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Report 06024 CoaguChek™XS system June 2006
Health and social care working together
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Evaluation of
CoaguChek™ XS system
I Longair, C Gardiner, MA Pescott, IJ Mackie, H Cohen, SJ Machin
Department of Health Evaluation Centre
60 Whitfield Street London W1T 4EU
Tel: 0207 3879300 Ext. 8527 E-mail: [email protected]
© Crown Copyright 2006 Apart from any fair dealing for the purposes of research or private study, or criticism, or review, as permitted under the Copyright, Designs & Patents Act, 1998, this publication may only be reproduced, stored, or transmitted in any form or by any means with the prior permission, in writing, of the Controller of Her Majesty’s Stationery Office (HMSO). Information on reproduction outside these terms can be found on the HMSO website (www.hmso.gov.uk) or e-mail: [email protected].
Contents
Summary ....................................................................................................2
Introduction................................................................................................3 Description of instrument...............................................................................3
Instrument details and operation .............................................................7 Operational details.........................................................................................8
Technical assessment.............................................................................10 Methods .......................................................................................................10 Sample collection.........................................................................................10 Statistical analysis .......................................................................................10 Reference ranges ........................................................................................11 Imprecision ..................................................................................................11 Comparability...............................................................................................13 Effect of haematological parameters ...........................................................20 Carryover .....................................................................................................20 Instrument reliability.....................................................................................21 User assessment .........................................................................................21 Microbiological safety ..................................................................................22 Electrical safety............................................................................................22
Discussion................................................................................................23
Conclusions .............................................................................................25
References ...............................................................................................26
Acknowledgements .................................................................................27
Appendix ..................................................................................................28 Electrical safety certificate ...........................................................................28 Manufacturer’s comments ........................................................................29
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Summary
The CoaguChek XS is a portable, lightweight, point-of-care device which measures Prothrombin time (PT) and International Normalised Ratio (INR) and is intended for use by both healthcare professionals and patients. It measures PT/INR on fresh capillary whole blood applied to disposable test strips. Each strip contains on-board quality control (QC) features to monitor strip integrity.
Operation was found to be simple and no mechanical failures occurred during the evaluation. Three different instruments and three different lots of test strips were assessed for instrument and strip variability and no significant differences found. Low levels of imprecision were recorded for repeat capillary testing in five subjects. Comparability studies in 62 oral antiocoaglant patients showed good agreement with the two reference methods.
Overall, the performance of the CoaguChek XS was found to be satisfactory when compared with reference methods for testing of patients’ samples.
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Introduction
The CoaguChek XS System is a point of care device for measuring prothrombin time (PT) and International Normalised Ratio (INR). It is intended for patient self monitoring and in specific cases for Healthcare professionals, e.g domicilliary visits in the monitoring of oral anticoagulant therapy (OAT). The CoaguChek XS has been CE marked, but has not yet received an independent evaluation in the UK.
The protocol is based on the general protocol for the critical evaluation of coagulometers used for point-of-care testing (PoCT) for the Centre for Evidence-based purchasing (CEP) of the NHS Purchasing and Supply Agency (PASA), Department of Health. For the purpose of these evaluations, PoCT instruments are defined as portable coagulometers designed for use in close proximity to the patient, i.e. at the bedside, in the clinic or by patients themselves. The evaluation uses the reagents, consumables and conditions recommended by the manufacturer of the instrument. Performance is compared to standard laboratory tests on citrated plasma. The definitions of comparability, imprecision, sensitivity, specificity, and carryover will be similar to those previously outlined (Giddings et al., 1989; Gardiner et al., 2006).
Description of instrument
CoaguChek XS meter
The instrument consists of a test strip area and measurement chamber cover, liquid crystal display (LCD) and three buttons (Figure 1). There is a slot for code-chip insertion and an infrared window for data transmission. Underneath is a compartment with removable cover for battery power supply.
The test strip area consists of a guide or rail, which holds the test strip, and a cover that can be removed for cleaning.
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Prior to use one should ensure that the correct chip is inserted in the slot on the monitor and that it matches the code on the test strip container to be used. The buttons on the CoaguChek XS instrument are the on/off button, the (M) button for memory functions and the set button for changing or modifying settings. The CoaguChek XS Plus is currently being developed for Healthcare professionals and is expected for release later this year. This upgraded model is specifically aimed at healthcare workers and will possess additional features to the CoaguChek XS including an external power supply and increased storage and connectivity for data management.
Introduction
Figure 1: Image of the CoaguChek XS Instrument and its components
LCD screen
ON/OFF button
Memory functions button
SET button
Test strip guide
PT INR
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The CoaguChek XS performs an electrochemical measurement of prothrombin time (PT) test using a recombinant human thromboplastin reagent and a peptide substrate, known as Electrocyme TH, which can be used for the determination of serine proteases such as thrombin. Application of sample leads to activation of coagulation by the thromboplastin and results in thrombin generation. Thrombin cleaves Electrocyme TH into a residual peptide and electrochemically active phenylenediamine thereby generating an electrochemical signal. The time elapsed from addition of sample to signal generation is used to calculate the INR value.
Introduction
Principle components The instrument was provided in a portable case containing the CoaguChek XS meter, user manual, CoaguChek Softclix lancing device with instructions for use, CoaguChek Softclix Lancet XL, system carry case and 4 x AAA batteries.
Power supply
The power supply is 4 X 1.5 V (AAA) Alkali-manganese batteries.
Test strip The disposable test strip consists of a sample application area and a test area that contains electrodes and reagents necessary for the PT test, i.e. human recombinant thromboplastin, stabilisers, preservatives and additives as well as on-board control (Figure 2). Blood is applied to the sample application area from where it is drawn into the test area by capillary action and mixed with reagents that cause coagulation to commence. This area contains electrodes for measuring electrochemical changes caused by thrombin cleavage of the peptide substrate. This change in electrical impedance caused by phenylenediamine production is used, in conjunction with calibration information contained within the code chip, to calculate PT and INR.
The test strips do not require refrigeration and are packed in pots of 24 or 48. It is recommended that the pots are re-capped when not in use to avoid excessive humidity, increased temperature and exposure to light, which may damage the strips.
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Introduction
Sample type and volume We initially compared fresh capillary whole blood and venous non-anticoagulated samples for equivalence using the CoaguChek XS. Fresh capillary whole blood was collected from a finger after puncture by a lancet device. At least 10μL of blood was applied to the sample application area either by allowing the sample to drop directly onto the test area or by holding the finger to the side of the sample application area (Figure 2). Non-anticoagulated venous blood was collected into a syringe using 19 or 21 gauge needles with minimal stasis and the sample was then applied immediately by dropping onto the test area.
Figure 2: Application of fingerprick blood sample
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Figure 3: Image of test strip (front view)
Sample application area
Instrument details and operation
Name CoaguChek XS
Manufacturer Roche Diagnostics Ltd. Bell Lane Lewes, East Sussex United Kingdom BN7 1LG
Dimensions Width 78 mm
Depth 138 mm
Height 28 mm
Weight 127 g (without batteries)
Power supply 4 x 1.5V alkali-manganese batteries (type AAA)
Operating environment Temperature 18 - 32 °C
Sample size 10 μL
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Instruction manual The instruction manual was provided in booklet format covering the principles of operation, sample collection, maintenance and troubleshooting.
List price CoaguChek XS £ 399.00
Test strips £ 63.34 (24 test strips)
£ 123.83 (48 test strips)
Instrument details and operation
Operational details
Analytical procedure Prior to testing, the operator should ensure that batteries and the correct code chip are inserted. By pressing the set button the user can modify settings for dates, times, display units, alarm or beep tone and alter settings for INR target ranges. The current date and time should be set and the correct coagulation units selected (i.e., INR) before testing.
The instrument can be placed on a flat surface, or held in the hand and switched on using the button on the front of the monitor. When the instrument is powered on the LCD displays a variety of symbols simultaneously: these have to be checked at each start-up otherwise incorrect readings may be reported (see User Assessment). A flashing symbol indicates that the operator should insert the test strip. A test strip should be removed from its container and inserted into the test strip guide: if inserted correctly a three-digit code becomes legible on the display. This is the chip code for the chip and if this matches the code on the test strip container the memory button (M) on the front of the instrument should be selected to indicate acceptance.
When the displayed chip code does not match the test strip code shown on the container, the strip should be replaced with another with the correct code. Otherwise, a new chip should be inserted to match that of the test strips currently in use.
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When a code is manually accepted the code number ceases flashing on the display and the meter warms to operating temperature accompanied by a flashing hourglass symbol and an audible signal will be heard when ready. A blood drop symbol appears on the display and a 120 second countdown commences on the screen indicating that there are two minutes in which to apply the sample. A fingerstick sample should then be taken and a sample drop of blood applied directly onto the sample application area of the strip (Figures 2 and 3). When sufficient blood is applied, the meter issues an audible alarm and the test commences. An automatic quality control check begins and if this is successful a tick appears alongside the QC symbol. An hourglass symbol flashes until a coagulation result is obtained. Upon successful testing the results appear on the screen. If a QC failure occurs, indicating compromised strip integrity or that insufficient blood was applied, specific error messages will be shown on the display. In this case the operator should start again with a new test strip.
Instrument details and operation
Figure 4: Image of instrument and test strip, showing matching codes on LCD and test strip container
Test strip container
Quality control The CoaguChek XS has several quality control functions including: a check on the different electronic components and instrument functions upon switching on the monitor; test-strip temperature monitoring during testing; checks on test-strip expiry date. Every test strip has an incorporated quality control function which assesses integrity in the measuring channel after sample application. In the measuring channel Resazurin is incorporated and this chemical is sensitive to ambient factors such as light, humidity and temperature and is transformed into Resorufin. The concentration of Resorufin is measured electrochemically and can be considered as a measure of strip damage.
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Similarly, the complete fill of the capillary with blood is detected by current flow between electrodes on the test strip. If the capillary is underfilled an error message (error number 5) will appear on the display.
Operational time and throughput rate The total test time is up to one minute from application of sample. The rate of throughput for the CoaguChek XS was not deemed a relevant investigation since tests will be performed on an individual basis.
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Methods For reference laboratory testing, venous blood was collected into one-tenth volume 0.105M citrate (Vacutainer®, Becton Dickinson, Oxford, UK) using 19 or 21 gauge needles with minimal stasis. Plasma was prepared by centrifugation at 2000g for 10 minutes. The CoaguChek XS PT/INR was compared to two reference methods, using citrated plasma: -
• Innovin (Dade Behring, Marburg, Germany), a recombinant human thromboplastin reagent, on the CA-7000 coagulometer (Sysmex, UK, Ltd)
• PT HS PLUS, a rabbit brain thromboplastin reagent, on the ACL 7000 coagulometer (Instrumentation Laboratory, Warrington, UK)
The International Sensitivity Index (ISI) for Innovin and PT HS Plus were assigned against the international reference preparations, rTF/95, using the WHO thromboplastin calibration programme (WHO Guidelines, 1999). This program uses the recommended procedure of orthogonal regression. The geometric mean prothrombin time (MNPT) was obtained by testing plasma from 20 normal subjects.
Statistical analysis
All references to the mean in subsequent sections allude to the arithmetic mean unless otherwise stated. Data were analysed using Analyse-it TM software (Analyse-It Software, Ltd. PO Box 103, Leeds, UK). The distributions of data were examined for normality by plotting histograms as well as measuring skewness and kurtosis and applying the Kolmogorov-Smirnov goodness-of-fit procedure. For data where the assumption of normality was accepted, one-way analysis of variance (ANOVA) for repeated measurements was employed to test for significant differences between mean values when several groups were compared, a p-value of < 0.05 was taken as staistically significant. When statistically significant differences were observed, paired t-tests were then used to identify specific differences between any two groups.
If data sets were skewed or assumption of normality could not be accepted then non-parametric alternatives were employed, specifically the Friedman ANOVA and Wilcoxon signed-rank test. For the regression analysis, outliers were removed when their standardised residuals were large i.e., where they were found to lie outside the 95 % confidence interval and were not influential points.
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Reference ranges
The International sensitivity index (ISI) for each thromboplastin used in the reference methods was ascertained by testing both healthy subjects (n = 20) and patients on long-term anticoagulant therapy (n = 69) using the 3rd International Standard, rTF/95, by the manual tilt tube technique (Manual) (WHO, 1999) and was found to be 1.04 for Innovin and 1.12 for PT HS Plus. The geometric mean normal prothrombin time (MNPT) was also determined for 20 healthy normal subjects for use in INR calculations (Tables 1 and 2). There were no significant differences in INR between the three reagents in normal subjects.
Table 1: Prothrombin time (s) for normal subjects (n = 20) CoaguChek XS Innovin PT HS Plus
Geometric Mean 12.20 10.29 12.83 Arithmetic Mean 12.21 10.30 12.85 Standard Deviation 0.57 0.31 0.66 Minimum Value 11.30 9.80 11.60 Maximum Value 13.40 10.90 13.90 (± 2SD) 11.07 – 13.35 9.68 – 10.81 11.52 – 14.18 t-test versus CoaguChek XS p < 0.01 p < 0.01 versus Innovin p < 0.01
Table 2: International Normalised Ratio for normal subjects (n = 20) CoaguChek XS Innovin PT HS Plus Geometric Mean 1.02 1.00 1.00 Arithmetic Mean 1.02 1.00 1.00 Standard Deviation 0.06 0.03 0.03 Minimum Value 0.90 0.95 0.95 Maximum Value 1.10 1.06 1.07 (± 2SD) 0.90 – 1.14 0.94 – 1.06 0.93 – 1.07
Imprecision
Within-run imprecision
Within-run imprecision was assessed by testing three replicate capillary blood samples from two normal and three anticoagulant subjects. Overall imprecision was assessed by calculating the mean percentage coefficient of variation as recommended by the Clinical and Laboratory Standards Institute (CLSI EP-15A, 2001). Good imprecision was demonstrated over a range of INR values and these results were satisfactory (Table 3).
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Table 3: Within-run imprecision for the CoaguChek XS Test 1 Test 2 Test 3 Mean INR % CV Sample 1 1.00 1.00 1.00 1.00 0.00 Sample 2 1.00 1.10 1.00 1.03 5.59 Sample 3 2.70 2.70 2.90 2.77 4.17 Sample 4 2.10 2.20 2.10 2.13 2.71 Sample 5 3.20 3.30 3.30 3.27 1.77 Mean 2.00 2.06 2.06 2.04 1.70 N.B. CoaguChek XS INR values are displayed on the device to one decimal place, but for consistency, mean and %CV are shown here and in subsequent tables to two decimal places
Between run imprecision As no stable lyophilised whole blood preparation was available it was not possible to perform between-run imprecision on this instrument.
Instrument variability (capillary versus venous blood) We demonstrated equivalence between non-anticoagulated venous and capillary blood for INR on 15 patients (Table 4). Instrument variability was simultaneously assessed by comparing these INR values from venous non-anticoagulated blood samples obtained from patients receiving OAT on each of three different instruments and using a single test strip lot. Samples were tested concurrently on three instruments using a Latin square design for sampling order to minimise bias (Table 4). No significant differences were found between between venous and capillary samples or between instruments. Table 4: Capillary and venous blood sample INR values on different CoaguChek XS instruments. All samples tested for INR using four strips from the same lot number (n = 15) Instrument (Blood sample)
A (venous)
B (venous)
C (venous)
D (capillary)
Mean 2.89 2.95 2.90 2.89 SD 1.06 1.09 1.07 0.99 Min 1.40 1.40 1.40 1.40 Max 4.90 5.00 4.90 5.00
Test strip variability
This was assessed by simultaneously testing a finger-prick sample on three different lots of test strip. Since earlier studies (Table 4) had shown no significant differences between instruments, individual CoaguChek XS instruments were assigned for each batch of strip. In total 20 samples were obtained which included specimens from patients taking oral anticoagulants. No statistically significant differences were found between the strips when data from all samples were analysed (Table 5).
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Table 5: Between test strip lots variability using venous blood, all (n = 20) Test Strip A B C Mean 2.18 2.19 2.26 SD 0.90 0.90 0.91 Min 0.90 0.90 1.00 Max 3.80 3.90 3.90 ANOVA NS (p = 0.95)
Comparability
INR testing for oral anticoagulant therapy control
In total, sixty-two samples from patients receiving oral anticoagulant therapy were studied, using non-anticoagulated venous blood for the CoaguChek XS and venous anticoagulated plasma samples for the reference methods. The values from the CoaguChek XS compared well with the PT HS Plus reference method and although INR values using Innovin were slightly lower than the other methods no significant differences were identified (Table 6). Good correlation (r ≥ 0.92) was found between the CoaguChek XS and the INR results with both reference methods (Figures 5 - 8). There was no evidence of any bias between the CoaguChek XS method and the PT HS Plus method (Figure 7) although the values from the CoaguChek XS tended to be slightly greater than those from the Innovin method where the mean difference or bias between methods was 0.25, but there was no evidence of increasing scatter with higher average INR values between methods (Figure 7). In the Bland and Altman graph for CoaguChek XS versus PT HS Plus there was increased scatter between methods at higher average INR values (INR ≥ 4.0) (Figure 8). When samples with INR values within therapeutic range by the Innovin method (INR 2.0 – 4.0) were analysed, the findings were broadly similar to those within the whole group (Table 7). When INR results were plotted for the CoagChek XS and the reference methods, the regression line for OAT patients passed through or close to the data points from normal subjects, suggesting that the reagent systems were not significantly miscalibrated in terms of the ISI value (Figures 9 and 10). Table 6: INR values for all oral anticoagulant samples (n = 62)
CoaguChek XS Innovin PT HS Plus Arithmetic Mean 2.81 2.57 2.94 Standard Deviation 0.94 0.87 0.82 Minimum Value 1.20 1.21 1.37 Maximum Value 5.00 4.84 4.82 (± 2SD) 0.93 - 4.69 0.84 - 4.30 1.31 - 4.57 ANOVA NS (p = 0.06)
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Table 7: INR values for oral anticoagulant samples within therapeutic range (n = 46)
CoaguChek XS Innovin PT HS Plus Arithmetic Mean 2.89 2.61 3.03 Standard Deviation 0.69 0.60 0.47 Minimum Value 1.70 1.45 2.06 Maximum Value 4.70 4.08 3.95 (± 2SD) 1.50 - 4.26 1.40 - 3.82 2.08 - 3.97 ANOVA p < 0.01 T-test versus CoaguChek XS p < 0.01 p = 0.01 versus Innovin p < 0.01
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Figure 5: INR for all oral anticoagulant patients. CoaguChek XS v Innovin
Figure 6: INR for all oral anticoagulant patients. CoaguChek XS v Innovin: Bland and Altman diagram
0 1 2 3 4 5 6
Mean INR
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
INR
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Mean0.25
- 2 SD- 0.20
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Figure 7: INR for all oral anticoagulant patients. CoaguChek XS v PT HS Plus
0 1 2 3 4 5 6
PT HS Plus (INR)
0
1
2
3
4
5
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NR
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y = 1.07x - 0.33r = 0.92
Figure 8: INR for all oral anticoagulant patients. CoaguChek XS v PT HS Plus: Bland and Altman diagram
0 1 2 3 4 5 6
Mean INR
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
INR
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Plus
+ 2SD 0.60
Mean- 0.13
- 2SD- 0.86
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Figure 9: INR values for OAC patients in the therapeutic range and normal subjects on the CoaguChek XS v Innovin (regression line calculated from patient data only)
0 1 2 3 4 5 6
Innovin (INR)
0
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5
6
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OAC samples Normals
y = 1.10x + 0.05r = 0.92
Figure 10: INR values for OAC patients in the therapeutic range and normal subjects on the CoaguChek XS v PT HS Plus (regression line calculated from patient data only)
0 1 2 3 4 5 6
PT HS Plus (INR)
0
1
2
3
4
5
6
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OAC samples Normals
y =0.97x - 0.20r = 0.76
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Stratified INR data Stratification of INR results with respect to the values obtained by the PT HS Plus method showed some small but statistically significant differences between the CoaguChek XS and Innovin methods at all levels of stratification (Table 8). It is apparent, however, that the Innovin INR values were consistently lower than for both CoaguChek XS and PT HS Plus methods, except at higher INR values and although statistically significant, the differences are small and not likely to be of clinical significance. There was broad agreement between CoaguChek XS and PT HS Plus INR values at all levels of stratification except in the range of about 2.0 – 3.0 INR units. At these ranges the CoaguChek XS INR values were slightly lower than the reference method and approached statistical significance. The differences between the methods were minor and, again, unlikely to be of clinical significance.
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Table 8: INR subgroups for OAT samples (n = 62) CoaguChek XS Innovin PT HS Plus
INR 1.00 – 1.99 (n = 10) Mean 1.56 1.45 1.66 SD 0.23 0.21 0.19 Min 1.20 1.21 1.37 Max 1.90 1.83 1.83 t-test v CoaguChek XS p < 0.01 NS v Innovin p < 0.01
INR 2.00 – 2.49 (n = 7) Mean 2.01 1.83 2.30 SD 0.32 0.16 0.15 Min 1.80 1.63 2.06 Max 2.70 2.13 2.45 t-test v CoaguChek XS p = 0.04 p = 0.05 v Innovin p < 0.01
INR 2.50 – 2.99 (n = 13) Mean 2.51 2.29 2.76 SD 0.41 0.34 0.17 Min 1.70 1.45 2.53 Max 3.10 2.73 2.98 t-test v CoaguChek XS p < 0.01 p = 0.02 v Innovin p < 0.01
INR 3.00 – 3.49 (n = 18) Mean 3.07 2.75 3.20 SD 0.31 0.21 0.15 Min 2.60 2.37 3.01 Max 3.80 3.18 3.47 t-test v CoaguChek XS p < 0.01 p = 0.04 v Innovin p < 0.01
INR 3.50 – 3.99 (n = 8) Mean 3.85 3.53 3.73 SD 0.54 0.42 0.16 Min 2.90 2.87 3.56 Max 4.70 4.08 3.95 t-test v CoaguChek XS p = 0.04 NS v Innovin NS
INR > 3.99 (n = 6 ) Mean 4.32 4.06 4.40 SD 0.71 0.77 0.28 Min 3.10 2.71 4.01 Max 5.00 4.84 4.82 t-test v CoaguChek XS NS NS v Innovin NS
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Effect of haematological parameters on CoaguChek XS
We assessed the effects of elevated white blood cell count (WBC ≥ 10 x 109/L) and increased haematocrit (Hct ≥ 0.450) on the CoaguChek XS and compared INR values with those obtained by the reference methods. No statistically significant differences were found between INR by CoaguChek XS and the reference methods for samples with leucocytosis (Table 9). However it should be noted that only five suitable samples were identified and any statistical inference should be exercised with caution for such a small sample size. Results from 24 samples with elevated haematocrit values (Hct ≥ 0.45) showed significantly different INR values between methods (ANOVA p < 0.01, Table 10). However the differences were restricted to the Innovin method, which had lower mean INR values than either the CoaguChek XS or PT-HS Plus methods. The Innovin method has consistently given lower INR values throughout the evaluation. There was no detectable trend towards higher or lower INR values (compared to either reference method), with increasing haematocrit. Table 9: INR values for samples with leucocytosis (WBC > 10x109/ L, n = 5)
SUBJECT WBC ( x109/L)
CoaguChek XS
Innovin PT HS Plus
Normal A 10.10 1.00 0.96 0.93 OAC A 12.81 2.70 2.37 3.08 OAC B 10.31 2.50 2.29 2.93 OAC C 10.72 4.60 3.96 4.01 OAC D 11.61 3.00 2.86 3.08 Median 10.72 2.70 2.37 3.08 IQR 1.30 0.50 0.57 0.16 Friedman ANOVA NS
Table 10: INR values for samples with Haematocrit ≥ 0.450 (n = 24) HCT CoaguChek
XS Innovin PT HS Plus
Mean 0.478 2.58 2.38 2.68 SD 0.027 1.26 1.10 1.17 Min 0.452 0.90 0.97 0.95 Max 0.544 4.70 4.08 4.41 ANOVA (between methods) p < 0.01 t-test v CoaguChek XS p < 0.01 NS v Innovin p < 0.01
Carryover The test strips are designed for single use only. Therefore, no carryover can occur.
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Instrument reliability No mechanical failures were encountered during the evaluation. Only two error messages from 167 tests occurred post-testing i.e. after the code numbers on the instrument and test-strips were confirmed as matching: one error pertained to blood application (Error 5) and the other was a measurement error (Error 6). No quality control errors occurred..
User assessment
As with most point-of-care monitors, the CoaguChek XS only displays the INR results to one place of decimals, whereas typical laboratory generated INR values are recorded to two decimal places. At present, there is no quantitative quality control material available for the CoaguChek XS. Furthermore, as only fresh whole blood can be used, it is not possible to test external quality assurance materials. It is recommended that some form of external quality control as well as external quality assurance are regularly performed on all point-of-care coagulation monitors (England et al, 1995; Fitzmaurice et al 2005). Consequently, independent quality assurance of the CoaguChek XS would need to be performed by periodically testing a paired capillary blood sample on a separate CoaguChek XS (or other point-of-care monitor) maintained by the practitioner managing the oral anticoagulant care, or using a paired venous sample tested by a laboratory based coagulometer.
Each code chip provides the instrument with lot specific calibration data and expiry date. It was observed that a mismatch between the test strip code and the chip code was possible. If the user places a test strip from a different lot on the monitor, but then presses the memory button rather than replacing with tests strips matching that of the current chip an incorrect INR value may result. The manufacturer’s manual does emphasise the importance of matching test strips to the current code chips but we feel that this should be further highlighted in any protocol devised for self-testing with this instrument. Obviously a ‘fail-safe’ electronic check would be preferable. Each time the monitor is switched on a full display check appears showing all symbols that may be displayed. There is a facility to call up the display after start-up to allow checking against figures in the user manual. The manufacturer suggests that this should be checked frequently to ensure that reading errors do not occur. We felt that the light weight compact size of the instrument were advantageous when testing on patients: easily portable to where the patient was being finger-pricked and thus testing could readily be performed in a timely manner with minimal likelihood of blood spillages. We also noted the low rate of test-strip failure, minimising the cost of repeat testing.
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Technical assessment
Microbiological safety The CoaguChek XS test-strips are single-use and disposable and since the device has no accessible moving parts, microbiological safety could not be assessed in the usual manner. The lancet devices used throughout the evaluation have safety features making it impossible to re-use lancets. The manufacturer recommended that any contamination of the CoaguChek XS external surfaces should be removed using commercially available lint-free swabs and normal alcohol-free domestic cleaning agents and dried using soft lint-free cloths. Similarly the test strip guide area can be cleaned by lifting the measurement chamber flap and cleaning with a moistened swab or cotton bud. Electrical safety The manufacturer supplied a certificate of conformity to EN 61010 –1 and this is shown in the appendix.
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Discussion
The CoaguChek XS is a small, portable device intended primarily for use by patients and non-laboratory based medical staff to generate INR values for oral anticoagulant management. The CoaguChek XS device measures PT/INR on capillary whole blood and non-anticoagulated venous blood but not citrated blood. The test-strips are composed of three conjoined plastic strips creating a sample application area, a blood flow area, and a test area with electrodes. All reagents necessary for the test and internal QC are contained within the designated coagulation chemistry test area. Operation was found to be simple and no mechanical failures specific to the device were encountered during the evaluation. There were very few test-strip failures encountered during the evaluation: only two test failures occurred in 167 tests performed on both capillary and venous samples. The application of blood to the sample area was easy and convenient. The machine was portable, allowing the operator to hold the instrument during testing, rather than having to be placed on a flat and stable surface. These factors probably contributed to the low test strip wastage rate.
No significant differences were observed between three instruments in simultaneous testing of 20 blood samples. Similarly, between-lot variability was found to be low with no significant differences found between different batches of test strips. Testing two normal and three OAT patients’ samples assessed within-run imprecision with the same strip lots giving acceptable levels of imprecision.
Reference ranges for twenty normal healthy subjects were obtained for the CoaguChek XS and the reference methods. For PT, statistically significant differences were found between various methods although this was not unexpected due to the differing sensitivity of the reagents. When the values were converted to INR these statistically significant differences disappeared.
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Plasma samples from 62 patients receiving oral anticoagulation were tested using the CoaguChek XS and the results compared with those from two reference methods. Good correlation was obtained between the CoaguChek XS and both reference methods. However, increased scatter was observed at higher mean INR values (INR ≥ 4), between CoaguChek XS and the PT HS Plus reference method. The Innovin reference method gave consistently lower INR values than the CoaguChek XS and PT HS Plus for all stratified values, (except those >4.0), but although these differences were statistically significant they were small in magnitude and not clinically significant. Furthermore, if an ISI value of 0.99 for rTF/95 were used, as suggested by Poller et al (2005), these differences were attenuated
Analysis of data for CoaguChek XS values showed that 54/60 (90.0%) of results were within 0.5 INR units when compared with Innovin and 60/60 (100%) were within 1.0 INR units. Similarly 49/56 (87.5%) and 55/56 (98.2%) of results were within 0.5 INR units and 1.0 INR units respectively, when CoaguChek XS
Discussion
values were compared with PT-HS Plus. If the average INR was greater than 4.0 units the results were excluded from this analysis.
The regression plots comparing the CoaguChek XS with the two different reference methods showed few discrepancies with the Innovin or PT HS Plus methods. The minor differences that were found were generally at the high end of the INR range and mostly where INR ≥ 4.0 units where the INR system is known to be unreliable. Similarly when we plotted CoaguChek XS values within the therapeutic range few discrepancies were identified against the PT HS Plus method and again these occurred only at high INR values.
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Conclusions
This study showed that the CoaguChek XS instrument and test strips gave accurate and reproducible INR results when compared with two reference methods for PT and INR. The instrument was found to be easy to use with no system failures and very few test strip failures occurring during the evaluation. This indicates that the CoaguChek XS is a suitable system for near-patient testing in the monitoring of oral anticoagulant therapy for most patients.
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References
CLSI E15-A. User demonstration of performance for precision and accuracy; Approved guideline (2001) Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne, PA 19087-1898 USA
England JM, Hyde K, Lewis SM, Mackie IJ, Rowan RM. Guidelines for near-patient testing: haematology. Clin Lab Haem 1995; 17: 300-309
Fitzmaurice DA, Gardiner C, Kitchen S, Mackie I, Murray ET, Machin SJ. An evidence-based review and guidelines for patient self-testing and management of oral anticoagulation. Br J Haematol. 2005;131:156-65.
Gardiner C, Kitchen S, Dauer RJ, Kottke-Marchant K, Adcock DM. Recommendations for Evaluation of Coagulation Analyzers. Laboratory Hematology 2006; 12(1): 32-38.
Giddings JC, Hall P, Basterfield P, Kennedy DA, George AJ, Hall R, Lamont J, Stirling Y. Protocol for the evaluation of automated blood coagulation instruments (coagulometers) for determination of the international normalised ratio. Med Lab Sciences 1989; 46: 39-44
Poller L, Keown M, Chauhan N, van den Besselaar AM, Tripodi A, Shiach C, Jespersen J. European Concerted Action on Anticoagulation. A multicentre calibration study of WHO international reference preparations for thromboplastin, rabbit (RBT/90) and human (rTF/95). J Clin Pathol 2005; 58: 667-9 WHO Expert Committee on Biological Standardisation (1999) Requirements for thromboplastins and plasma used to control anticoagulant therapy. WHO Technical Report Series. Report 889. 64-93
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Acknowledgements
We wish to thank Hilary Erwin and phlebotomy staff as well as the patients at University College Hospital for their help during this evaluation.
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Appendix
Electrical safety certificate
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Manufacturer’s comments
