Comparison of a chromogenic factor X assay with international normalized ratio for monitoring oral anticoagulation therapy

Abstract

The purpose of the present study was to compare the international normalized ratio with a chromogenic factor X (CFX) assay for monitoring patients on oral anticoagulant therapy using the DiaPharma CFX method on a STA-R Evolution coagulation analyzer. International normalized ratio values were correlated with the CFX for determining normal, subtherapeutic, therapeutic and supratherapeutic ranges for these patients. Specimens were analyzed and grouped as normal or patients on oral anticoagulant therapy with international normalized ratios of less than 2.0, 2.0-3.0, and more than 3.0. Three hundred and nine randomly selected oral anticoagulant therapy patients were tested. The range of international normalized ratio and CFX in oral anticoagulant therapy patients was 0.92-12.76 and 9-132%, respectively. CFX was inversely related to international normalized ratio; R = 0.964 (P < 0.0001) (CFX = 13.2 + (5.3/international normalized ratio) + (81.3/international normalized ratio). Results by group were as follows: normal (n = 30), CFX range 72-131%, mean CFX 96%; international normalized ratio less than 2.0 (n = 70), CFX range 32-132%, mean CFX 53%; international normalized ratio 2.0-3.0 (n = 135), CFX range 18-48%, mean CFX 28%; international normalized ratio more than 3.0 (n = 104), CFX range 9-46%, mean CFX 21%. Sensitivity and specificity crossed at a CFX of 35.5%, which yielded a sensitivity of 91.7% and a specificity of 91.9% for discriminating international normalized ratio of at least 2.0. Area under the curve on receiver-operator curve using international normalized ratio was 0.984 (P < 0.001). In this randomly selected group of oral anticoagulant therapy patients and normal individuals at varying levels of anticoagulation, CFX correlated well with international normalized ratio as determined by R = 0.964. The data suggests that the CFX can be a useful tool for monitoring oral anticoagulation in patient populations in which confounders to international normalized ratio may be present. Further investigation with the use of CFX for monitoring is warranted in large patient populations on oral anticoagulant therapy, including follow-up for clinical outcomes.

Thrombin generation and factor X assays for the assessment of warfarin anticoagulation in thrombotic antiphospholipid syndrome

“…This has been suggested by several authors, although an optimal approach has not been established [8][9][10][11]31]. In our study, as expected, there were strong negative correlations between FX levels and INR, regardless of the PT reagent, and the observed FX therapeutic range in the non-APS patients within a range of 2.0-3.0 was in accordance with a previously reported range [11].…”

“…This has been suggested by several authors, although an optimal approach has not been established [8][9][10][11]31]. In our study, as expected, there were strong negative correlations between FX levels and INR, regardless of the PT reagent, and the observed FX therapeutic range in the non-APS patients within a range of 2.0-3.0 was in accordance with a previously reported range [11]. FX levels for APS patients within this range were similar to those seen in the non-APS patients, supporting the view that the assay is potentially useful as an independent marker of anticoagulant intensity in APS patients.…”

“…This may influence the management of warfarin anticoagulation, particularly when baseline PT measurements are not available prior to commencement of anticoagulation [7]. Factor X (FX) coagulation [8,9] and amidolytic assays [10,11] have been proposed for monitoring warfarin anticoagulation in patients who are difficult to manage by PT/INR.…”

Monitoring anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome

“…Considering the relative concentrations of factor VII and factor X in plasma as well as the significant differences in half-lives of these two vitamin K-dependent clotting factors, it stands to reason that VKA might have a greater impact on a patient's plasma factor VII than factor X concentrations. However, a good agreement between INR and CFX values has been demonstrated [20,21], and a chromogenic factor X assay is the most frequently used alternative to monitor VKA therapy in patients suspected of having a falsely elevated INR. Third, we cannot exclude that occasional interference of LA may lead to an increased false INR in individual patients.…”

Relationship between chromogenic factor X and international normalized ratio differs during early warfarin initiation compared with chronic warfarin administration

“…The chromogenic Factor X assay (CFX) is used to monitor warfarin therapy in patients with international normalized ratio (INR) values falsely elevated due to a lupus anticoagulant or direct thrombin inhibitor (DTI) therapy [1][2][3][4]. Therapeutic CFX activity, corresponding to an INR range of 2.0-3.0, is approximately 40-20% in patients on chronic, steady-state warfarin therapy [1,3].…”