Detection and classification of an anticoagulant using a clotting assay

Patent metadata

Field	Value
Publication number	US-10954549-B2
Application number	US-201916674334-A
Country	US
Kind code	B2
Filing date	Nov 5, 2019
Priority date	Jul 31, 2014
Publication date	Mar 23, 2021
Grant date	Mar 23, 2021

Abstract

In some embodiments, the invention provides methods for detecting and/or classifying an anticoagulant at a therapeutically relevant amount or higher in a patient, including subjecting a sample of a control blood component (known not to contain the anticoagulant) to a clotting assay in the presence of a Factor Xa reagent to obtain a control clotting measurement; and subjecting a sample of a blood component from a patient suspected of having the anticoagulant to the clotting assay in the presence of the Factor Xa reagent to obtain a patient clotting measurement, wherein the patient clotting measurement sample greater than the control clotting measurement indicates the presence of the anticoagulant at a therapeutically relevant amount or higher in the patient. In some embodiments, the invention includes methods for classifying an anticoagulant as an anti-Factor Xa or a direct thrombin inhibitor anticoagulant using a clotting assay in the presence of an ecarin reagent.

First claim

What is claimed is:

1. A method for treating a patient suspected of having either an anti-Factor Xa or a direct thrombin inhibitor (DTI) anticoagulant at a therapeutically relevant amount or higher, the method comprising:
a. detecting the anticoagulant by:
i. obtaining a first sample of a blood component from the patient,
ii. performing a first viscoelastic analysis clotting assay in the presence of a Factor Xa reagent on the first sample of a blood component from the patient to obtain a patient Factor Xa clotting measurement;
wherein the patient Factor Xa clotting measurement that is greater than a control Factor Xa clotting measurement indicates the presence of the anti-Factor Xa anticoagulant or the presence of the DTI anticoagulant at a therapeutically relevant amount or higher in the patient,
wherein the control Factor Xa clotting measurement was obtained by performing a viscoelastic analysis clotting assay in the presence of the Factor Xa reagent on a control sample of a blood component lacking an anticoagulant, and
wherein the patient Factor Xa clotting measurement less than or equal to the control Factor Xa clotting measurement indicates the absence of both the anti-Factor Xa anticoagulant and the DTI anticoagulant at a therapeutically relevant amount or higher in the patient; and

b. if the presence of the anti-Factor Xa anticoagulant or the presence of the DTI anticoagulant at a therapeutically relevant amount or higher in the patient is detected, classifying the anticoagulant by:
i. obtaining a second sample of a blood component from the patient identified as having an anticoagulant at a therapeutically relevant amount or higher;
ii. performing a second viscoelastic analysis clotting assay in the presence of an ecarin reagent on the second sample of a blood component from the patient to obtain a patient ecarin clotting measurement;
wherein a patient ecarin clotting measurement that is greater than a control ecarin clotting measurement identifies the detected anticoagulant as the DTI anticoagulant in the patient, and wherein a patient ecarin clotting measurement less than or equal to the control ecarin clotting measurement identifies the detected anticoagulant as the anti-Factor Xa anticoagulant in the patient,
wherein the control ecarin clotting measurement was obtained by performing a viscoelastic clotting assay on a control sample of a blood component lacking an anticoagulant in the presence of an ecarin reagent; and

administering to the patient identified as having a DTI anticoagulant a therapeutically relevant amount of a reversal agent that reverses the DTI anticoagulant, or administering to the patient identified as having an anti-Factor Xa a therapeutically relevant amount of a reversal agent that reverses the anti-Factor Xa anticoagulant.

2. The method of claim 1 , wherein the viscoelastic analysis is performed using a container containing the sample on an interior of the container.

3. The method of claim 2 , wherein the viscoelastic analysis is performed using the container and a pin, wherein the pin moves relative to the container or the container moves relative to the pin.

4. The method of claim 2 , wherein the container lacks a bottom surface.

5. The method of claim 1 , wherein the patient is a human.

6. The method of claim 1 , wherein the patient is undergoing a condition selected from the group consisting of surgery, trauma, bleeding, stroke and a thromboembolic event.

7. The method of claim 1 , wherein the anticoagulant is an oral anticoagulant.

8. The method of claim 1 , wherein the control Factor Xa clotting measurement is a range, average or median of at least two Factor Xa clotting measurements of at least two control blood components known to lack the anticoagulant.

9. The method of claim 1 , wherein the control ecarin clotting measurement is a range, average or median of at least two ecarin clotting measurements of at least two control blood components known to lack the anticoagulant.

10. The method of claim 1 , wherein the patient Factor Xa clotting measurement that is at least 1.25 times greater than the control Factor Xa clotting measurement indicates the presence of the anti-Factor Xa anticoagulant or the presence of the DTI anticoagulant at a therapeutically relevant amount or higher in the patient.

11. The method of claim 1 , wherein a patient ecarin clotting measurement that is at least 1.25 times greater than the control ecarin clotting measurement identifies the detected anticoagulant as the DTI anticoagulant in the patient.

12. The method of claim 1 , wherein the reversal agent that reverses the DTI anticoagulant is selected from the group consisting of prothrombin complex concentrates and idarucizumab.

13. The method of claim 1 , wherein the reversal agent that reverses the anti-Factor Xa anticoagulant is selected from the group consisting of prothrombin complex concentrates and andexanet alfa.

14. A method for detecting and/or classifying an anticoagulant at a therapeutically relevant amount or higher in a patient suspected of having an anticoagulant comprising:
a) subjecting a first sample of a blood component from the patient to a clotting assay in the presence of a Factor Xa reagent to obtain a patient Factor Xa clotting measurement,
b) subjecting a second sample of the blood component from the patient to a clotting assay in the presence of an ecarin reagent to obtain a patient ecarin clotting measurement; and
c) comparing the patient Factor Xa clotting measurement to a control Factor Xa clotting measurement from a control blood component known to lack the anticoagulant and comparing the patient ecarin clotting measurement to a control ecarin clotting measurement from the control blood component;
wherein the patient ecarin clotting measurement greater than the control ecarin clotting measurement identifies the presence of the anticoagulant at or above a therapeutically relevant amount in the patient and identifies the anticoagulant as a direct thrombin inhibitor (DTI), and wherein the patient Factor Xa clotting measurement of greater than the control Factor Xa clotting measurement identifies the presence of the anticoagulant at or above a therapeutically relevant amount in the patient and identifies the anticoagulant as an anti-Factor Xa anticoagulant, and wherein the patient Factor Xa clotting measurement less than or equal to the control Factor Xa clotting measurement identifies absence of any anticoagulant at or above a therapeutically relevant amount in the patient, and
wherein the patient identified as comprising the presence of the DTI anticoagulant at a therapeutically relevant amount or higher is administered a therapeutically relevant amount of a reversal agent that reverses the DTI anticoagulant and wherein the patient identified as comprising the presence of the anti-Factor Xa anticoagulant at a therapeutically relevant amount or higher is administered a therapeutically relevant amount of a reversal agent that reverses the anti-Factor Xa anticoagulant.

15. The method of claim 14 , wherein the clotting assay is a viscoelastic analysis clotting assay.

16. The method of claim 15 , wherein the viscoelastic analysis is performed using a container containing the sample on an interior of the container.

17. The method of claim 14 , wherein the patient is undergoing a condition selected from the group consisting of surgery, trauma, bleeding, stroke and a thromboembolic event.

18. The method of claim 14 , wherein the control Factor Xa clotting measurement is a range, average or median of at least two F

Assignees

• Haemonetics Corp

Inventors

• Zaman Fowzia S
• DOUBLEDAY Marc

Classifications

• G01N33/86 Primary

  involving blood coagulating time {or factors, or their receptors} · CPC title

• C12Q1/56 Primary

  involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen · CPC title

• G01N2333/96444

  Factor X (3.4.21.6) · CPC title

• G01N11/00

  Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties · CPC title