Comparison of International Normalized Ratio Measurement between CoaguChek XS Plus and STA-R Coagulation Analyzers

Background. Point-of-care testing (POCT) coagulometers are increasingly being used in the hospital setting. We investigated whether the prothrombin time international normalized ratio (INR) results by CoaguChek XS Plus (Roche Diagnostics GmbH, Mannheim, Germany) can be used reliably without being confirmed with the INR results by STA-R system (Diagnostica Stago S.A.S, Asnières sur Seine, France). Methods. A total of 118 INR measurements by CoaguChek XS Plus and STA-R were compared using Passing/Bablok regression analysis and Bland-Altman plot. Agreement of the INR measurements was further assessed in relation to dosing decision. Results. The correlation of INR measurements between CoaguChek XS Plus and STA-R was excellent (correlation coefficient = 0.964). The mean difference tended to increase as INR results increased and was 0.25 INR in the therapeutic range (2.0-3.0 INR). The overall agreement was fair to good (kappa = 0.679), and 21/118 (17.8%) INR measurements showed a difference in dosing decision. Conclusion. The positive bias of CoaguChek XS Plus may be obvious even in the therapeutic INR range, and dosing decision based on the CoaguChek XS Plus INR results would be different from that based on the STA-R results. The INR measurements by POCT coagulometers still need to be confirmed with the laboratory INR measurements.


Introduction
High-quality anticoagulation management is necessary to keep the narrow therapeutic index medications as effective and safe as possible. Oral anticoagulation therapy should be managed in a systematic and coordinated fashion, incorporating patient education, systematic international normalized ratio (INR) testing, tracking, followup, and good patient communication of results and dosing decisions. Prothrombin time (PT) INR is fundamental to prevent bleeding complications or thrombotic events during oral anticoagulation therapy [1,2]. e target range for INR is dependent on the clinical condition being monitored. For example, targeting an INR of 2.0 to 3.0 for patients with atrial �brillation, deep vein thrombosis, pulmonary embolism, and heart valves on vitamin K antagonist therapy is one of the strong recommendations of the American College of Chest Physicians [3].
Point-of-care testing (POCT) coagulometers are increasingly being used in the general practice setting by primary healthcare providers and by patients and have the potential to improve management of anticoagulation therapy. However, there have been several documented limitations regarding the accuracy and precision of these devices, including greater differences compared with a standard plasma-based methodology as INRs increase above the therapeutic range [4][5][6][7]. Given that INR methods are not harmonized, when monitoring patients on warfarin it is best to keep to one method, and swapping between different laboratory methods or going from laboratory methods to POCT should be discouraged. Nevertheless, using POCT coagulometers is bene�cial in that INR results are readily available using capillary blood from a �ngertip or untreated venous whole blood instead of citrated venous blood for standard laboratory analyzers [8,9]. Accordingly, the need for implementing these POCT coagulometers has increased even in the tertiary care hospitals by the clinicians as well as by the patients.
ere have been limited comparisons between CoaguChek XS Plus (Roche Diagnostics GmbH, Mannheim, Germany) and STA-R automated coagulation system (Diagnostica Stago S.A.S, Asnières sur Seine, France) [10]. In this study, we compared the INR results between CoaguChek XS Plus and STA-R to know how interchangeable both INR results are and whether the CoaguChek XS Plus INR results can be used reliably for following up the patients without being con�rmed or validated with the results of standard laboratory analyzer.

Study Population and INR Measurements.
A total of 118 patients were enrolled in this study. ey were 70 males and 48 females, and their median age was 68 years (range, 5-87 years). During the period between May and July in 2011, they presented to the outpatient clinic of Konkuk University Medical Center, Seoul, Korea, for the baseline screening of their coagulation system or for the routine monitoring of oral anticoagulation therapy. ey were recruited from the departments of cardiovascular surgery ( ), cardiology ( ), neurology ( ), and others ( ). All blood samples were obtained in the blood collection room for outpatients by one certi�ed phlebotomist, who had about 15-year experience for the blood collection and clinical laboratory tests. Each patient was scheduled to draw the venous blood and gave informed consent to participate in this study. Because either capillary blood or venous blood can be used for the analysis in the CoaguChek XS Plus, to avoid dual sampling, venous blood was used for the comparison. is study was approved by the institutional review board.
From a venipuncture approximately 5 mL of blood was drawn into a syringe. e 2.7 mL venous blood was put into a tube containing 3.2% buffered sodium citrate and was sent to the laboratory for the INR measurement using STA-R system. e remaining blood in the syringe was used for the INR measurement by CoaguChek XS Plus without delay.
CoaguChek XS Plus was operated by the same phlebotomist. e preanalytical conditions (differences) were thought to be not in�uential. e CoaguChek XS Plus uses a human recombinant thromboplastin (ISI = 1.01) and employs electrochemical current detection to measure clot formation. In whole blood testing the mean coefficient of variation of the CoaguChek XS Plus PT determination was claimed to be in the range of 1.3% to 1.6% by the manufacturer. e citrated venous blood samples for STA-R were processed and analyzed immediately aer collection according to the routine procedures of the laboratory. e laboratory measurements using STA-Neoplastine CI Plus kit (Diagnostica Stago S.A.S) were considered the reference standard method.

Statistical
Analysis. e INR measurements were analyzed using Pearson's correlation coefficient, Passing/Bablok regression analysis, and Bland-Altman plot. Bland-Altman plot was used to identify mean difference and 95% limits

Results
Based on the STA

Discussion
Although there have been numerous studies on POCT coagulometers, they were all different in the study designs and statistical analyses, leading to diverse conclusions regarding the precision and accuracy of POCT coagulometers [4,6,11,12]. In a recent review, the precision and accuracy of POCT coagulometers were regarded as generally acceptable for clinical use [11]. On the contrary, another systematic review did not provide robust evidence that POCT in general practice improves patient health outcomes and that it has comparable analytical quality to pathology laboratory testing. at review also stated that drawing �rm conclusions are also difficult because of the different measurement technologies used for both POCT and in the laboratory [7].
e CoaguChek XS Plus system was designed for use in the professional setting, differently from the CoaguChek XS system designed for use in patient-self testing [13]. Several studies have evaluated the clinical use of the CoaguChek XS Plus system [10,[13][14][15][16][17]. ose studies were performed in different clinical settings using different laboratory-based tests, and only one of them compared the CoaguChek XS Plus system with the Stago coagulation system (  [10,18]. In addition to the overall correlation and agreement, we further compared the INR results in the lower INR (1.0-2.0 INR) and higher INR (2.0-3.0 INR) ranges and found profound difference or bias even in the therapeutic INR range (Figures 2 and 3).
�hether POCT INR measurement should be con�rmed by the laboratory method or not is still debatable. Some studies insisted that the CoaguChek XS Plus is a reliable tool and dosing decision for vitamin K antagonist therapy may be safely made based on its INR results [13,16]. On the contrary,