
self-management of long term anticoagulation on major clinical
outcomes. Ann Intern Med 2011;154:472–82.
34. Heneghan C, Ward A, Perera R. Self-monitoring of oral antico-
agulation: systematic review and meta-analysis of individual
patient data. Lancet 2012;379:322–34.
35. Sharma P, Scotland G, Cruickshank M, Tassie E, Fraser C,
Burton C, et al. Is self-monitoring an effective option for
people receiving long-term vitamin K antagonist therapy?
a systematic review and economic evaluation. BMJ Open
2015;5:e007758.
36. Matchar DB, Jacobson A, Dolor R, Edson R, Uyeda L, Phibbs CS,
et al. Effect of home testing of international normalized ratio on
clinical events. N Engl J Med 2010;363:1608–20.
37. Meyer S, Frei CR, Kelly RD. Impact of a new method of warfarin
management on patient satisfaction, time and cost. Pharmaco-
therapy 2013;33:1147–55.
38. Barcellona D, Fenu L, Vannini ML, Piras M, Marongiu F. Antiphos-
pholipid syndrome patients: the performance of Coaguchek
XS in the monitoring of Vitamin-K Antagonists. Thromb Res
2012;129:e168–70.
39. Pengo V, Crippa L, Falanga A, Finazzi G, Marongiu F, Moia M,
et al. Phase III studies on novel oral anticoagulants for stroke
prevention in atrial fibrillation: a look beyond the excellent
results. J Thromb Haemost 2012;10:1979–87.
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