A diagnostic dilemma from a presentation of shortness of breath and chest pain

A focused report by: Matthew Nichols, Candice K. Silversides, Anna Woo, Felix Leung, Jennifer Taher, Qianghua Zhou and Davor Brinc.

Introduction: A patient presented to hospital with chest pain and shortness of breath on 2 occasions 4 weeks apart. Clinical examination revealed an elevated jugular venous pressure consistent with heart failure or elevated filling pressures.

Methods: The patient was investigated through various modalities including electrocardiogram (ECG), transtho-racic echocardiogram, coronary angiography, MRI, cardiac catheterization, positron emission tomography, and an extensive laboratory workup.

Results: Serial hs TnI measurements consistently revealed grossly elevated troponin I (>10 000 ng/L). In-lab investigation of increased high sensitivity troponin I (hsTnI) showed evidence of falsely increased troponin due to the presence of heterophilic antibodies.

Discussion: This case demonstrates a complex patient presentation and the value of involving the laboratory medicine team when dealing with potentially discrepant results. This is a rare report of grossly elevated troponin due to heterophilic antibodies for high-sensitivity troponin Abbott assay.

IMPACT STATEMENT

This report demonstrates a grossly elevated high-sensitivity troponin (>10 000 ng/L) primarily due to the presence of a heterophilic antibody. Notably, the sample diluted linearly which questions the utility of dilu-tion as an initial screen for heterophiles. This level of falsely elevated troponin is much higher than most heterophilic interferences that have been reported for high-sensitivity troponin I.

Read the full report, highlighting the value of involving the lab on discrepant results.

Dr. Davor Brinc, Clinical Biochemist breaks down the importance of this report

One of the most important tests that cardiology does from a lab perspective is to detect troponin levels.

Cardiac troponin I and troponin T are biomarkers of cardiac injury and are measured to detect if there is damage to the heart muscle.

“Troponins in a blood sample are typically measured by immunoassays; these types of assays use antibodies (typically derived from animal species) to capture troponin and generate a signal which is converted to a concentration. At UHN, we measure cardiac troponin I. Immunassays can have interferences, one of them is macro-troponin: troponin combines with an anti-troponin antibody that rarely may be present in blood and creates a falsely elevated signal,” he says. “The other type is a heterophillic antibody, this is an antibody a person may have which happens to cross react with some of the animal antibodies within the reagent used to detect troponin.”

These will actually bind the reagent antibody and create a false signal.

“What’s special about this case is that the level of signal that we saw was extremely high – we were reporting troponin I of >10 000 ng/L. Normally you shouldn’t have more than 16 (female) or 26 (male) ng/L. And, typically when we see a false positive, the levels will not be that elevated, although the exact frequency and the level of false positive results is not well established,” he says.

After bringing the patient back in for some testing, the cardiology team contacted the lab for help.

The lab team was able to investigate what might be the cause of this elevation using a standard set of methods and determined that this was a false positive result.

“The patient had antibodies, which happened to cross react with our reagent creating this enormously false-positive signal which has never been reported before in such a high level for the current generation of troponin immunoassays,” says Brinc.

He stresses the significance of a thorough investigation and collaboration within UHN laboratories when interference is suspected.

“It’s important to encourage collaboration between any clinical unit and the lab,” says Brinc. “Especially when the result doesn’t really fit the clinical picture that well. It pays off to contact the lab – we are happy to help work out any discrepancy.”

Working together can help to avoid diagnostic uncertainty and reach a conclusion sooner – which is beneficial for patients and clinicians.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

Create a free website or blog at WordPress.com.

Up ↑

%d bloggers like this: