Using the hemoglobin-binding Staphylococcus aureus protein IsdH to enable plasma analysis of hemolyzed blood samples.

Background Intravascular hemolysis and in vitro hemolysis are prevalent contributors to failed blood sample analysis in the routine hospital laboratory. Interferences by hemoglobin in spectrophotometric and certain enzyme activity assays is the major causative factor. Methods By exploiting the hemoglobin-binding properties of the iron-regulated surface determinant H (IsdH) protein from Staphylococcus aureus we have developed a new method to instantly remove hemoglobin and hemoglobin-haptoglobin complexes from plasma in vitro thereby enabling the measurement of hemoglobin-sensitive analytes in hemolyzed plasma. In the present study we used an engineered IsdH mutant form conjugated to Sepharose for the efficient removal of plasma hemoglobin in concentrations up to 15 mg/mL. The high abundance of haptoglobin, which forms a tight complex with hemoglobin in plasma, did not affect the hemoglobin removal by IsdH Sepharose. Results Applying the method on plasma samples that beforehand were spiked with blood hemolysate re-enabled measurement of the hemolysis sensitive parameters: alkaline phosphatase, conjugated bilirubin, iron, ferritin, γ-glutamyltransferase, total thyroxine and troponin T. IsdH Sepharose-mediated hemoglobin removal also enabled measurement of hemolysis sensitive parameters in hemolyzed samples from anonymized patients. Conclusions In conclusion, IsdH Sepharose is a simple cost-effective pretreatment of hemolyzed samples correcting and enabling the measurement of several important hemoglobin-sensitive parameters in a way compatible with standard procedures in routine laboratories.

Can High-Sensitivity Troponins Predict Future Hypertension? A Systematic Literature Review.

Hypertension (HT) is associated with cardiovascular events and increased mortality, and identification of persons at risk in due time is therefore important. Finding a biomarker to identify those at risk will enable early preventive treatment, and high-sensitivity cardiac troponin (hs-cTn) seems to be a highly relevant candidate. To gather the existing knowledge on the association between hs-cTn and future HT, a systematic literature review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guidelines and using the PICOS system. Medline was searched until August 2018. Of 45 extracted papers, eleven papers were eligible for the study. None were randomized controlled trials. Three studies assessed hs-cTnI, eight studies assessed hs-cTnT. All studies found statistically significant associations between hs-cTn concentrations and future HT, but the studies included different types of blood pressure (diastolic, systolic, diurnal). Due to differences in troponin assay construction and test capability, a direct comparison of test performance in terms of specificity, sensitivity and predictive values was not possible, and a specific hs-cTn cutoff value for HT prediction could therefore not be defined. Furthermore, a number of conditions known to affect troponin concentrations (e.g. gender, renal function, and co-morbidities) were not sufficiently studied. All retrieved studies found significant associations between hs-cTn concentrations and future HT; although the findings are promising, the studies were too heterogeneous, and many conditions affecting troponin concentrations needs investigation at these low concentrations before hs-cTn can be considered a useful HT predictor.

The microINR portable coagulometer: analytical quality and user-friendliness of a PT (INR) point-of-care instrument.

Regular measurement of prothrombin time as an international normalized ratio PT (INR) is mandatory for optimal and safe use of warfarin. Scandinavian evaluation of laboratory equipment for primary health care (SKUP) evaluated the microINR portable coagulometer (microINR®) (iLine Microsystems S.L., Spain) for measurement of PT (INR). Analytical quality and user-friendliness were evaluated under optimal conditions at an accredited hospital laboratory and at two primary health care centres (PHCCs). Patients were recruited at the outpatient clinic of the Laboratory of Medical Biochemistry, St Olav's University Hospital, Trondheim, Norway (n = 98) and from two PHCCs (n = 88). Venous blood samples were analyzed under optimal conditions on the STA-R®Evolution with STA-SPA + reagent (Stago, France) (Owren method), and the results were compared to capillary measurements on the microINR®. The imprecision of the microINR® was 6% (90% CI: 5.3-7.0%) and 6.3% (90% CI: 5.1-8.3) in the outpatient clinic and PHCC2, respectively for INR ≥2.5. The microINR® did not meet the SKUP quality requirement for imprecision ≤5.0%. For INR <2.5 at PHCC2 and at both levels in PHCC1, CV% was ≤5.0. The accuracy fulfilled the SKUP quality goal in both outpatient clinic and PHCCs. User-friendliness of the operation manual was rated as intermediate, defined by SKUP as neutral ratings assessed as neither good nor bad. Operation facilities was rated unsatisfactory, and time factors satisfactory. In conclusion, quality requirements for imprecision were not met. The SKUP criteria for accuracy was fulfilled both at the hospital and at the PHCCs. The user-friendliness was rated intermediate.

Comparison of plasma total carbon dioxide and standard hydrogen carbonate in a hospital laboratory setting.

BACKGROUND: Studies comparing venous total carbon dioxide (tCO2) and standard hydrogen carbonate (HCO3-(P,st)) has shown diverse results, and it is debatable whether these two parameters can be used interchangeably for workup of acid-base disorders in a hospital setting. METHOD: All patients with an HCO3-(P,st) requisition from any department at Odense University Hospital between 11th May 2021 and 1st June 2021 had tCO2 and HCO3-(P,st) analysed simultaneously. TCO2 was measured on Cobas® 8000, c702 module, while HCO3-(P,st) was calculated based on measurements on ABL835 Flex. RESULTS: From 1210 patients, mean (standard deviation (SD)) was 22.9 (3.7) mmol/L for tCO2 and 22.5 (2.9) mmol/L for HCO3-(P,st). TCO2 range was 10.1-42.3 mmol/L and 11.7-41.4 mmol/L for HCO3-(P,st). Linear regression showed that tCO2 (mmol/L) = -2.90 + 1.15 × HCO3-(P,st) (mmol/L) with R2 = 0.81. Bias (mean (SD) difference) between tCO2 and HCO3-(P,st)) was 0.4 (1.7) mmol/L with a -5.0-9.6 mmol/L range. Limits of agreement was -2.90-3.70 mmol/L. Comparison of classification within, above or below reference interval for tCO2 and HCO3-(P,st) showed that 984 samples (81%) retained their classification. Only one sample (0.1%) would be severely misclassified (outside the respective reference intervals) if HCO3-(P,st) was considered the gold standard. Of the samples investigated, 46.1% had a mean difference between tCO2 and HCO3-(P,st) of 0-1 mmol/L and 30.3% had 1.1-2.0 mmol/L. CONCLUSIONS: Our results indicate that venous tCO2 and venous HCO3-(P,st) can be used interchangeably in a hospital setting for workup of acid-base disorders.

Pseudohyponatraemia caused by acute pancreatitis-derived hypertriglyceridaemia.

We report a case of pseudohyponatraemia due to severe hypertriglyceridaemia-induced acute pancreatitis, stemming from unknown diabetes. A woman in her late 30s was admitted to the local hospital by her general practitioner due to severe hyponatraemia (116 mmol/L) and upper abdominal pain. At admission to the hospital, there was a discrepancy of 19 mmol/L between arterial and venous sodium, along with severe hypertriglyceridaemia and hypercholesterolaemia. Pancreatitis was diagnosed using a CT scan. The patient received plasmapheresis which significantly reduced triglycerides, and venous plasma sodium was normalised indicating pseudohyponatraemia at admission. Finally, a haemoglobin A1c of 83 mmol/mol was found. Diabetes was diagnosed, and insulin was initiated.

[Rapid and secure exclusion of myocardial infarctionwithout ST-segment elevation].

Rapid identification of acute myocardial infarction (MI) is important for the early initiation of evidence-based therapy. In the European Society of Cardiology (ESC) 0/1h-algorithm (also called early-rule-out algorithm) high-sentivity cardiac troponin is measured at admission and one hour later. By using assay-specific cut-off levels patients are triaged to three different groups; "rule-out", "observation" or "rule-in" of acute MI. The ESC 0/1h-algorithm has high diagnostic accuracy and safety to rule out MI. This review summaries the current knowledge and practical use of the new early-rule-out algorithm.

Plasma viscosity: Evaluation of a new measuring method using microfluidic chip technology (microVisc™) for clinical use and determination of a new reference range.

BACKGROUND: Plasma viscosity is an important biomarker both in diagnostics and treatment monitoring of plasma cell dyscrasias and other disorders with hyperviscosity syndrome as a clinical manifestation. Here, we investigate the performance of a new microfluidic-based viscometer for clinical use, establish a new reference range to be used with this instrument and determine the importance of sampling temperature. METHODS: The microVisc™ viscometer was evaluated for within-run and between-run imprecision and bias using standardized reference material (Paragon controls) and Seronorm™ control material. The reference range was established for the adult population using EDTA-plasma from 120 healthy blood donors. Sampling temperature was investigated by drawing and transporting blood at room temperature and 37°C and comparing the viscosity between the two sampling methods. RESULTS: The microfluidic-based viscometer performed well, and imprecision was comparable to ReoRox® G2 free oscillation rheometer. A new reference range for the adult Danish population was established as 1.2-1.5 mPa s at 37°C. Furthermore, sampling temperature at room temperature and 37°C was investigated, and there was no difference in results obtained. CONCLUSIONS: MicroVisc™ is suitable for measuring plasma viscosity in a clinical setting and results can be evaluated using the established reference range. Blood sampling for viscosity analysis can be performed as a standard procedure at room temperature.

Stability of direct oral anticoagulants in whole blood and plasma from patients in steady state treatment.

Using functional haemostasis assays, we demonstrated important differences in stability of direct oral anticoagulants (DOACs) in citrated whole blood and plasma from DOAC treated patients. Laboratories and clinicians should take this into consideration and adjust clinical practices accordingly.