تروپونین (ترجمه) troponin

 

Troponin: What Laboratorians Should Know to Manage Elevated Results

FDA, using input provided by Advanced Medical Technology Association (AdvaMed), has developed this document in response to numerous adverse event reports of falsely elevated results sent by manufacturers and users of troponin assays and many published articles related to this subject.

What is the Purpose and Scope of this Communication?

The purpose of this communication is to inform laboratorians about the possibility of falsely elevated troponin results when troponin is used as a cardiac marker, and to provide information as to how to identify and verify cases of suspected falsely elevated results. This communication may also be of interest to cardiologists, primary care physicians, and emergency care physicians. In this document, we use the term “false-positive” troponin test result to refer to cases when the troponin immunoassay result is positive in the absence of acute myocardial infarction (AMI) or any other clinical condition in which troponin markers may be elevated.

This document addresses issues related to false-positive troponin results only when troponin testing is used in the diagnosis of acute myocardial infarction and not when it is used to diagnose other diseases. The information applies to both cardiac troponin I and cardiac troponin T immunoassays since the issue of falsely elevated results applies to both assay systems.

Cardiac troponins are highly sensitive and specific biochemical markers of myocardial cell necrosis and are widely used for the diagnosis of acute myocardial infarction. [1][2] Troponin levels rise and fall with acute myocardial infarction and with other clinical syndromes associated with infiltrative/inflammatory causes of myocyte death.

Troponin testing is subject to analytical interfering factors and assay malfunctions; both may lead to a falsely elevated troponin result. In addition, there are clinical conditions in which the troponin level may rise in the absence of an acute myocardial infarction . Although the elevation of troponin in association with non-AMI is generally rare, it may mislead the clinician to suspect that the patient has an acute myocardial infarction when that is not the case.

Therefore, it is important that laboratorians, working in conjunction with physicians who order the test, are aware of falsely elevated results and non-AMI causes of elevated troponin results in order to assist physicians to properly utilize troponin results in patient management.

Can Results of Different Troponin Assay Systems Be Compared?

No. The results of different troponin assays are not generally comparable. A large variation in cardiac troponin I concentration, in terms of absolute value, may be observed for a given patient specimen with different analytic methods.[3] Until recently, there was no accepted reference standard for troponins. However, a new Standard Reference Material for Human Cardiac Troponin Complex (SRM 2921)[4] has been introduced by the National Institute of Standards and Technology (NIST) which should aid in the future standardization of troponin assays. The SRM 2921 is intended for use in evaluating the accuracy of clinical procedures for the determination of cardiac troponin I in human serum.[4]

The analytical variability among troponin assays is due to the fact that different troponin assays have wide variations in lower detection limits, upper reference limits, diagnostic cut points, assay imprecision (coefficient of variation),[5] and specimen matrices (i.e., serum versus plasma samples). The presence of a large number of manufacturers of troponin assays in the United States market makes standardization more difficult.

What Are the Analytical Interfering Factors That May Lead to Falsely Elevated Troponin Results?

Some of the analytical interfering factors that may lead to falsely elevated troponin results include:[3][6][7]

  • fibrin clots in serum as a result of incompletely clotted specimen, e.g. in patients with coagulopathy or on anticoagulant therapy[8]
  • heterophile antibodies, human anti-animal antibodies[9], rheumatoid factor [10][11], and autoantibodies
  • interference from other endogenous components in the blood such as bilirubin and hemoglobin[12]
  • immunocomplex formation[13]
  • microparticles in specimen
  • high concentration of alkaline phosphatase[14]
  • analyzer malfunction[15]

What Are Interfering Antibodies (Heterophile and Human Anti-Animal) and How Can Laboratorians Address This Issue?

·         Definition and Sources: Circulating heterophile antibodiesi and anti-animal antibodiesii have the potential to interfere with two-site (sandwich) or competitive immunoassays, such as troponin assays, by cross-linking the capture and label antibodies in the absence of specific analyte. [6][16] The estimated prevalence of interfering antibodies in the general population is up to 40% of normal serum samples. [17][18]

Most modern immunoassays contain nonspecific blocker immunoglobulins (which originate from the same species as the analyte-specific antibodies) in order to limit the effect of the interfering antibodies.[19] However, in some instances the blocking proteins can not sufficiently neutralize the interfering antibodies. Thus, analytical errors may occur. In case of troponin assays, the presence of high levels of these antibodies may lead to falsely elevated values.

An individual may acquire these antibodies from a variety of sources including the use of mouse monoclonal antibodies in diagnostic imaging and cancer therapy; exposure to microbial antigens; exposure of veterinarians, farm workers, and food preparers to foreign proteins; the presence of domestic animals in the home; or autoimmune diseases which can give rise to autoantibodies such as rheumatoid factor.

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