International Journal of Laboratory Hematology The Official journal of the International Society for Laboratory Hematology
ORIGINAL ARTICLE
INTERNAT IONAL JOURNAL OF LABORATO RY HEMATO LOGY
Establishing an external quality assessment scheme for pointof-care international normalized ratio in Thailand P. TIENTADAKUL, A. CHUNTARUT
Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Correspondence: Dr Panutsaya Tientadakul, Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Prannok Rd, Bangkoknoi, Bangkok 10700, Thailand. Tel.: (662) 418 6587; Fax: (662) 418 1367; E-mail: panutsaya.tie@mahidol. ac.th
Portions of this study were presented at the International Society for Laboratory Hematology (ISLH) in The Hague, the Netherlands, on May 15–17, 2014. doi:10.1111/ijlh.12321
Received 26 September 2014; accepted for publication 20 November 2014
S U M M A RY Introduction: Effective warfarin therapy management has gained national interest, resulting in the increased use of point-of-care testing (POCT) for international normalized ratio (INR). External quality assessment (EQA) is recommended to ensure quality of the testing. CoaguChek XS and CoaguChek XS Plus are the only commonly available POCT INR monitors in Thailand. Therefore, Thailand NEQAS for Blood Coagulation initiated the scheme for POCT INR in 2013, including only hospitals using these devices. Methods: Questionnaires were sent to the hospitals, enquiring about their interest in EQA participation. Two surveys were distributed; each included five certified European Concerted Action on Anticoagulation (ECAA) INR plasma sets. Unsatisfactory performance was indicated by a 15% deviation from the certified mean INR value. Results: There were 156 hospitals using the devices. Thirty-five hospitals responded to the questionnaires. Medical personnel undertaking POCT INR were limited to laboratory staff in 29 (83%) of these centers, and 31 hospitals actually participated. The medians of results from participants were the same or nearly the same as the certified mean INRs. Conclusion: External quality assessment for POCT INR in Thailand is feasible using the ECAA plasmas as control materials. The results therefore appear encouraging to other developing countries to establish their own EQA schemes.
Keywords Point-of care testing, international normalized ratio, external quality assessment, proficiency testing, blood coagulation
INTRODUCTION Warfarin is a vitamin K antagonist, which has been used for prevention of venous and arterial thrombosis for many decades. The quality of monitoring and © 2014 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 509–514
dosage management, which aim to keep the intensity of the anticoagulant within the therapeutic range, has a strong relationship with adverse events, whether bleeding or thromboembolism [1]. Use of a point-ofcare testing (POCT) device for international normalized 509
510
P. TIENTADAKUL AND A. CHUNTARUT | EQA FOR POCT INR IN THAILAND
ratio (INR) monitoring in anticoagulant clinics and patient self-testing has shown to improve outcomes [2]. In Thailand, effective warfarin therapy management has gained national interest. [3, 4] One of the limitations hindering this policy is the availability of laboratory testing for INR [4]. As a result, POCT INR has been increasingly introduced to facilitate the management. External quality assessment (EQA) for POCT INR has been demonstrated to be beneficial to the quality of test [5], and it is recommended that healthcare providers using POCT INR devices to participate in an independent EQA program [6]. Notwithstanding the several guidelines, many countries still have no EQA scheme for POCT INR. For example, in 2012, at least nineteen countries did not provide this EQA service [7]. One of difficult obstacles mentioned in that report is the use of lyophilized plasma as EQA material, which may differ from the native whole blood sample for POCT INR. The matrix effects make it not possible for comparison between different brands of instruments [7]. In Thailand, CoaguChek XS and CoaguChek XS Plus (Roche Diagnostics, Mannheim, Germany), are the only commonly available POC-INR monitors, and the latter has additional feature of connectivity to computer and data management. Control material produced by European Concerted Action on Anticoagulation (ECAA) which is suitable for these devices are available [8]. Therefore, it would be feasible for Thailand National External Quality Assessment Scheme (NEQAS) for Blood Coagulation to initiate an EQA for POCT INR. We describe here how we established the program, its results, problems and solutions.
M AT E R I A L S A N D M E T H O D S
scheme, whether a pipette was needed for sample reconstitution, and whether there was a conflict of interest with the company. EQA materials A single batch of the European Concerted Action on Anticoagulation (ECAA) INR plasma set comprising 5 lyophilized artificially depleted plasmas was used as EQA materials. The ranges of INR values of these plasmas were certified by three certifying centers in Europe with the methods described elsewhere [8]. Reagent grade water and calcium chloride were included in the set of EQA samples. Test procedure Each vial of EQA sample was reconstituted with 0.5 mL of the water and allowed to stand for 10 min at room temperature, but no longer than 30 min. After gently mixing the plasma, the POC device was prepared for the performance of testing, and then, 0.5 mL of calcium chloride was added to the vial containing plasma and mixed well. The recalcified plasma was applied to the test strip within 15 s. This procedure was repeated for all five samples. More than one device could be tested simultaneously within this limited time. Performance evaluation The certified acceptable range for each sample within 15% deviation of mean INR was used for evaluation of participants’ results. Median INR of these results was also calculated after excluding outliers, to find out whether it would differ from the certified mean. Although the certified INR values in the leaflet were assigned for CoaguChek XS, we also used them to evaluate the results of CoaguChek XS Plus.
Recruitment of participants In September 2012, we asked Roche Diagnostics, Thailand, to distribute questionnaires to its healthcare professional users of CoaguChek XS and XS Plus monitors enquiring about their interest in participation of an EQA program and the practice of POCT INR testing in their hospitals, that is, type of instrument, personnel who perform testing, and number of tests per week. We also informed them about the details of
Operation of the EQA scheme Samples were distributed by registered post twice a year, together with instructions and reply forms. Necessary information in the form included details of the responsible person, date of receipt and specimen analysis, type of instrument: CoaguChek XS or CoaguChek XS Plus, INR results of five plasmas, strip lot, and reports of unexpected events during the testing of © 2014 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 509–514
P. TIENTADAKUL AND A. CHUNTARUT | EQA FOR POCT INR IN THAILAND
each sample. The latter was recorded to help interpret the result out of acceptable range. Results could be returned by post, facsimile, or email. After the closing date, which was 15–17 days after distribution, the results were analyzed and reported back by post. Turnaround time of the scheme was about 1 month. Statistical analysis
R E S U LT S Data from the questionnaires Thirty-five questionnaires were returned. The exact number distributed by the company was not known. However, the total number of hospitals using CoaguChek XS and/or CoaguChek XS Plus was around 156. Types of instruments and healthcare professionals who performed test are shown in Figures 1 and 2, respectively. Approximate test requests/week ranged from 2 to 80 (median 11), from the 26 hospitals that answered this question. Results of two surveys in 2013 The participants totaled 31 hospitals. The response rate of the first survey was 97% (30 of 31) because one hospital had lost its results. That of second survey
5 (14%)
12 (34%)
1 (3%)
1 (3%)
Laboratory staff
Laboratory staff & nurse Laboratory staff & nurse & pharmacist
29 (83%)
Nurse
Nurse & doctor No answer
Median of INR results and coefficient of variation (CV) were calculated using Microsoft Excel 2007 (Microsoft Corporation, Redmond, WA, USA). Outlier was defined as more than 3 standard deviation (SD) from median [9].
2 (6%)
1 (3%)
1 2 (3%) (5%)
511
CoaguCheck XS
16 (46%)
CoaguCheck XS plus Both No answer
Figure 1. Type of point-of-care INR monitors responded from 35 hospitals.
© 2014 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 509–514
Figure 2. Healthcare professionals performing pointof-care INR testing. (N = 35 hospitals).
was 94% (29 of 31). There were at least nine and six lot numbers of test strips in the first and second survey, respectively. The results of both surveys are displayed in Table 1. In the first survey, there was one hospital performed the EQA testing on three monitors using one set of plasmas, so that the total results used for calculation were 32 instead of 30, which was the number of responders. One result (INR 2.2) was outside the acceptable range of sample No. 2 (INR 2.3–3.1). Another unacceptable result (INR 3.3) was from another hospital. In the second survey, only one result of sample No. 5 was outside the acceptable range, INR 3.3, which was considered as an outlier. This hospital and those with unacceptable results in the previous survey were not the same. The certified mean INRs and medians were equal for three samples, and the difference of the other two samples ranged from 0.1 to 0.3 INR unit. The overall average CV was 3.3% (with one outliers removed). When comparing the results of both surveys in individual hospitals, most hospitals had differences in each sample
ORIGINAL ARTICLE
INTERNAT IONAL JOURNAL OF LABORATO RY HEMATO LOGY
Establishing an external quality assessment scheme for pointof-care international normalized ratio in Thailand P. TIENTADAKUL, A. CHUNTARUT
Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Correspondence: Dr Panutsaya Tientadakul, Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Prannok Rd, Bangkoknoi, Bangkok 10700, Thailand. Tel.: (662) 418 6587; Fax: (662) 418 1367; E-mail: panutsaya.tie@mahidol. ac.th
Portions of this study were presented at the International Society for Laboratory Hematology (ISLH) in The Hague, the Netherlands, on May 15–17, 2014. doi:10.1111/ijlh.12321
Received 26 September 2014; accepted for publication 20 November 2014
S U M M A RY Introduction: Effective warfarin therapy management has gained national interest, resulting in the increased use of point-of-care testing (POCT) for international normalized ratio (INR). External quality assessment (EQA) is recommended to ensure quality of the testing. CoaguChek XS and CoaguChek XS Plus are the only commonly available POCT INR monitors in Thailand. Therefore, Thailand NEQAS for Blood Coagulation initiated the scheme for POCT INR in 2013, including only hospitals using these devices. Methods: Questionnaires were sent to the hospitals, enquiring about their interest in EQA participation. Two surveys were distributed; each included five certified European Concerted Action on Anticoagulation (ECAA) INR plasma sets. Unsatisfactory performance was indicated by a 15% deviation from the certified mean INR value. Results: There were 156 hospitals using the devices. Thirty-five hospitals responded to the questionnaires. Medical personnel undertaking POCT INR were limited to laboratory staff in 29 (83%) of these centers, and 31 hospitals actually participated. The medians of results from participants were the same or nearly the same as the certified mean INRs. Conclusion: External quality assessment for POCT INR in Thailand is feasible using the ECAA plasmas as control materials. The results therefore appear encouraging to other developing countries to establish their own EQA schemes.
Keywords Point-of care testing, international normalized ratio, external quality assessment, proficiency testing, blood coagulation
INTRODUCTION Warfarin is a vitamin K antagonist, which has been used for prevention of venous and arterial thrombosis for many decades. The quality of monitoring and © 2014 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 509–514
dosage management, which aim to keep the intensity of the anticoagulant within the therapeutic range, has a strong relationship with adverse events, whether bleeding or thromboembolism [1]. Use of a point-ofcare testing (POCT) device for international normalized 509
510
P. TIENTADAKUL AND A. CHUNTARUT | EQA FOR POCT INR IN THAILAND
ratio (INR) monitoring in anticoagulant clinics and patient self-testing has shown to improve outcomes [2]. In Thailand, effective warfarin therapy management has gained national interest. [3, 4] One of the limitations hindering this policy is the availability of laboratory testing for INR [4]. As a result, POCT INR has been increasingly introduced to facilitate the management. External quality assessment (EQA) for POCT INR has been demonstrated to be beneficial to the quality of test [5], and it is recommended that healthcare providers using POCT INR devices to participate in an independent EQA program [6]. Notwithstanding the several guidelines, many countries still have no EQA scheme for POCT INR. For example, in 2012, at least nineteen countries did not provide this EQA service [7]. One of difficult obstacles mentioned in that report is the use of lyophilized plasma as EQA material, which may differ from the native whole blood sample for POCT INR. The matrix effects make it not possible for comparison between different brands of instruments [7]. In Thailand, CoaguChek XS and CoaguChek XS Plus (Roche Diagnostics, Mannheim, Germany), are the only commonly available POC-INR monitors, and the latter has additional feature of connectivity to computer and data management. Control material produced by European Concerted Action on Anticoagulation (ECAA) which is suitable for these devices are available [8]. Therefore, it would be feasible for Thailand National External Quality Assessment Scheme (NEQAS) for Blood Coagulation to initiate an EQA for POCT INR. We describe here how we established the program, its results, problems and solutions.
M AT E R I A L S A N D M E T H O D S
scheme, whether a pipette was needed for sample reconstitution, and whether there was a conflict of interest with the company. EQA materials A single batch of the European Concerted Action on Anticoagulation (ECAA) INR plasma set comprising 5 lyophilized artificially depleted plasmas was used as EQA materials. The ranges of INR values of these plasmas were certified by three certifying centers in Europe with the methods described elsewhere [8]. Reagent grade water and calcium chloride were included in the set of EQA samples. Test procedure Each vial of EQA sample was reconstituted with 0.5 mL of the water and allowed to stand for 10 min at room temperature, but no longer than 30 min. After gently mixing the plasma, the POC device was prepared for the performance of testing, and then, 0.5 mL of calcium chloride was added to the vial containing plasma and mixed well. The recalcified plasma was applied to the test strip within 15 s. This procedure was repeated for all five samples. More than one device could be tested simultaneously within this limited time. Performance evaluation The certified acceptable range for each sample within 15% deviation of mean INR was used for evaluation of participants’ results. Median INR of these results was also calculated after excluding outliers, to find out whether it would differ from the certified mean. Although the certified INR values in the leaflet were assigned for CoaguChek XS, we also used them to evaluate the results of CoaguChek XS Plus.
Recruitment of participants In September 2012, we asked Roche Diagnostics, Thailand, to distribute questionnaires to its healthcare professional users of CoaguChek XS and XS Plus monitors enquiring about their interest in participation of an EQA program and the practice of POCT INR testing in their hospitals, that is, type of instrument, personnel who perform testing, and number of tests per week. We also informed them about the details of
Operation of the EQA scheme Samples were distributed by registered post twice a year, together with instructions and reply forms. Necessary information in the form included details of the responsible person, date of receipt and specimen analysis, type of instrument: CoaguChek XS or CoaguChek XS Plus, INR results of five plasmas, strip lot, and reports of unexpected events during the testing of © 2014 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 509–514
P. TIENTADAKUL AND A. CHUNTARUT | EQA FOR POCT INR IN THAILAND
each sample. The latter was recorded to help interpret the result out of acceptable range. Results could be returned by post, facsimile, or email. After the closing date, which was 15–17 days after distribution, the results were analyzed and reported back by post. Turnaround time of the scheme was about 1 month. Statistical analysis
R E S U LT S Data from the questionnaires Thirty-five questionnaires were returned. The exact number distributed by the company was not known. However, the total number of hospitals using CoaguChek XS and/or CoaguChek XS Plus was around 156. Types of instruments and healthcare professionals who performed test are shown in Figures 1 and 2, respectively. Approximate test requests/week ranged from 2 to 80 (median 11), from the 26 hospitals that answered this question. Results of two surveys in 2013 The participants totaled 31 hospitals. The response rate of the first survey was 97% (30 of 31) because one hospital had lost its results. That of second survey
5 (14%)
12 (34%)
1 (3%)
1 (3%)
Laboratory staff
Laboratory staff & nurse Laboratory staff & nurse & pharmacist
29 (83%)
Nurse
Nurse & doctor No answer
Median of INR results and coefficient of variation (CV) were calculated using Microsoft Excel 2007 (Microsoft Corporation, Redmond, WA, USA). Outlier was defined as more than 3 standard deviation (SD) from median [9].
2 (6%)
1 (3%)
1 2 (3%) (5%)
511
CoaguCheck XS
16 (46%)
CoaguCheck XS plus Both No answer
Figure 1. Type of point-of-care INR monitors responded from 35 hospitals.
© 2014 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 509–514
Figure 2. Healthcare professionals performing pointof-care INR testing. (N = 35 hospitals).
was 94% (29 of 31). There were at least nine and six lot numbers of test strips in the first and second survey, respectively. The results of both surveys are displayed in Table 1. In the first survey, there was one hospital performed the EQA testing on three monitors using one set of plasmas, so that the total results used for calculation were 32 instead of 30, which was the number of responders. One result (INR 2.2) was outside the acceptable range of sample No. 2 (INR 2.3–3.1). Another unacceptable result (INR 3.3) was from another hospital. In the second survey, only one result of sample No. 5 was outside the acceptable range, INR 3.3, which was considered as an outlier. This hospital and those with unacceptable results in the previous survey were not the same. The certified mean INRs and medians were equal for three samples, and the difference of the other two samples ranged from 0.1 to 0.3 INR unit. The overall average CV was 3.3% (with one outliers removed). When comparing the results of both surveys in individual hospitals, most hospitals had differences in each sample
