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Interpretation of Point-of-care INR Results in Patients Treated with Dabigatran

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Abstract

Background

Point-of-care devices for measurement of the international normalized ratio (INR) are commonly used to monitor therapy and maintain therapeutic levels of anticoagulation in patients treated with vitamin K antagonists. Dabigatran, a new oral, reversible direct thrombin inhibitor approved for stroke prevention in patients with atrial fibrillation does not require routine coagulation monitoring. However, case reports have identified falsely elevated point-of-care INR levels in patients treated with dabigatran using one of these devices (Hemochron). This in vitro study was designed to verify this issue.

Methods

We compared INR levels in whole blood and plasma using a Hemochron Jr. Signature+ point-of-care device (International Technidyne Corporation, Edison, NJ) with routine laboratory monitoring, using blood from healthy volunteers that was spiked with increasing concentrations of dabigatran.

Results

Prothrombin time and INR levels were increased about 2- to 4-fold with the point-of-care device compared with laboratory measures across the plasma dabigatran concentration range 50-1400 ng/mL. At plasma concentrations of dabigatran likely to be observed in patients, at a dose of 150 mg twice daily (60-275 ng/mL), whole blood point-of-care INR values increased from 1.7 to 4.0, versus 1.1 to 1.5 measured with the laboratory coagulometer. Similar differences in prothrombin time were observed in plasma samples.

Conclusions

INR levels in patients taking dabigatran are substantially higher using a Hemochron Jr. point-of-care device compared with laboratory values. We discourage the use of these devices specifically, as well as the use of the INR in general, for measuring the anticoagulant effect of dabigatran.

Section snippets

Methods

The study was approved by a Local Research Ethics Committee, and all 4 subjects (2 male and 2 female) gave written informed consent. Venous blood samples (20 mL in total) were collected from each volunteer into 3.2% sodium citrate tubes, separated into aliquots, spiked with increasing concentrations (50-1400 ng/mL) of dabigatran (Boehringer Ingelheim, Ingelheim, Germany), and incubated at 37°C for at least 5 minutes. Whole blood samples (100 μL) were applied to individual disposable prothrombin

Results

Across the dabigatran concentration range tested, INR levels were consistently higher (by 2- to 4-fold) when measured using the Hemochron Jr. point-of-care device compared with the laboratory-based coagulometer (Figure 1). At representative plasma concentrations of dabigatran, likely to be observed in patients, at a dose of 150 mg twice daily (60-275 ng/mL),3 whole blood point-of-care INR values increased from 1.7 to 4.0, compared with 1.1 to 1.5 when measured with the laboratory coagulometer (

Discussion

The results of this study confirm the previous case reports5, 6 and highlight the risks associated with using INR measurements obtained from point-of-care devices as a basis for clinical decision-making in patients receiving dabigatran. In general, INR levels using the point-of-care device were 2- to 4-fold higher than those measured using routine laboratory monitoring. The cause of elevated measurements with this point-of-care device remains unclear but may be due to lack of calibration of the

References (6)

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Funding: Boehringer Ingelheim.

Conflict of Interest: JvR and AC are employees of Boehringer Ingelheim.

Authorship: All authors had access to the data and played a role in writing this manuscript.

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