Ann Lab Med.  2023 Jul;43(4):337-344. 10.3343/alm.2023.43.4.337.

Comparison of the International Normalized Ratio Between a Point-of-Care Test and a Conventional Laboratory Test: the Latter Performs Better in Assessing Warfarin-induced Changes in Coagulation Factors

• Kim YS
• Choi JW
• Song SH
• Hwang HY
• Sohn SH
• Kim JS
• Kang Y
• Gu JY
• Kim KH
• Kim HK

• KMID: 2551951
• DOI: http://doi.org/10.3343/alm.2023.43.4.337

Abstract

Background
Point-of-care testing (POCT) coagulometers are increasingly used for monitoring warfarin therapy. However, in high international normalized ratio (INR) ranges, significant discrepancy in the INR between POCT and conventional laboratory tests occurs. We compared the INR of POCT (CoaguChek XS Plus; Roche Diagnostics, Mannheim, Germany) with that of a conventional laboratory test (ACL TOP 750; Instrumentation Laboratory SpA, Milan, Italy) and explored possible reasons for discrepancy.
Methods
Paired POCT and conventional laboratory test INRs were analyzed in 400 samples from 126 patients undergoing warfarin therapy after cardiac surgery. Coagulation factor and thrombin generation tests were compared using the Mann–Whitney U test. Correlations between coagulation factors and INRs were determined using Pearson correlation coefficients.
Results
The mean difference in the INR between the tests increased at high INR ranges. Endogenous thrombin potential levels were decreased at INR <2.0 for CoaguChek XS Plus and 2.0< INR <3.0 for ACL TOP 750 compared with those at INR <2.0 for both tests, indicating a better performance of ACL TOP 750 in assessing thrombin changes. The correlation coefficients of coagulation factors were stronger for ACL TOP 750 INR than for CoaguChek XS Plus INR. Vitamin K-dependent coagulation factors were found to contribute to the INR discrepancy.
Conclusions
Decreases in vitamin K-dependent coagulation and anticoagulation factors can explain the significant discrepancy between the two tests in high INR ranges. Since conventional laboratory test INR values are more reliable than POCT INR values, a confirmatory conventional laboratory test is required for high INR ranges.

Keyword

International normalized ratio; Point-of-care testing; Warfarin; Blood coagulation factors; Comparative study; Cardiac surgery

Figure

• 

  Fig. 1 Comparison of CoaguChek XS Plus and ACL TOP 750 INR values using Passing–Bablok regression analysis. Solid lines, regression lines; dashed lines, 95% CI limits. Passing–Bablok regression analysis was performed for (A) the total range of INR values (N=400), (B) INR values ≤3.0 (N=320), and (C) INR values >3.0 (N=80). (D–F) Comparison of CoaguChek XS Plus and ACL TOP 750 INR values using Bland–Altman plots (D) in the total range of mean INR values, (E) at INR values ≤3, and (F) at INR values >3.0. The difference between two values (Y-axis) is plotted against the average of ACL TOP 750 and CoaguChek XS Plus values (X-axis). Solid lines, mean differences in INR values between the two tests; dashed lines, lower and upper limits of agreement (mean±1.96 SD) between test results. Abbreviations: INR, international normalized ratio; CI, confidence interval.

• 

  Fig. 2 Differences in (A) ETP, (B) peak thrombin, (C) lag time, and (D) time to peak between the accord group (INR <2.0 both by CoaguChek XS Plus and ACL TOP 750) and discrepancy group 1 (2.0≤ INR ≤3.0 by ACL TOP 750 and INR <2.0 by CoaguChek XS Plus). The red symbol in Fig. 2D indicates a value higher than the upper outer fence, which is calculated by adding three times the interquartile range to the 3rd quartile. Abbreviations: ETP, endogenous thrombin potential; INR, international normalized ratio.

• 

  Fig. 3 Comparison of (A) factor II, (B) factor VII, (C) factor IX, (D) factor X, (E) protein C, and (F) protein S between INR difference groups. Patients were classified into two groups based on the difference between the CoaguChek XS Plus and ACL TOP 750 INR value cutoff of ≥0.5. Abbreviation: INR, international normalized ratio.

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