Interference from immunocomplexes on a high-sensitivity cardiac troponin T immunoassay

A 39-year-old female Moroccan patient was admitted to the University Hospital of Verona in July 2017 for onset of non-specific chest pain. The local diagnostic protocol for patients with suspected acute coronary syndrome (ACS) encompasses serial assessment of cardiac troponin T (cTnT) with a high-sensitivity (HS) immunoassay on a Roche Cobas 8000 (Roche Diagnostics, Basel, Switzerland; 99th percentile value, 14 ng/L), as currently recommended by the fourth universal definition of myocardial infarction [1]. The initial concentration of HS-cTnT was considerably high (i.e. 1114 ng/L), and always remained over the diagnostic threshold in the narrow following period (i.e. after 3 and 6 h from admission). During the following inhospital stay, serial ECGs and repeated measurement of HS-cTnT were carried out. The results of chest computed tomography angiography (CTA), echocardiography, exercise ECG stress testing and cardiac magnetic resonance imaging (MRI) [1], allowed ruling out any potential cause of myocardial injury. The patient had a positive clinical history for chronic kidney disease, which developed after an idiopathic membranous glomerulonephritis, thrombophilia complicated by an episode of pulmonary embolism (PE) secondary to right renal vein and inferior vena cava thrombosis, depressive-anxiety syndrome, endometriosis, two previous miscarriages and recurrent migraine. Nearly 29 months later (on December 21, 2019), the patient was readmitted to the Emergency Department of the University Hospital of Verona, reporting epigastric pain with retrosternal irradiation up to the jugular, exacerbated by deep inspiration and supine decubitus, described as burning, mostly nocturnal. Hence, an ACS was suspected and a blood sample was immediately drawn. The concentration of HS-cTnT was still considerably increased (i.e. 1132 ng/L), whilst ECG and echocardiography – performed immediately afterwards – did not reveal abnormal findings. Physical examination did not reveal any abnormality of cardio-pulmonary objectivity, except for a mild hypertension. The patient remained afebrile throughout hospitalization. Nevertheless, due to persistently elevated HS-cTnT concentrations measured throughout nine consecutive days of hospitalization (i.e. 1132, 981, 849, 983, 1020, 1051, 1116, 1049 and 1025 ng/L), additional specific tests were ordered, i.e. myoglobin, 37 μg/L; total creatine kinase (CK), 28 U/L and CK-MB, <1 μg/L. A broad immunological panel, including autoantibodies (such as anticardiolipin and anti-beta 2 glycoprotein), antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA) and extractable nuclear antigen antibodies (ENA) did not display marked abnormalities, except for mild ANA positivity (1:160; homogenous pattern). No pathological findings could also be detected with repeated ECG and echocardiography. The patient was managed with an intravenous proton pump inhibitor (PPI), anticoagulant therapy and intravenous supplementation with crystalloids. Notably, chest pain regressed after administration of PPI, so that the patient underwent esophagus-gastric endoscopy, which allowed the diagnosis of a mild chronic gastritis. *Corresponding author: Luca Dalle Carbonare, MD, PhD, Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy, Phone: +390458124262, Fax: +390458027496, E-mail: luca.dallecarbonare@univr.it. https://orcid.org/0000-0003-3263-6671 Michela Pizzini, Valentina Micheletti and Domenico Girelli: Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy Claudia Lo Cascio: Service of Laboratory Medicine, University Hospital of Verona, Verona, Italy Chiara Bovo: Medical Direction, University Hospital of Verona, Verona, Italy Giuseppe Lippi: Service of Laboratory Medicine, University Hospital of Verona, Verona, Italy; and Section of Clinical Biochemistry, University of Verona, Verona, Italy Clin Chem Lab Med 2020; 58(10): e225–e227