5-Minute Point-of-Care Anti-Factor Xa Test for Emergent Patient Management

ABSTRACT
We are proposing to develop a multiplexed point-of-care anti-factor Xa (anti-Xa) and hemoglobin test to
guide emergent management of bleeding and strokes in patients on anti-Xa direct oral anticoagulants (DOACs).
This includes guiding appropriate treatment with andexanet alfa (andexanet, tradename ANDEXXA) during
bleeds or thrombolytics for acute ischemic stroke (AIS). In this Direct-to-Phase II (D2P2) effort, we will
leverage our proprietary CE-marked FXa fluorogenic substrate and our rHEALTH point-of-care device
and app to develop a point-of-care (POC) test that yields results for both drug-specific anti-Xa activity
and hemoglobin. The CLIA-waivable approach will feature a 5-minute turnaround time, from sample collection
to result, delivering results 10x faster than any current STAT central lab test. This would lead to quicker delivery
of life-saving interventions. Currently about 16 million individuals are on direct oral anticoagulants, predominantly
for nonvalvular atrial fibrillation, and ~500,000 per year are hospitalized with bleeds or breakthrough strokes.
Proper therapeutic treatment require emergent and rapid measurement of anti-Xa activity.
In preliminary Phase I-like work, we have developed three innovations: (1) an ultra-rapid anti-Xa
assay based on our CE-marked FXa substrate, (2) a 5-minute sample-to-answer 4D microfluidic cartridge
that carries out sequential steps of our anti-Xa assay, and (3) an app-connected point-of-care device that
returns both the anti-Xa and hemoglobin values for venous or capillary blood samples. Here we propose
to leverage this work to develop a system that will rigorously test thousands of cartridges across three aims: (1)
Assess accuracy and precision of all consumable steps and improve robustness where needed, (2) Assess
performance of various anti-Xa drugs on spiked whole blood samples and develop drug-specific controls and
calibrators, and (3) Characterize the integrated anti-Xa monitoring device, app, and consumable for analytical
precision, interferences, ranges, and limit of detection. Upon completion of this D2P2, we will commence a 510k
clinical validation study, as required for FDA clearance.
The success of developing a 5-minute anti-Xa test will allow for 10x faster responses to guide emergency
management of patients and bring a much-needed capability to the point-of-care. A patient’s presenting anti-Xa
drug levels can vary widely, based on their peak and trough timing, drug dosage, drug clearance rate, and
bioavailability. A 5-minute anti-Xa test allows guiding immediate management and timely follow-on
measurements to allow tailored therapy. The rapid and cost-effective nature of the device will allow its use in
ambulances, emergency rooms, and surgical suites. The simultaneous reporting of hemoglobin gives treating
clinicians immediate information about the status of blood loss in the event of bleeding. The results of our efforts
will be a rapid, cost-effective, monitoring device, consumable, app, and controls that will provide an urgently
needed resource in light of recent developments in anti-Xa therapies.

Grant Number: 5R44HL170817-02
NIH Institute/Center: NIH
Principal Investigator: Eugene Chan