Negative interference from immunoglobulin M paraproteinaemia on the Roche enzymatic creatinine method.

Although enzymatic creatinine methods are subject to fewer interferences than traditional Jaffe creatinine methods, every method in clinical chemistry has limitations. We report, for the first time in the literature, a case of an immunoglobulin M (IgM) paraproteinaemia causing an undetectably low creatinine result on the Roche enzymatic assay. This interference did not occur with other enzymatic creatinine methods produced by Abbott and Siemens or the Roche Jaffe, VITROS dry slide and liquid chromatography with tandem mass spectrometry (LC-MS/MS) creatinine methods. IgM interference was confirmed as patient serum precipitated with polyethylene glycol (PEG) and anti-IgM antiserum yielded detectable Roche enzymatic creatinine results comparable to unaffected methods. The patient's serum formed an obvious precipitate when mixed with reagent one of the Roche enzymatic creatinine method. This is in contrast to a report of positive interference from IgM paraproteinaemia in a different enzymatic creatinine method, which showed that a precipitate formed when mixing blood with reagent two. As each patient's paraprotein has a unique structure, it is possible that there are variations in the chemical characteristics of IgM paraproteins between patients. This, as well as IgM-class antibodies' tendency to form multimers and aggregates, can lead to unpredictable assay interferences and precipitation tendencies between different manufacturers of enzymatic creatinine reagents and their incubation steps. This case highlights the importance of continuing to question and investigates results that do not fit the clinical picture, especially as more laboratories switch from primarily using traditional Jaffe creatinine methods to enzymatic creatinine methods.

Cardiac Troponin Release is Associated with Biomarkers of Inflammation and Ventricular Dilatation During Critical Illness.

INTRODUCTION: Troponin release is common during critical illness. We hypothesized that there was an association between cardiac troponin T (cTnT) and biomarkers of systemic inflammation and ventricular dilatation. METHODS: In an observational prospective cohort study, we enrolled consecutive adult patients admitted for noncardiac reasons to the intensive care unit (ICU) in two tertiary care centers. We measured cTnT, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and N-terminal pro brain natriuretic peptide (NT-proBNP) daily in the first week, and on alternate days in the second week. Using a peak cTnT cutoff ≥15 ng/L and concomitant changes on electrocardiogram, patients were categorized as "definite myocardial infarction (MI)," "possible MI," "cTnT rise only," or "no cTnT rise." Within each group, associations between CRP, IL-6, PCT, NT-proBNP, and cTnT were investigated using mixed effect models. RESULTS: One hundred seventy-two patients were included in the analysis of whom 84% had a cTnT rise ≥15 ng/L. Twenty-one patients (12%) had a definite MI, 51 (30%) had a possible MI, and 73 (42%) had a cTnT rise only. At the time of peak cTnT, 71% of patients were septic and 67% were on vasopressors.Multivariable analysis showed a significant association between cTnT and IL-6 in all patients with a cTnT rise independent of age, gender, renal function, and cardiovascular risk factors. In patients without a definite MI, cTnT levels were significantly associated with PCT and NT-proBNP values. In patients without elevated cTnT levels, there was no associated NT-proBNP rise. CONCLUSIONS: In ICU patients admitted for non-cardiac reasons, serial cTnT levels were independently associated with markers of systemic inflammation and NT-proBNP.

Subcutaneous fat necrosis causing neonatal hypercalcaemia.

Hypercalcaemia in neonates is rare and often asymptomatic, but can have significant morbidity. If severe, it can cause symptoms including irritability, vomiting and seizures. We present the case of a baby girl, born at term after a traumatic delivery, who developed severe hypercalcaemia with nephrocalcinosis. She had several large areas of subcutaneous fat necrosis following delivery, with prolonged low-level elevation of C reactive protein. Subcutaneous fat necrosis of the newborn is a rare and underdiagnosed condition, often accompanied by high plasma calcium. Although self-limiting, it is important to recognise and treat this condition to minimise kidney damage, and to avoid unnecessary investigations or treatment with long courses of antibiotics. The infant recovered well, although a degree of nephrocalcinosis remains.

A prospective study of the impact of serial troponin measurements on the diagnosis of myocardial infarction and hospital and six-month mortality in patients admitted to ICU with non-cardiac diagnoses.

INTRODUCTION: Troponin T (cTnT) elevation is common in patients in the Intensive Care Unit (ICU) and associated with morbidity and mortality. Our aim was to determine the epidemiology of raised cTnT levels and contemporaneous electrocardiogram (ECG) changes suggesting myocardial infarction (MI) in ICU patients admitted for non-cardiac reasons. METHODS: cTnT and ECGs were recorded daily during week 1 and on alternate days during week 2 until discharge from ICU or death. ECGs were interpreted independently for the presence of ischaemic changes. Patients were classified into four groups: (i) definite MI (cTnT ≥15 ng/L and contemporaneous changes of MI on ECG), (ii) possible MI (cTnT ≥15 ng/L and contemporaneous ischaemic changes on ECG), (iii) troponin rise alone (cTnT ≥15 ng/L), or (iv) normal. Medical notes were screened independently by two ICU clinicians for evidence that the clinical teams had considered a cardiac event. RESULTS: Data from 144 patients were analysed (42% female; mean age 61.9 (SD 16.9)). A total of 121 patients (84%) had at least one cTnT level ≥15 ng/L. A total of 20 patients (14%) had a definite MI, 27% had a possible MI, 43% had a cTNT rise without contemporaneous ECG changes, and 16% had no cTNT rise. ICU, hospital and 180-day mortality was significantly higher in patients with a definite or possible MI. CONCLUSIONS: The majority of critically ill patients (84%) had a cTnT rise and 41% met criteria for a possible or definite MI of whom only 20% were recognised clinically. Mortality up to 180 days was higher in patients with a cTnT rise.