BLOOD
COAGULATION
POINT OF CARE INR TESTING MEETING
10th November 2009
Conference Centre
Mercure St Paul’s Hotel,
ABSTRACTS
WHICH DEVICES ARE
AVAILABLE: ADVANTAGES AND DISADVANTAGES
Chris Gardiner,
Monitors intended for patient self-testing. These use
capillary whole blood obtained from a fingerprick. The sample volume is
generally small (<30µL) and there are few operator dependent steps. Result
storage is limited and there is no facility for positive patient
identification. The CoaguChek XS, Hemosense INRatio2 and ITC Protime are all
intended for patient self-testing.
Monitors intended for professional use are larger and more
complex. Tests other than PT/INR may be available. These monitors should allow
patient identification to be recorded and stored with the test result and have
much larger data storage capacity. The Hemochron Jr. Signature+, Thrombi-Stat CD501WB, CoaguChek XS Plus, I-Stat and Thrombotrack are all intended for
professional PoCT use.
Since the introduction of POCT PT/INR monitors in the
1990s the sample volume required for testing has diminished, as have both the
size and costs of instruments. Initially, these instruments were unreliable
with considerable variation of the INR within the overall therapeutic range,
but with the development of new technologies and quality control procedures,
their reliability has considerably improved.
There are several methods of clot detection currently
employed by POCT PT/INR monitors. These may be broadly described as
electro-mechanical, optical, electrochemical or photo-reflection. The method of
clot detection can dictate the type of quality control preparations that may be
used. Optical detection methods that rely on the presence of red blood cells
and some electrochemical methods cannot be used with lyophilised plasma QC
preparations.
The type of coagulation monitor purchased will depend very
much on who is going to use the device and the setting in which it will be
used. Coagulation monitors developed for patient self-monitoring are simple to
use and have few operator dependent steps. Indeed, in his review of pathology
services, Lord Carter recommended that devices for patient self-testing “must
be safe, accurate – and foolproof”. These instruments should display results in
an easy to read format and require minimal data storage.
Devices for professional use may have more user definable
steps and may require the operator to have additional training and skills. In
an anticoagulant clinic setting, additional patient identification and data
management features are usually desirable. All coagulation monitors intended
for professional use should have an interface, which allows connection to a
computer or printer, while others allow connection to anticoagulant dosing
programs, data management packages or the hospital information systems. The
connectivity of a POCT device may be a major factor in the selection process. Little
or no connectivity may be required for self-monitoring patients. In contrast,
if the POCT device is to be used in a hospital anticoagulation clinic or
primary care practice, some data management functions will be required. The
degree of connectivity and the precise data management functions will
ultimately depend upon the IT system used by the individual clinic.
Prior to 2008, PoCT devices for monitoring anticoagulation
were formally evaluated by the MDA, MHRA, DES or PaSA. The evaluations looked at safety, precision,
accuracy, safety, lot-to-lot variation and ease of use. Some of these
evaluations are still available on-line. However, any devices brought to the
While cost is an important variable in purchasing
decisions, so too are accuracy and ease
of use. In addition to cost information, purchasers should obtain information
about sample volume, patient identification, connectivity and quality control
options. This might include information about the extent to which each device
can meet the clinical requirements and the needs of patient groups for whom the
products are intended. One of the most important considerations is the
complexity of the device i.e., the number of user definable steps involved in
performing a test. Devices intended only for professional use are not suitable
for patient self-monitoring. The potential disadvantages of each option should
also be considered. It would be unwise to purchase a device which has not been
independently evaluated, unless the purchasing authority has the capacity to
perform a rigorous evaluation prior to use.
HOW TO GET RELIABLE RESULTS
OUTSIDE THE LABORATORY
Ellen Murray,
There is a dramatic increase in POC use outside laboratories partly due to NHS initiatives promoting the increased use of high street POC testing e.g. Healthy Heart campaign for pharmacists.
The quality of results performed by non laboratory staff is influenced by many factors including appropriate sample collection and handling; selection of a suitable technique; maintenance of up-to-date standard operating procedures and adequate records and reporting system for results.
The reliability of point of care results are assessed in laboratories by means of a Clinical Pathology Accreditation (CPA) inspection however the utilisation of POC devices outside the laboratory setting are not covered by the CPA regulatory authority.
So what guidelines are there to support POC use
outside the laboratory?
Guidelines for POC coagulometers were produced in 1995 by the BCSH. These guidelines provided a framework for local arrangements for POC testing for haematology tests incorporating secondary and primary care services.
More recently, the 2008 Independent Review of NHS Pathology Services in England, chaired by Lord Carter of Coles recommended that all providers of pathology services (including providers of point-of-care testing) should participate in clinical audit and other clinical governance activities, participate in relevant continuous professional development as part of maintaining their competence, be accredited in accordance with a national independent accreditation process and should have full participation in external quality assurance schemes.
BCSH guidelines were updated in 2008 advising a multidisciplinary POCT committee to support these recommendations. The POC committee should have a co-ordinator from a CPA accredited laboratory to take responsibility for all aspects of the service. Trainers from the committee will train, quality assure and ensure compliance and provide formal clinical supervision. Trainees should be awarded certificate of competency by the supervising laboratory and then be added to a list of authorised users. Ongoing retraining and updated assessment in place was also recommended.
What training is currently available? The National Centre for Anticoagulation Training is involved in university accredited certification which includes point of care training. The training involves clinical supervision and summative assessment, supervised placements at site, summative assessment based on agreed standards and benchmarks. This is undertaken over a six month period to ensure competency to run and manage an anticoagulation clinic. Some POC manufacturers also offer training of their specific devices either through formal training sessions or one to one training with a nurse educator.
What training is there for patients using POC devices?
Manufacturers supply DVDs and recommend clinical supervision for health care professional. Guidelines for patient self testing or management recommend setting bench marks for the safety and frequency of POC testing; assessing competence with dosage and adverse event procedure, and appropriate quality control.
In
summary, POC
testing utility is on the increase and used by a wide variety of health care
professionals and patients. There is an urgent need for accreditation to ensure
standardisation of performance. POC committees should be involved in: training and quality assurance procedures, issue
certificates of competence to operators based on those recommended by Carter
report and BCSH guidelines.
LABORATORY AND POINT OF
CARE INR RESULTS: WHICH TO BELIEVE?
Of
the many telephone and e-mails enquiries we receive at the
Initially
it is essential to establish a good rapport between the laboratory and the POC
centers so that any differences seen in results can be discussed and investigated. Where possible it is advisable to establish a
baseline relationship between the 2 methods by testing approximately 20 stable
patients with both methods. Once these data is available then if any change in
the relationship between the methods is seen a thorough investigation can be
performed. Secondly it is important to
establish whether there is a consistent bias between results rather than an
occasional discrepancy and for this thorough record keeping is important.
Quality control of both methods should be reviewed and any changes in batches
of POC test strips or laboratory reagent/ instrumentation should be taken into
consideration.
It
is important to remember that in the induction phase of warfarin therapy, in
unstable patients and patients who are over anticoagulated, comparison of INR
results between any 2 methods may differ causing confusion and resulting in
difficulty when dosing these patients.
In
a recent questionnaire completed by 810 POC centers 74% did send comparison
samples to the laboratory. The data in
figure 1 shows under what circumstances venous samples were sent to the
laboratory for testing. 49% of centers
that carried out venous comparison checks did so if the POC device gave a high
INR reading. Samples with INR results greater than 4.5 are likely to give a
different result with different methods (either between the laboratory and POC
or between 2 laboratory methods) due to the fact that the INR system has been
specifically designed to give agreement in samples within the therapeutic
range.
Finally
if a specific patient is showing discrepancy but this is not noted with other
patients it is important to test for Lupus anticoagulant. Patients who have Lupus anticoagulant can give
different INR results depending upon the reagent used for testing and it is
generally suggested that these patients are monitored by specialist hospital
centers.
Figure 1
MANAGEMENT OF THE OVER-ANTICOAGULATED PATIENT
Michael Makris,
Approximately 1-2% of the population are being treated
with warfarin at any one time. The major adverse event associated with their
use is bleeding and occurs in a major form at 1% per year and is fatal in 0.3%
per year. Risk factors for bleeding include elevated INR, older age,
uncontrolled hypertension, trauma and use of anti-platelet drugs. Although the
bleeding risk increases with a rising INR, partial reversal is only required
for patients with INR of >10.0 or those with INR of 6.0-10.00 and at high risk
of bleeding. When reversal within 24 hours is required, this is best achieved
with low dose oral vitamin K. When more rapid reversal is required, the vitamin
K should be given intravenously, in which case significant correction is seen
within 6-8 hours. For life-threatening bleeding, the best reversal agent is 4
factor prothrombin complex concentrate (PCC) which can completely correct the
INR within 5-10 minutes. Despite the clear evidence for the rapid efficacy of
PCC, many clinicians continue to use fresh frozen plasma (FFP). FFP only
partially corrects the INR and large volumes need to be administered. Some
centres, especially in the
All facilities managing patients on warfarin should have a
protocol for the management of patients with elevated INR or bleeding and
ideally this should be consistent with the 8th ACCP guidelines.
THIS HOUSE BELIEVES THAT
ORAL ANTICOAGULANT THERAPY IS BEST DELIVERED IN PRIMARY CARE
D Fitzmaurice,
University of Birmingham, UK
Background: The last
decade has seen an eclipse in the provision of oral anticoagulation
services, driven by the increased numbers of patients receiving warfarin
therapy, particularly for stroke prevention in atrial fibrillation. This, in
combination with technological advances which enable point of care INR
testing, has led to the provision of oral anticoagulation services in sites
outside the traditional hospital out-patients.
The debate: This house will provide evidence of the
therapeutic control provided within primary care based oral anticoagulation
clinics. The improvement in care is related to the holistic approach
provided in primary care compared to the production line service which is
necessarily provided in hospital due the sheer volume of numbers. If we take
diabetes as a comparator, it would seem sensible for the majority of
patients to be managed within a primary care setting, freeing up valuable
consultant time to manage the very difficult cases, for example patients
with antithrombin deficiency. Conclusion: Oral anticoagulation is best
delivered in primary care because it can be.
THIS HOUSE BELIEVES THAT ORAL
ANTICOAGULANT THERAPY IS BEST DELIVERED IN PRIMARY CARE: AGAINST I have been responsible for the delivery of long term oral anticoagulant
care to overall about 3,000 patients for the past 30 years. During this time there has been several changes in the various forms of
delivery of the anticoagulant services. In particular we now have
about 300 patients on long term self-testing/self- management using small
Point of Care Testing INR devices. Recently the local PCT’s (we deal
with about 6 major ones) have requested or rather demanded that the service
be re allocated to primary care. The main driver for this change was
because government policy has been directed to providing care away from the
hospital to be closer to the patient. Most general practitioners
wanted to offer this service because there was a fee to the practice per
patient per year. Generally speaking primary care is not interested in being involved in
delivering patient self-testing and self-management. There is also
serious problems about this change because of potential confusion when
patients are transferred back to primary care and when problems occur
regarding particularly high INR’s, frequent changes in INR, (the so called
brittle patient) and who was responsible for providing dosage advice at a
particular time. Many of the GP’s leave this service to their Practice
Nurse and although there are several excellent post graduate training
courses, many of the GP’s certainly in inner city London, do not have the
time or indeed interest to attend these courses on a regular fashion or for
their nurses to be suitably trained and commit to long term audit of the
success of their INR dosage and monitoring service. These general
practices are also demanding that the hospital offers a fast response help
line which essentially means that when they do not know what to do, they can
ring up the hospital or indeed send them to the A&E department who will then
bale them out. The main concern about this change to primary care is
that more patients could potentially be admitted with acute bleeding
problems with unacceptable increased period of times when they have high
INR’s. There is also problems about advice the patients should receive
when dental treatment or minor/ major surgical procedures are planned.
There are about a million patients in the UK on long-term oral anticoagulant
therapy. It is unclear whether general practice, particularly in inner
city areas are committed to providing a state of the art service to the
majority of these patients. In particular do they provide
regular internal/external QC procedures according to CPA regulations?
Is their INR dosage service linked to an appropriately tested IT system? There have been several research exercises performed from academic
centres of general practice, which have generally shown perfectly acceptable
results. However, results from clinical trials run by committed
medical practitioners never translate exactly into routine clinical
practice. The big fear is that by the mass transfer of patients to general
practice, cost cutting exercises will be made by the PCT’s, adequate
training and follow up assessment of the INR/Warfarin dosage systems will
not be properly maintained and the overall time in desired therapeutic range
will fall in particular with an increased risk of bleeding and thrombotic
complications.
ANTICOAGULATION IN ATRIAL FIBRILLATION Atrial
fibrillation, usually nonvalvular, is common in the older population (lifetime
risk 1 in 4), and increases the risk of stroke about five-fold (annual risk in
non-anticoagulated patients 5%). Most
of these strokes are thromboembolic, and 90% of these arise from the left atrial
appendage. Possible strategies to reduce
thromboembolic risk include rhythm control; percutaneous closure of the left
atrial appendage; antiplatelet therapy (aspirin or aspirin-clopidogrel) or
anticoagulant therapy (usually warfarin).
Warfarin is more effective than antiplatelet therapy (reducing risk in
randomized controlled trials, and also in prospective observational studies, by
about two-thirds). However, warfarin
also increases the risk of bleeding (including haemorrhagic stroke, which
reduces its net effect in stroke prevention); has a narrow therapeutic range;
and interacts with alcohol, some foods and other medications. Even with patient education and frequent INR
monitoring and dose adjustments, up to half of blood samples are outside the
therapeutic range and even expert centres achieve time-in-range results of only
65-70%. Audits
show that only about 50% of patients for whom current evidence-based clinical
practice guidelines recommend consideration for long-term warfarin receive it,
although there is some evidence that such guidelines increase rates of
appropriate prescription. Furthermore
there is wide variation in prescription practice, partly due to varying
perceptions by both physicians and patients on risks of thrombosis and bleeding. Physician-patient
decisions on warfarin can be assisted by stroke risk scores (e.g. SIGN, CHADS2,
NICE, ACCP). These scores assess risk of
thromboembolism according to clinical risk factors. Current research is assessing the additive
risk stratification of laboratory risk factors (e.g. fibrin D-dimer) and
clinical risk factors for intracranial bleeding. A recent large European study has shown that
computer-assisted dosing of oral anticoagulants is superior to doctor-dosing
for reducing the combination of thrombotic and haemorrhagic events in patients
with venous thromboembolism, but not in patients with atrial fibrillation;
however computer-assisted dosing is cost-effective. Preliminary results of randomized trials of
warfarin versus new oral anticoagulants are encouraging (e.g. the RE-LY study
of dabigatran, N Engl J Med 2009;361).
Such agents are effective in fixed doses, and may improve the percentage
of patients with atrial fibrillation who benefit from long-term
anticoagulation. DURATION OF ANTICOAGULATION
FOLLOWING FIRST VTE Optimal
anticoagulation for any indication or patient is that which provides most
benefit while causing least harm. In the context of 1st venous
thromboembolism (VTE) the primary benefits of anticoagulation are prevention of
thrombus extension and recurrence thus reducing the risk of subsequent fatal
pulmonary embolism (PE) [1-5% of recurrent VTE events], post thrombotic
syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTPH). The
main harmful effect of anticoagulation is a major haemorrhage rate of 1-2% per
year [9-13% fatality rate], but highest during initial 3 months of
anticoagulation (when event rate equivalent to ~ 8% per year). It is clear that
not all patients have the same risk of recurrent VTE, nor indeed of major
haemorrhage, therefore no single anticoagulation duration is best for all
patients. Furthermore fixed term anticoagulation >6 months has no long term
benefit as recurrent VTE events will accrue at a similar rate when
anticoagulation is eventually stopped. Therefore the key clinical decision is
between short term and life long anticoagulation. It
can be estimated that a patient with an annual recurrent VTE risk of 5% could
have the same yearly fatality risk of ~0.25% from recurrent VTE (if not
receiving life long anticoagulation) as from fatal haemorrhage (if maintained
on anticoagulation). Ultimately every patient needs to have their risks and
benefits of anticoagulant therapy assessed. However, when the annual risk of
recurrent VTE is clearly less than 5% then only short term anticoagulation can
be justified. If the annual risk of recurrent VTE is in clear excess of 5%
(e.g. ≥8-10%), and the bleeding risk is not above average, then life long
anticoagulation can be justified and should be discussed with the patient. Several
clinical and laboratory markers have been shown to correlate with recurrent VTE
risk and can be used to aid clinical decisions. Markers for lower recurrent VTE
rate include: VTE with reversible provoking factor (e.g surgery, pregnancy,
immobilisation, OCP/ It
remains unclear how these different risk factors interact, although it would
seem that the clinical factors relating to the initial VTE are the strongest
predictors of recurrence risk. The relative importance of risk factors for
bleeding on anticoagulant therapy is less well established, although increasing
age (especially >75y), previous haemorrhage, previous non-cardioembolic
stroke, chronic renal or liver disease and poor anticoagulant control may all
contribute. Ultimately
each patient should have their risks and benefits assessed individually.
However the current evidence base would support the following general advice as
to optimal duration of anticoagulation after 1st VTE: Distal
leg DVT - short term (6–13 weeks) Provoked
PE or proximal DVT - short term (3–6 months), except if major thrombophilia
or active cancer (consider long term) Idiopathic VTE – short term (3-6 months) if >75y
or high bleeding risk Seriously consider life long if PE, and male or
elevated D-dimer
BRIDGING
ANTICOAGULATION FOR INVASIVE PROCEDURES. It
is currently estimated that 1% of the It
is possible to risk-assess patients for both their risk of thrombosis (should
anticoagulation be stopped), and their risk of bleeding (associated with
surgery or a procedure), although currently there are no validated risk
assessment models available. The
majority of patients receive anticoagulant therapy for venous thromboembolic
disease (VTE), atrial fibrillation (AF), or mechanical heart valves (MHV). Those
on anticoagulant therapy for VTE can be risk stratified: those at high risk of
recurrence (VTE within 3 months, antithrombin deficiency), those at moderate
risk of recurrence (VTE >3 months ago, on long term anticoagulation), or low
risk of recurrence (previous VTE now off anticoagulant therapy with no risk
factors for recurrence). In
atrial fibrillation, it is clear that the efficacy of anticoagulation for
stroke prevention is dependent on the INR. The risk of stroke with a
subtherapeutic INR (<2) is more than fivefold greater than with a
therapeutic INR. Patients with AF can be risk stratified to those at high risk of
stroke (CHADS2 score 5-6 or recent stroke or transient ischaemic
attack (TIA)), intermediate risk of stroke (CHADS2 score 3-4), or
low risk of stroke (CHADS2 score 0-1 and no previous stroke or TIA). Similarly
patients with MHV can be risk stratified into those at high risk for
thromboembolism (any mitral valve prostheses, those with ‘older’ aortic
prostheses such as caged-ball or tilting disc), moderate risk (bileaflet aortic
prosthesis with additional risk factors such as AF), or low risk (bileaflet
aortic prostheses with no additional risk factors). Invasive
procedures or surgery vary considerably in their ‘bleeding risk’. Dental
procedures (such as simple dental extractions), dermatological surgery and
endoscopy are low risk procedures for which anticoagulation can usually be
continued (therapeutic INR). High bleeding risk procedures include
neurosurgery, plastic reconstructive surgery and surgery in which a body cavity
is opened. These require cessation of oral anticoagulation, and consideration of
the introduction of a ‘bridging’ anticoagulant. The
recent References: The Perioperative Management of Antithrombotic Therapy. An
Analysis of the Lowest Effective Intensity of Prophylactic Anticoagulation for
Patients with Nonrheumatic Atrial Fibrillation. Hylek E et al. NEJM
335(8):540-546, August 22, 1996 NEW ANTICOAGULANT
DRUGS The need for better anticoagulant drugs has never
been greater. 1-1.5% of the population of Northern Europe, Both in the perioperative period and in individuals
requiring long-term anticoagulation there are significant benefits in providing
an oral anticoagulant which has a predictable dose effect, rapid onset of
action, minimal drug interactions and which does not require monitoring of
anticoagulant effect. Several candidate drugs which will be discussed have
recently been subjected to clinical trials in the prevention of perisurgical
VTE, the management of acute VTE and the prevention of cardioembolic stroke in
patients with atrial fibrillation. UK NEQAS for Blood Coagulation would like to thank the following
commercial concerns for their sponsorship towards the costs of holding the Near
Patient/Point of Care Testing Meeting: CSL Behring UK Limited Elitech
UK Limited Hart
Biologicals Limited/Corgenix UK Limited Pentapharm
GmbH Quadratech
Diagnostics Limited Roche
Diagnostics Limited Sullivan
Cuff Software Limited
S Machin,
Gordon Lowe, Professor of Vascular Medicine,
Rhona Maclean, Sheffield Teaching Hospitals NHS
Foundation
Henry
Watson,
Axis-Shield Diagnostics Limited