Interference in point-of-care international normalized ratio monitoring in patients with lupus anticoagulant is correlated with anti-β2-glycoprotein I antibody titers

Abstract

Background: Patients with antiphospholipid syndrome (APS) receive anticoagulant therapy with vitamin K antagonists (VKAs) to prevent recurrent thrombosis. VKA treatment requires strict monitoring with an international normalized ratio (INR). It is known that lupus anticoagulants (LAs) can lead to elevated INR results with point-of-care-testing (POCT) devices, which could result in inadequate adaptation of anticoagulant therapy.

Objective: To determine discrepancies between POCT-INR and laboratory-INR in patients who are LA-positive on VKA therapy.

Methods: Paired INR testing was performed with 1 POCT device (CoaguChek XS) and 2 laboratory assays (Owren and Quick method) in 33 patients with LA-positive APS on VKA in a single-center cross-sectional study. Patients were tested for anti-β2-glycoprotein I, anticardiolipin, and antiphosphatidylserine/prothrombin immunoglobulin (Ig) G and IgM antibodies. Agreement between assays was evaluated with Spearman's correlation, Lin's correlation coefficient, and Bland-Altman plots. Agreement limits were considered satisfactory if differences were ≤20% as determined by the Clinical and Laboratory Standards Institute.

Results: We found poor agreement between POCT-INR and laboratory-INR based on Lin's concordance correlation coefficient (ρ_c) of 0.42 (95% CI, 0.26-0.55) between POCT-INR and Owren-INR, a ρ_c of 0.64 (95% CI, 0.47-0.76) between POCT-INR and Quick-INR, and a ρ_c of 0.77 (95% CI, 0.64-0.85) between Quick-INR and Owren-INR. High anti-β2-glycoprotein I IgG antibody titers correlated with INR disagreement between POCT-INR and laboratory-INR.

Conclusion: There is a disagreement between INR values measured with the CoaguChek XS and laboratory-INR in a proportion of patients with LA. Consequently, laboratory-INR monitoring should be preferred over POCT-INR monitoring in patients with LA-positive APS, especially in patients with high anti-β2-glycoprotein IgG antibody titers.

Keywords: anticoagulants; international normalized ratio; lupus coagulation inhibitor; point-of-care testing; warfarin.

Figure 1

Scatter plots showing the correlation between the different international normalized ratio (INR) assays. (A) Point-of-care testing (POCT)-INR vs Owren-INR, (B) POCT-INR vs Quick-INR, and (C) Owren-INR vs Quick-INR. Dashed line represents 45° line through origin. Regression line with 95% CI is shown in blue.

Figure 2

Bland–Altman plots showing the agreement between different international normalized ratio (INR) assays. Absolute differences (A–C) and relative differences (D–F) between INR assays were plotted on the y-axis and average INR of 2 methods on the x-axis. Horizontal line represents median, dotted line represents limits of agreement (calculated as 2.5th and 97.5th percentile), dashed line represents agreement limits as determined by the Clinical and Laboratory Standards Institute [27].