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Letters |
Department of Laboratory Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
aAuthor for correspondence. Fax 81-3- 3359-6963; e-mail hkikuchi{at}sc.itc.keio.ac.jp.
To the Editor:
Triaging of patients with chest pain to rule out acute myocardial infarction is important. Myoglobin is thought to be an effective marker for this purpose in the early hours after the onset of symptoms because it is released into the blood shortly after myocardial damage (1)(2)(3). The Cardiac Reader (Roche) provides a platform for the quantitative immunologic measurement of whole-blood myoglobin. The measuring range of the Cardiac Reader for myoglobin is 30–700 µg/L, and the upper reference limit is 80 µg/L. In a previous study, the within-series CV (the mean value of 20 within-run CVs with 20 instruments) was 5–10% and was almost constant throughout the measuring range (4). The assay system is thought to be suitable for near-patient use because of its easy operation and the short assay time.
We observed two cases whose blood myoglobin concentrations showed falsely low values with this method. Case A was an 84-year-old male in cardiogenic shock attributable to acute myocardial infarction who had a percutaneous transluminal coronary angioplasty immediately after arrival. On day 2 after admission, the blood myoglobin concentration on the Reader was 357 µg/L. The cardiac troponin T concentration measured simultaneously was above the upper limit of linearity (>2.0 µg/L). We noted the discrepancy between these results. Because the myoglobin concentration was above the cutoff but not as high as expected, a "hook effect" of myoglobin was suspected. To confirm this suspicion, we diluted the sample 50- and 100-fold with the blood from a healthy individual whose blood myoglobin concentration was <30 µg/L and reassayed the dilutions with the Cardiac Reader. The myoglobin concentrations in these diluted samples were above the upper limit of the system and 376 µg/L, respectively (Table 1
, Case A). These results suggested that the initial result for the undiluted sample was falsely low because of the hook phenomenon at high concentrations of myoglobin.
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The second patient was an 88-year-old male who had been on dialysis. He was also diagnosed with an acute myocardial infarction associated with cardiogenic shock. At 5.5 h after his arrival, his blood myoglobin and troponin T were 388 µg/L and >2.0 µg/L, respectively. Serum creatine kinase activity was 946.9 µkat/L (5670 U/L). We diluted the sample 2-, 4-, 8-, 16-, and 32-fold with the blood from a healthy individual and reassayed the dilutions as for the first case. The myoglobin concentrations in these diluted samples were >700, 688, 598, 342, and 133 µg/L, respectively (Table 1
, Case B). The myoglobin in a serum sample that had been drawn simultaneously was 
8000 µg/L, as measured on the Elecsys 2010 (Roche Diagnostics). The myoglobin concentration was underestimated in this case as well.
Because there have been no reports of the hook effect for myoglobin on the Cardiac Reader system, we evaluated whether falsely low concentrations below the cutoff would be obtained by preparing blood samples with very high myoglobin concentrations. The myoglobin concentration in a heparin-treated blood sample drawn from a healthy person was <30 µg/L with Cardiac Reader. Myoglobin from human heart (Sigma) was added to the heparinized whole blood to give three specimens with adjusted theoretical concentrations of 115 000, 57 500, and 28 750 µg/L. We used two different Cardiac Readers. Instrument A gave values of 435, >700, and >700 µg/L, whereas instrument B gave values of 526, 617, and >700 µg/L, respectively (Table 1
). Because the results of the dilution tests in the two cases and in the blood containing the added myoglobin were not coincident with each other, we could not determine the myoglobin concentration at which the hook effect occurs. The reason for this discrepancy is not clear, but one possibility is that it is caused by differences in the antigenicity of the myoglobin in the samples.
Although the hook effect is a common problem in immunoassays, it is observed less frequently in assays using immunochromatography. As with the Cardiac Reader, there have been no reports regarding the frequency of a hook effect. We did not observe falsely low values below the cutoff (80 µg/L) in our studies. Other cardiac markers, such as creatine kinase, are probably abnormally high in most cases in which the hook effect of myoglobin occurs; therefore, the risk of making a misdiagnosis is probably limited. However, because blood myoglobin concentrations can become highly increased in some patients, falsely low results below the cutoff are possible with this method, although this was not the case in our study.
In conclusion, users of the Cardiac Reader should recognize the possibility of a high-dose hook effect in the myoglobin assay.
References
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