NT-pro ANP and SFlt-1 For The Differentiation Between Circulatory And Ischemic Events

Abstract

The present disclosure relates to the field of laboratory diagnostics. The present disclosure provides means and methods for differentiating between an acute circulatory event and an ischemic event, as the cause underlying an acute medical event of a patient.

1 : A method for rapidly differentiating whether an acute medical event in an emergency patient is associated with
 (i) a circulatory complication;   (ii) an ischemic complication; or   (iii) both a circulatory complication and an ischemic complication;   
       the method comprising the steps of
 a) determining the amount of an ANP-type peptide in a serum or plasma sample from a subject suffering from an acute medical event; 
 b) determining the amount of sFlt-1 peptide in a serum or plasma sample from said subject suffering from an acute medical event; 
 c) comparing the amounts of the ANP-type peptide and the sFlt-1 peptide measured in steps a) and b) to reference amounts for ANP-type peptide and sFlt-1 peptide, respectively; and 
 d) establishing a differentiation based on the results of c) by: 
 (i) diagnosing an acute medical event associated with a circulatory complication if an increased level of the ANP-type peptide relative to the reference amount is determined, 
 (ii) diagnosing an acute medical event associated with an ischemic complication if an increased level of sFlt-1 relative to the reference amount is determined, and 
 (iii) diagnosing an acute medical event associated with both a circulatory complication and an ischemic complication if an increased level of the ANP-type peptide relative to the reference amount and an increased level of sFlt-1 relative to the reference amount is determined. 
 
     
     
         2 : The method of  claim 1 , wherein the ischemic complication comprises systolic blood pressure of less than 80 mmHg. 
     
     
         3 : The method of  claim 1 , wherein the acute medical event is heart failure, lung failure or renal failure. 
     
     
         4 : The method of  claim 1 , wherein the ischemic complication is an acute hypoxia of the spleen, the heart, the kidney, the bowel or the limbs. 
     
     
         5 : The method of  claim 1 , wherein the ANP-type peptide is NT-proANP. 
     
     
         6 : The method of  claim 5 , wherein the reference amount for NT-proANP is about 2500 pg/ml. 
     
     
         7 : The method of  claim 1 , wherein the reference amount for sFlt-1 peptide is about 500 pg/ml. 
     
     
         8 : The method of  claim 1 , further comprising the step of obtaining a serum or plasma sample from a subject suffering from an acute medical event before step a). 
     
     
         9 : The method of  claim 1 , wherein the determining step a) is performed on a portion of a serum or plasma sample from said subject suffering from an acute medical event, and wherein step b) is performed on a further portion of the same serum or plasma sample. 
     
     
         10 : The method of  claim 1 , wherein step a) comprises contacting, in vitro, said serum or plasma sample from said subject with an antibody immunoreactive for an NT-proANP peptide. 
     
     
         11 : The method of  claim 10 , wherein step a) requires contacting said sample with two antibodies immunoreactive for different portions of the NT-proANP peptide, wherein the first antibody is a polyclonal sheep NT-proANP-specific antibody and the second antibody is conjugated with horseradish peroxidase (HRP). 
     
     
         12 : The method of  claim 10 , wherein the antibody in step a) is bound to a microtiterstrip. 
     
     
         13 : The method of  claim 1 , wherein step b) comprises contacting, in vitro, the serum or plasma sample with two antibodies immunoreactive for different portions of a sFlt-1 peptide, wherein the first antibody has one of a biotin and a streptavidin linked thereto and wherein the second antibody has a Tris (2,2′-bipyridyl) ruthenium (H)-complex linked thereto. 
     
     
         14 : A device for rapidly differentiating whether an acute medical event in an emergency patient is associated with
 (i) a circulatory complication;   (ii) an ischemic complication, or   (iii) both a circulatory complication and an ischemic complication;   
       said device comprising
 a) an analyzing unit for determining the amount of an ANP-type peptide in a serum or plasma sample of said emergency patient; 
 b) an analyzing unit for determining the amount of sFlt-1 in a serum or plasma sample from said emergency patient; 
 c) a computer unit for comparing the measured amounts of the ANP-type peptide and sFlt-1 to reference amounts for ANP-type peptide and sFlt-1 peptide, respectively; and 
 a computer unit for establishing a diagnosis based on the results of the comparison, wherein 
 (i) an acute medical event associated with a circulatory complication is diagnosed if an increased level of the ANP-type peptide relative to the reference amount is determined, 
 (ii) an acute medical event associated with an ischemic complication is diagnosed if an increased level of sFlt-1 relative to the reference amount is determined, and 
 (iii) an acute medical event associated with both a circulatory complication and an ischemic complication is diagnosed if an increased level of the ANP-type peptide relative to the reference amount and an increased level of sFlt-1 relative to the reference amount is determined. 
 
     
     
         15 : The device of  claim 14 , wherein the ANP-type peptide is proANP.