Detection of Reversal of an Anticoagulant Using a Clotting Assay

Abstract

In some embodiments, the invention provides methods for detecting the reversal 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 an ecarin reagent to obtain a control ecarin clotting measurement; 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 Factor Xa clotting measurement; subjecting a sample of a blood component from a patient suspected to contain a reversal agent to a clotting assay in the presence of the ecarin reagent to obtain a patient ecarin clotting measurement; subjecting a sample of a blood component from the patient suspected to contain the reversal agent to a clotting assay in the presence of the Factor Xa reagent to obtain a patient Factor Xa clotting measurement; and comparing the control ecarin clotting measurement to the patient ecarin clotting measurement and comparing the control Factor Xa clotting measurement to the patient Factor Xa measurement.

What is claimed is: 
     
         1 . A method for detecting reversal of an anticoagulant at a therapeutically relevant amount or higher in a patient having an anticoagulant, the method comprising:
 (a) subjecting a sample of a control blood component known to lack the anticoagulant to a clotting assay in the presence of an ecarin reagent to obtain a control ecarin clotting measurement;   (b) subjecting a sample of the control blood component known to lack the anticoagulant to a clotting assay in the presence of a Factor Xa reagent to obtain a control Factor Xa clotting measurement;   (c) subjecting a sample of a blood component from a patient suspected to contain a reversal agent to a clotting assay in the presence of the ecarin reagent to obtain a patient ecarin clotting measurement;   (d) subjecting a sample of the blood component from the patient suspected to contain the reversal agent to a clotting assay in the presence of the Factor Xa reagent to obtain a patient Factor Xa clotting measurement; and   (e) comparing the control ecarin clotting measurement to the patient ecarin clotting measurement and comparing the control Factor Xa clotting measurement to the patient Factor Xa measurement,   wherein the patient ecarin clotting measurement less than or equal to the control ecarin clotting measurement and/or the patient Factor Xa clotting measurement less than or equal to the control Factor Xa clotting measurement identifies the blood component from the patient as having a reversal agent that has reversed the anticoagulation activity of the anticoagulant in the patient.   
     
     
         2 . The method of  claim 1 , wherein the clotting assay is selected from the group consisting of a prothrombin time assay, an activated partial thromboplastin time assay, an activated clotting time assay, and a viscoelastic analysis clotting assay. 
     
     
         3 . The method of  claim 2 , wherein the clotting assay is a viscoelastic analysis clotting assay and wherein the viscoelastic analysis is performed using a container containing the sample on an interior of the container. 
     
     
         4 . The method of  claim 3 , wherein the viscoelastic analysis is performed using the container and a pin, wherein the pin moves relative to the container or wherein the container moves relative to the pin. 
     
     
         5 . The method of  claim 3 , wherein the container lacks a bottom surface. 
     
     
         6 . The method of  claim 1 , wherein the patient is a human. 
     
     
         7 . The method of  claim 1 , wherein the patient is undergoing a condition selected from the group consisting of surgery, trauma, bleeding, stroke, a thromboembolic event, and combinations thereof. 
     
     
         8 . The method of  claim 1 , wherein the anticoagulant is an oral anticoagulant. 
     
     
         9 . The method of  claim 1 , wherein the control Factor Xa clotting measurement is a range of at least two Factor Xa clotting measurements of at least two control blood components known to lack the anticoagulant, and wherein the control ecarin clotting measurement is a range 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 reversal agent reverses the anticoagulation activity of a direct thrombin inhibitor. 
     
     
         11 . The method of  claim 1 , wherein the reversal agent reverses the anticoagulation activity of a Factor Xa inhibitor. 
     
     
         12 . The method of  claim 1 , wherein the reversal agent is andexanet. 
     
     
         13 . The method of  claim 1 , wherein the reversal agent is a prothrombin complex concentrate. 
     
     
         14 . The method of  claim 1 , wherein the reversal is a complete reversal of the anticoagulation activity of the anticoagulant in the patient. 
     
     
         15 . The method of  claim 1 , wherein the reversal is a partial reversal of the anticoagulation activity of the anticoagulant in the patient. 
     
     
         16 . The method of  claim 8 , wherein the oral anticoagulant is selected from the group consisting of a direct thrombin inhibitor, a Factor Xa inhibitor, and combinations thereof. 
     
     
         17 . The method of  claim 1 , wherein the reversal agent is idarucizumab.