BEST PRACTICES :: UNDERSTANDING ELEVATED TROPONIN
Assay-related cardiac troponin elevations As with many laboratory assays, interferences may exert effects that assay design cannot mitigate or at least fully mitigate. Some of these interferences affect all assays, and some may affect only certain assays. Three common inter- ferences that are regularly tested make up the HIL index, or hemolysis (hemoglobin), icterus (bilirubin) and lipemia (triglycerides/Intralipid; also called turbidity). As hemolysis increases, hs-cTnI and hs-cTnT results have been reported to increase (or decrease) for susceptible assays.8-10
Laboratories
should seek out the assay Instructions for Use (IFU) from their manufacturer to understand the HIL interference criteria and limits for their assay. Various types of endogenous antibodies may also affect cTn
results, including heterophile antibodies, autoantibodies, and macrotroponin. Anti-troponin autoantibodies likely cause a falsely low result, and therefore are less concerning from the perspective of elevated cTn in the differential diagnosis of acute MI. Heterophile antibodies and macrotroponin, on the other hand, may cause falsely elevated (or falsely depressed) results. Heterophile antibodies are produced against poorly defined immunoglobulins, and have weak avidity to multi-specific an- tigens, generated from any number of environmental sources, certain infections, or some treatments. Prevalence estimates vary widely. When present in a patient sample, heterophile antibodies can cause falsely elevated results by cross-linking of the heterophile antibodies with the cTn antibodies used in the assay architecture. As has been reported since the late 1990s, this may cause a falsely elevated result, which has been reported in multiple case studies and reviewed.11,12
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Macrotroponin interference can occur when autoantibodies bind cTn to make a complex. These large immunoglobulin-troponin complexes have reduced clearance and can affect assays differently and inconsistently. In other words, a particular assay may be affected by macrotroponin in one sample, but not be affected by macro- troponin in another sample.13
the 99th percentile, and sometimes very elevated, as demonstrated in a recent case study.14
The results are often elevated above Prevalence of macrotroponin has been
suggested to be 5% or less,15 but our knowledge of prevalence,
causes, and other aspects is currently limited. Another potential cause of elevated cTn results is rheumatoid factor (RF), an interferent that may affect various analytes on immunoassay analyzers. Rheumatoid factor may be elevated in autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosus, especially when the disease is active, such that the elevation is significant enough to cause an interference and false positive cTn. RF can cause significantly elevated results high above the 99th percentile URL.16 In addition to those interfering factors covered here, other factors
that may cause falsely elevated cTn results should be considered when interpreting or investigating cTn elevations, including fibrin clots, sample type, time of day of blood draw (which has been reported to affect cTnT), and transportation of specimens.17-20
Conclusion The proper interpretation of cTn elevations in the context of acute myocardial ischemia/infarction requires careful consideration of potential preanalytical and clinical causes of cTn elevation. In addition to many types of preanalytical factors, there may be analytical and clinical causes of troponin elevations, which
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