D-dimer, troponin, and nt-probnp for pulmonary embolism

Abstract

The present invention relates to a method of diagnosing acute pulmonary embolism (PE) in a subject including a) determining the amount of fibrin-fibrinogen degradation products, in particular D-dimer in a sample of the subject; b) determining the amount of a natriuretic peptide in a sample of the subject; c) determining the amount of a cardiac troponin in a sample of the subject; and d) comparing the amounts determined in steps a) to c) to reference amounts, thereby establishing the diagnosis. Included is also a method of deciding on a therapy of a subject diagnosed with PE and a method of monitoring the therapy.

1 . A method of classifying a subject suffering from pulmonary embolism (PE) into one of a PE severity risk group selected from, Risk Group I (symptomatic non-massive PE, haemodynamic stable without right ventricular dysfunction, systolic arterial pressure >100 mmHg); Risk Group II (submassive PE, haemodynamic stable with right ventricular dysfunction); Risk Group III (massive PE, shock and hypotension, systolic arterial pressure <100 mmHg, heart rate >100/min; and Risk Group IV (resuscitation necessary), the method comprising the steps of:
 measuring an amount of D-dimer in a portion of a sample from the subject;   measuring an amount of a natriuretic peptide in a portion of the sample from the subject;   measuring an amount of a cardiac troponin in a portion of the sample from the subject;   comparing the amount of D-dimer, the natriuretic peptide, and the cardiac troponin measured in said steps of measuring, respectively, to reference amounts for D-dimer, the natriuretic peptide, and the cardiac troponin, respectively; and   classifying the subject into one of the PE severity risk groups based on said step of comparing.   
     
     
         2 . The method according to  claim 1 , wherein the natriuretic peptide is NT-pro BNP and the cardiac troponin is troponin T. 
     
     
         3 . The method of  claim 2 , wherein
 amounts of D-dimer from 500 to less than 2000 μg/L, troponin T less than 0.03 ng/ml, and NT-proBNP less than 500 pg/ml are indicative for PE severity risk group I;   amounts of D-dimer from 2000 to less than 6000 μg/L, troponin T less than 0.03 ng/ml, and NT-proBNP less than 500 pg/ml are indicative for PE severity risk group II;   amounts of D-dimer from 6000 to 12000 μg/L, troponin T greater than 0.1 ng/ml, and NT-proBNP equal to or greater than 500 pg/ml are indicative for PE severity risk group III; and   amounts of D-dimer greater than 12000 μg/L, troponin T greater than 1.0 ng/ml, and NT-proBNP greater than 5000 pg/ml are indicative for PE severity risk group IV.   
     
     
         4 . The method according to  claim 1 , wherein the sample is blood, serum, or plasma. 
     
     
         5 . The method according to  claim 1 , wherein the subject is a human. 
     
     
         6 - 7 . (canceled) 
     
     
         8 . A method of monitoring a therapy of a subject suffering from pulmonary embolism (PE), wherein the therapy is one of medication with heparin, urokinase, streptokinase, recombinant tissue plasminogen activators, and embolectomia, the method comprising the steps of:
 measuring an amount of D-dimer in a portion of a sample from the subject;   measuring an amount of a natriuretic peptide in a portion of the sample from the subject;   measuring an amount of a cardiac troponin in a portion of the sample from the subject;   comparing the amount of D-dimer, the natriuretic peptide, and the cardiac troponin measured in said steps of measuring, respectively, to reference amounts for D-dimer, the natriuretic peptide, and the cardiac troponin, respectively; and   identifying the subject as being suitably treated based on said step of comparing.   
     
     
         9 - 10 . (canceled) 
     
     
         11 . A method of diagnosing a subject as suffering from acute pulmonary embolism (PE), the method comprising the steps of:
 measuring an amount of D-dimer in a portion of a sample from the subject;   measuring an amount of a natriuretic peptide in a portion of the sample from the subject;   measuring an amount of a cardiac troponin in a portion of the sample from the subject;   comparing the amount of D-dimer, the natriuretic peptide, and the cardiac troponin measured in said steps of measuring, respectively, to reference amounts for D-dimer, the natriuretic peptide, and the cardiac troponin, respectively; and   diagnosing the subject as suffering from acute pulmonary embolism based on said step of comparing.   
     
     
         12 . The method according to  claim 11 , wherein the reference amount for D-dimer is 500 μg/L, wherein the cardiac troponin is troponin T and the reference amount for troponin T is 0.03 ng/ml, and wherein the natriuretic peptide is NT-proBNP and the reference amount for NT-proBNP is 125 pg/ml. 
     
     
         13 . The method according to  claim 1 , wherein the natriuretic peptide is selected from the group consisting of NT-proBNP, BNP, and NT-proANP and wherein the cardiac troponin is selected from the group consisting of troponin T and troponin I. 
     
     
         14 . The method according to  claim 1 , wherein said step of measuring the amount of D-dimer comprises contacting the portion of the sample, in vitro, with a ligand having specific binding affinity for D-dimer polypeptide. 
     
     
         15 . The method according to  claim 14 , wherein the ligand is one of an antibody, a nucleic acid, and a polypeptide receptor. 
     
     
         16 . The method according to  claim 14 , wherein said step of measuring the amount of D-dimer further comprises a second ligand having specific binding affinity for the ligand having specific binding affinity for D-dimer polypeptide. 
     
     
         17 . The method according to  claim 16 , wherein the second ligand includes a tag consisting of one of an enzymatically active label, a fluorescent label, a radioactive label, a biotin label, and a streptavidin label. 
     
     
         18 . The method according to  claim 2 , wherein said step of measuring the amount of troponin T comprises a ligand having specific binding affinity for troponin T polypeptide. 
     
     
         19 . The method according to  claim 2 , wherein said step of measuring the amount of NT-pro BNP comprises a ligand having specific binding affinity for NT-pro BNP. 
     
     
         20 . The method according to  claim 8 , wherein the natriuretic peptide is selected from the group consisting of NT-proBNP, BNP, and NT-proANP and wherein the cardiac troponin is selected from the group consisting of troponin T and troponin I. 
     
     
         21 . The method according to  claim 20 , the natriuretic peptide is NT-pro BNP and the cardiac troponin is troponin T. 
     
     
         22 . The method according to  claim 21 , wherein:
 said step of measuring the amount of D-dimer comprises contacting the portion of the sample, in vitro, with a ligand having specific binding affinity for D-dimer polypeptide;   said step of measuring the amount of troponin T comprises a ligand having specific binding affinity for troponin T polypeptide; and   said step of measuring the amount of NT-pro BNP comprises a ligand having specific binding affinity for NT-pro BNP.   
     
     
         23 . The method according to  claim 11 , the natriuretic peptide is NT-pro BNP and the cardiac troponin is troponin T. 
     
     
         24 . The method according to  claim 23 , wherein:
 said step of measuring the amount of D-dimer comprises contacting the portion of the sample, in vitro, with a ligand having specific binding affinity for D-dimer polypeptide;   said step of measuring the amount of troponin T comprises a ligand having specific binding affinity for troponin T polypeptide; and   said step of measuring the amount of NT-pro BNP comprises a ligand having specific binding affinity for NT-pro BNP.