Circulating forms of cardiac troponin:a review with implications for clinical practice

Cardiac troponin I (cTnI) and T (cTnT) became the gold-standard biomarkers for diagnosing myocardial infarction (MI) due to their cardiac-specific amino acid sequence. Currently, both cTnI and cTnT are considered equivalent as their diagnostic performance is comparable. The introduction of highsensitivity (hs-)cTn immunoassays allowed a more accurate assessment of cTn concentrations in the lower analytical range resulting in a higher number of non-ST-elevated MI (NSTEMI) diagnoses. However, the increased sensitivity also resulted in hs-cTn elevations in other (non-)cardiac pathologies and even in physiological conditions, such as vigorous exercise. To differentiate acute MI from these other conditions it was suggested that the circulating form of cTn might serve useful, since research illustrated different circulating cTnI and cTnT forms in the blood circulation. Studies in acute MI patients have shown that cTnI appears to be mostly present in a binary (cTnI-C) complex. Also, a variety of different cTnI fragments was observed post-MI, but no time-dependent cTnI degradation effect was found dependent on symptom onset. For cTnT, mainly larger forms were found in MI, while in other conditions with elevated hs-cTnT concentrations, the smallest fragments were almost exclusively present. Based on this preliminary data it might be clinically relevant to develop a novel hs-cTnT immunoassay which solely targets specific cTnT forms observed in acute MI that could help to further increase the specificity of hs-cTnT immunoassay for the diagnosis of acute MI. The present traditional literature review provides an overview of research on circulating cTn forms performed thus far

“Macro transcobalamin causing raised vitamin B12: Case-based laboratory investigation"

Determination of plasma vitamin B12 (B12) is a frequently requested laboratory analysis, mainly employed to establish B12 deficiency. However, an increased level of B12 is a common unexpected finding that may be related to an increased concentration of one of the B12 binding proteins, haptocorrin or transcobalamin. This paper describes the extensive laboratory evaluation of a patient with an elevated level of plasma B12 with various well-established assays. Initial studies suggested the presence of a macromolecule consisting of haptocorrin bound B12. Specific determinations of the B12-binding proteins revealed normal amounts of haptocorrin but a markedly increase in both total and B12 saturated transcobalamin (holo-TC). The results are in accord with the presence of macro-transcobalamin. These experiments reveal that determination of the nature of the B12-macromolecules is troublesome due to differences in assays applied to measure these proteins. In addition, this publication creates awareness of macro-holo-TC as a cause of an unexplained increased B12 level