Band 52, Heft 6

In our hospital, we are currently working to manage the appropriateness of vitamin B 12 (B12) testing. Unfortunately, the classic evidence-based approach is unhelpful in this process and meta-analyzing data on the accuracy of this marker for cobalamin deficiency detection is misleading due to the lack of reference diagnostic methods. The approach currently proposed by the Health Technology Assessment (HTA) enables us to tackle the issue of B12 requests as a “healthcare” problem by considering the position of stakeholders involved in ordering, performing, interpreting the test, and receiving its results. Clinical expectations, methodological issues, and ethical aspects concerning the performance of the test can aid us in providing more guidance on the use of this marker. By building such structured information, hemodialysis patients and pregnant women have emerged as those groups preferentially requiring B12 testing, as it may potentially improve the clinical outcome. To avoid misinterpretation of B12 results more care should be taken in considering its biochemical and biological features, as well as the analytical issues. Spurious values obtained by current automated immunoassays may reflect suboptimal pre-analytical steps as well as known interfering conditions. Furthermore, the harmonization of results by available methods is still a far-reaching goal and the approach to interpret an individual’s results should be improved. Tracing a roadmap for B12 testing by exploiting the HTA model to balance the stakeholders’ claims and maximizing the patient’s outcome may help to manage the marker demand.

The aim of this work was to assess the diagnostic value of anti-CCP-3 and anti-CCP-2 for the diagnosis of rheumatoid arthritis (RA) and determine whether anti-CCP-3 more accurately identifies patients with rheumatoid arthritis than anti-CCP-2. PubMed and CNKI databases were searched for studies published in English and Chinese that examined the use of anti-CCP-3 and anti-CCP-2 in the diagnosis of known or suspected rheumatoid arthritis from January 2006 to July 2013. Seventeen included studies of methodological quality were rated by using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tools A random-effects method was used to summarize sensitivities, specificities, positive and negative likelihood ratio (LR+ and LR−, respectively), and diagnostic odds ratio from 17 studies. The pooled sensitivity, specificity, LR+, LR− and diagnostic odds ratio for anti-CCP-3 were 0.737 (95% CI, 0.717–0.757), 0.933 (95% CI, 0.924–0.942), 11.096 (95% CI, 8.876–13.870), 0.274 (95% CI, 0.231–0.326), and 42.908 (95% CI, 33.828–54.426), respectively. For anti-CCP-2, the values were 0.719 (95% CI, 0.699–0.739), 0.960 (95% CI, 0.953–0.966), 17.485 (95% CI, 11.960–25.562), 0.294 (95% CI, 0.258–0.335) and 63.458 (95% CI, 44.214–91.078), respectively. With high specificity and moderate sensitivity, anti-CCP-2 and anti-CCP-3 played an important role in confirming the diagnosis of RA. Anti-CCP-3 did not have better diagnostic performances than anti-CCP-2, but anti-CCP-2 had evident heterogeneity compared to anti-CCP-3, especially in American patients.

The cancer biomarker field appears to be stagnant. Very few, if any, new cancer biomarkers have been introduced into clinical practice the last 20 years. The reason is that most of the newly discovered cancer biomarkers are inferior in terms of sensitivity and specificity to the classical cancer biomarkers that we currently use. The revolutionary technologies of proteomics, genomics, and other omics did not deliver on the promise to discover new and improved cancer biomarkers. However, more recently, the explosive growth of whole genome and exome sequencing has provided for the first time nearly complete mutational landscapes of many cancer types, in thousands of samples. We now know that many of these mutations are only found in cancer. It is thus possible that the mutant proteins encoded by these genes may represent the long-sought, highly specific cancer molecules that we may envision to use as cancer biomarkers. I here speculate that modern mass spectrometry may have the necessary sensitivity and specificity to detect mutant proteins in various biological fluids for the purpose of diagnosis, prognosis, and disease monitoring.

In 2013, the National Cancer Institute of the USA announced a new program, to catalog “exceptional responders” in cancer trials. This program aims to identify a small number of well-responding patients to new treatments, with the hope that in the future, patients with cancer could be treated with the most effective drugs (personalized therapy). In this paper, I extrapolate on this idea and propose to also catalog cancer biomarkers that only work in a minor proportion of patients, and are currently ignored as clinically useless. Such biomarkers could be used to select optimal treatments, optimal monitoring or for assessing prognosis. The informative biomarkers for these rare patients may also provide the opportunity to identify molecular networks that are altered in cancer and explain why these markers are elevated in these few patients. I provide an example of two kallikreins (KLK6 and KLK10), which are highly elevated in serum of 3%–5% of pancreatic cancer patients at 100% specificity.

Background: CYP2D6, a major drug-metabolizing enzyme, is encoded by a highly polymorphic and complex gene locus. We have identified a patient who failed to produce a CYP2D6 genotype with the AmpliChip P450 Test ® (AmpliChip), whereas his CYP2C19 genotype was readily determined. The aim of this investigation was to fully characterize the patient’s CYP2D6 gene locus to resolve the AmpliChip no-call. Methods: The case, a brother, and son were genotyped with the AmpliChip and subsequently characterized using long-range (XL)-PCR coupled with TaqMan assay technology. Copy number variation was assessed by XL-PCR and quantitative PCR. Selected XL-PCR products were sequenced. Results: The AmpliChip also produced a no-call for the son; the brother produced a result. The two alleles of the case were subsequently found to carry additional gene units that likely caused the AmpliChip no-calls. One was characterized as a CYP2D6*68+*4 tandem ( CYP2D6*68 is a hybrid gene composed of 2D6 and 2D7 ), the other as a rare CYP2D6*13+*2 tandem ( CYP2D6*13 is a 2D7/2D6 hybrid formerly known as CYP2D6*77 ). A novel CYP2D6*2 subvariant was identified in the son; the brother also carried the CYP2D6*68+*4 tandem. Conclusions: The implementation of pharmacogenetics-guided drug therapy relies on accurate clinical-grade genotype analysis. Although the AmpliChip is deemed to be a reliable platform, numerous more recently discovered allelic variants and gene arrangements are not detected or trigger no-calls. Although such cases may be rare, the clinical/genetic testing community must be aware of the challenges of CYP2D6 testing on the AmpliChip platform and implications regarding accuracy of test results.

Background: Allowable analytic errors are generally based on biologic variation in normal, healthy subjects. Some analytes like blood lactate have low concentrations in healthy individuals and resultant allowable variation is large when expressed as a coefficient of variation (CV). In Ricós’ compendium of biologic variation, the relative pooled intra-individual lactate variation (s i ) averages 27% and the desirable imprecision becomes 13.5%. We derived biologic variability (s b ) from consecutive patient data and demonstrate that s b of lactate is significantly lower. Methods: A data repository provided lactate results measured over 18 months in the General Systems intensive care unit (ICU) at the University of Alberta Hospital in Edmonton, Canada. In total 54,000 lactate measurements were made on two point-of-care Radiometer 800 blood gas systems operated by Respiratory Therapy. The standard deviations of duplicates (SDD) were tabulated for the intra-patient lactates that were separated by 0–1, 1–2…up to 16 h. The graphs of SDD vs. time interval were approximately linear; the y-intercept provided by the linear regression represents the sum of s b and short-term analytic variation (sa):y0=(sa2+s)b212.\(({{\rm{s}}_{\rm{a}}}):{{\rm{y}}_{\rm{0}}} = {({\rm{s}}_{\rm{a}}^{\rm{2}} + {\rm{s}}{}_{\rm{b}}^{\rm{2}})^{{1 \over 2}}}.\) The short-term s a was determined from imprecisions provided by Radiometer and confirmed with onsite controls. The derivation of s b was performed for multiple patient ranges of lactate. Results: The relative desirable lactate imprecision for patients with lactic acidosis is about half that of normal individuals. Conclusions: As such, evaluations of lactate measurements must use tighter allowable error limits.

Background: The performance of creatinine-based glomerular filtration rate (GFR) estimating equations may vary in subgroups defined by GFR, age and body mass index (BMI). This study compares the performance of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with the revised Lund-Malmö equation (LM Revised), a new equation that can be expected to handle changes in GFR across the life span more accurately. Methods: The study included 3495 examinations in 2847 adult Swedish patients referred for measurement of GFR (mGFR) 2008–2010 by plasma clearance of iohexol (median 52 mL/min/1.73 m 2 ). Bias, precision [interquartile range (IQR)] and accuracy [percentage of estimates ±10% (P 10 ) and ±30% (P 30 ) of mGFR] were compared. Results: The overall results of LM Revised/MDRD/CKD-EPI were: median bias 2%/8%/11%, IQR 12/14/14 mL/min/1.73 m 2 , P 10 40%/35%/35% and P 30 84%/75%/76%. LM Revised was the most stable equation in terms of bias, precision and accuracy across mGFR, age and BMI intervals irrespective of gender. MDRD and CKD-EPI overestimated mGFR in patients with decreased kidney function, young adults and elderly. All three equations overestimated mGFR and had low accuracy in patients with BMI <20 kg/m 2 , most pronounced among men. Conclusions: In settings similar to the investigated cohort LM Revised should be preferred to MDRD and CKD-EPI due to its higher accuracy and more stable performance across GFR, age and BMI intervals.

Background: Although fetal blood sampling for pH is well established the use of lactate has not been widely adopted. This study validated the performance and utility of a handheld point-of-care (POC) lactate device in comparison with the lactate and pH values obtained by the ABL 800 blood gas analyzer. Methods: The clinical performance and influences on accuracy and decision-making criteria were assessed with freshly taken fetal blood scalp samples (n=57) and umbilical cord samples (n=310). Bland-Altman plot was used for data plotting and analyzing the agreement between the two measurement devices and correlation coefficients (R 2 ) were determined using Passing‐Bablok regression analysis. Results: Sample processing errors were much lower in the testing device (22.8% vs. 0.5%). Following a preclinical assessment and calibration offset alignment (0.5 mmol/L) the test POC device showed good correlation with the reference method for lactate FBS (R 2 =0.977, p<0.0001, 95% CI 0.9 59–0.988), arterial cord blood (R 2 =0.976, p<0.0001, 95% CI 0.967–0.983) and venous cord blood (R 2 =0.977, p<0.0001, 95% CI 0.968–0.984). Conclusions: A POC device which allows for a calibration adjustment to be made following preclinical testing can provide results that will correlate closely to an incumbent lactate method such as a blood gas analyzer. The use of a POC lactate device can address the impracticality and reality of pH sample collection and testing failures experienced in day to day clinical practice. For the StatStrip Lactate meter we suggest using a lactate cut-off of 5.1 mmol/L for predicting fetal acidosis (pH<7.20).

Background: In recent years, several selectively acting anticoagulants, including the direct thrombin inhibitors (DTI; argatroban, dabigatran) and the factor Xa inhibitors (rivaroxaban, apixaban, fondaparinux), have been developed. With their clinical application increasing, it is of interest to evaluate their interference with classical haemostaseological point-of-care tests. Additionally, the effect of the investigated anticoagulants on platelet function tests will come increasingly more into focus for monitoring not only hereditary platelet dysfunction, but also antiplatelet therapy. Methods: Blood samples from healthy volunteers were spiked with therapeutic and supratherapeutic concentrations of the drugs listed above and investigated with regard to their effects on the following POCTs: activated clotting time (ACT), thromboelastometry with ROTEM ® , PFA ® and Multiplate ® . Light-transmission aggregometry (LTA) was used for a platelet function assay. Results: At supratherapeutic concentrations, ACT and ROTEM ® analysis were always influenced after administration of the drugs listed above (except fondaparinux in EXTEM-CT). Therapeutic concentrations showed differential effects on these assays. LTA measurements revealed a distinct decrease in α-thrombin-induced platelet aggregation for both DTIs (therapeutic and supratherapeutic concentrations), while argatroban reduced platelet function in supratherapeutic concentrations. None of the drugs seemed to have any influence on PFA ® or Multiplate ® . Conclusions: Selective thrombin and factor Xa inhibitors exhibit distinct effects on POCTs and platelet function tests. This must be considered in assessing assay results when taking medical decisions.

Background: The few available External Quality Assessment (EQA) programs on urinary sediment rarely include an evaluation of clinical cases. The present paper provides a descriptive analysis of clinical cases included in the Italian EQA program on urinary sediment. Methods: Ten cases were presented over a 5-year period (2007–2011). Each clinical case included a brief clinical history, some key laboratory data and four key urinary sediment particles obtained by phase contrast microscopy. The clinical diagnoses indicated by participants, chosen among four or five proposed, were evaluated only for those who had been able to correctly identify all four urinary sediment particles. The results of each survey were then evaluated, scored and commented on. Results: The numbers of participants for the 10 surveys ranged from 268 to 325. Throughout surveys, only 63.9%±17.0% (range 39.6%–88.7%) of participants achieved access to clinical diagnosis. Of these, 90.2%±8.5% (range 73.7%–98.1%) were able to indicate the correct diagnosis. Conclusions: Our findings demonstrate that once the correct identification of urinary sediment particles is obtained, most participants are able to associate urinary findings with the respective clinical conditions, thus establishing the correct diagnosis.

Background: The aim of this study was to establish ranges for N Latex free light-chain (FLC) monoclonal-based nephelometric assays in patients with renal impairment. Methods: In this retrospective study, serum samples from 284 patients with chronic kidney disease (CKD) stages 1–5 were measured with N Latex and Freelite™ FLC reagents on the Siemens BN™II system and compared with controls without renal impairment. Results: Both κFLC and λFLC concentrations increased with the N Latex FLC and the Freelite™ assays with each increment in CKD stage. No difference was found in FLC κ concentrations between the two methods. In patients with renal failure, N Latex FLC detected higher concentrations of λFLC (CKD5 median, 128 mg/L; 95% range, 43–302) compared with Freelite™ (89.5 mg/L, 35–197) (p<0.0001). This resulted in significantly different κ/λ ratios in patients with CKD for the two tests. The Freelite™ κ/λ ratio in the CKD5 group (median, 1.22; min–max, 0.22–2.70) was significantly increased compared with healthy controls (p<0.0001), and several individual samples were outside the reference range for healthy controls (0.26–1.65). In contrast, none of the 284 patients with CKD had an FLC κ/λ ratio exceeding the N Latex reference limits for healthy controls (0.31–1.56). The N Latex FLC κ/λ ratio in the CKD5 group (0.69, 0.32–1.54) was significantly lower compared with the control group (p<0.0001). Conclusions: These findings demonstrate that the N Latex FLC κ/λ ratio in patients with renal failure did not differ from the reference limits for healthy controls.

Background: The measurement of C-reactive protein (CRP) concentrations has been of interest as a classical marker of acute phase response; in addition, it has been of particular interest in cardiovascular risk stratification where high-sensitive measurements are necessary. Since CRP is able to bind phospholipids (mainly phosphocholine) in the presence of calcium ions, we explored the possibilities of developing a high-sensitive affordable nephelometric CRP assay based on diluted soy oil emulsions. Methods: Serum (or heparinized plasma) was mixed with Intralipid 20% in Tris-calcium buffer (pH 7.5). After 12 min of incubation at 37°C, the CRP-phospholipid complexes were measured by nephelometry (840 nm) using a BN II nephelometer (Siemens). Results (n=97) were compared with those obtained using a typical immunoturbidimetric method (Roche). Results: Imprecision of the functional nephelometric assay was evaluated using three human serum pools. Within-run coefficients of variation (CVs) for level 1, 2 and 3 were 6.1%, 4.7% and 4.5%, respectively, and between-run CVs were 17.6%, 18.8% and 11.3%, respectively. Good agreement was obtained between the functional nephelometric and the immunoturbidimetric CRP assay in a concentration range from 0.1 mg/L to 50 mg/L (r=0.884). A logit-log calibration curve was made between 0.056 mg/L and 1.785 mg/L. The limit of detection was 0.5 mg/L. Conclusions: The functional nephelometric CRP assay allowed high-sensitive CRP determinations in serum and plasma. Since the assay is species independent, the described functional CRP assay could be used for veterinary purposes as well.

Background: Oxidized lipoprotein(a) [ox-Lp(a)] and oxidized low density lipoprotein (ox-LDL) levels have been reported to be useful predictors of cardiovascular events. The study developed a chemiluminescence (CL) imaging immunoassay method for simultaneously detecting serum concentrations of ox-Lp(a) and ox-LDL. Methods: Ox-Lp(a) and ox-LDL levels were measured by CL imaging immunoassay using a disposable immunosensor array as the carrier and a charge-coupled device as the detector, and were studied in 46 acute coronary syndromes (ACS) patients, 58 stable coronary artery disease (CAD) and 61 control subjects. Results: This method showed good linear relations (R 2 >0.99) in the concentration range of 2.00×10 –5 –2.00×10 –1 and 2.40×10 –4 –2.40 U/mL for ox-Lp(a) and ox-LDL, respectively. The detection limits for ox-Lp(a) and ox-LDL were 2.40×10 –6 and 3.00×10 –5 U/mL, respectively. The intra- and inter-assay coefficients of variation (CV) were 4.90%–6.76% and 7.11%–10.06% for ox-Lp(a), and 5.01%–6.04% and 5.47%–9.77% for ox-LDL, respectively. The mean recovery was 99.31% for ox-Lp(a) and 99.57% for ox-LDL, respectively. Significant correlations were observed between ox-Lp(a) levels detected by CL imaging immunoassay and ELISA, and between ox-LDL levels detected by the two methods, respectively. Furthermore, ox-Lp(a) and ox-LDL levels increased in stable CAD, and especially in ACS. Conclusions: The CL imaging immunoassay provided a simple, sensitive and reliable method for the simultaneous determination of serum ox-Lp(a) and ox-LDL. The clinical monitoring ox-Lp(a) and ox-LDL levels may possess distinctly clinical value for assessment of CAD risk.

Background: Teicoplanin is a glycopeptide antibiotic used for the treatment of infections caused by Gram-positive bacteria. There is a good correlation between trough levels and clinical outcome, therefore therapeutic drug monitoring is recommended. Here we present a liquid chromatography-mass spectrometry (LC-MS) method with online extraction based on turbulent flow chromatography for the quantification of the five main components of teicoplanin, A2–1, A2–2, A2–3, A2–4, and A2–5. Methods: After online extraction, analytical chromatography was performed on a Hypersil Gold C8 column under acidic conditions. As mass spectrometer, a Q Exactive hybrid instrument was used. Samples were prepared by adding internal standard and subsequent centrifugation. Patient samples (n=125) that had previously been analyzed using a commercially available immunoassay (QMS ® teicoplanin) were re-analyzed by LC-MS. Results: The imprecision was <6.9%, inaccuracy between 99.6% and 109%, for both, within- and between-day analysis. The method was shown to be free of matrix effects in the relevant time ranges and was compared to a commercially available immunoassay, QMS ® teicoplanin from Thermo Fisher Scientific. The LC-MS assay produced comparable results to the QMS ® assay, the correlation coefficient was 0.856 (95% confidence interval 0.800–0.896). LC-MS yielded lower concentrations than the immunoassay as could be demonstrated by the bias of −1.16 mg/L (95% confidence interval −1.90–0.43 mg/L) in the Bland-Altman analysis. Conclusions: This specific, automated, LC-MS assay for teicoplanin is suitable for therapeutic drug monitoring.

Background: Appropriateness of tumor markers (TMs) has been retrospectively studied in limited patients’ series, matching the requests to clinical records. Methods to monitor appropriateness suitable for use on a large scale are required. This study aims to establish and validate an innovative model to estimate appropriateness based on the comparison between the number of TMs requested and the expected requests inferred from epidemiological data. Methods: The number of CA15.3, CA19.9 and CA125 requests theoretically expected according to the epidemiology of malignancies in a known geographic area (2 Italian regions) was compared with the number of TMs actually requested – the surveyed requests projected on a regional scale – during a given time span (1 year). The expected number of requests was calculated comparing TMs recommended by guidelines in different clinical scenarios with the prevalence or incidence figures of the examined diseases (carcinomas of breast, pancreas and biliary tract, ovary and endometrium). Results: Suitability of the model was demonstrated with the analysis of 1,891,070 TM requests surveyed in 66 laboratories from Veneto and Tuscany regions. The percentage difference over the total of expected TMs (delta%) ranged from −6.9% for CA15.3 to +1022.6% for CA19.9 in Veneto and from +35.7% for CA15.3 to +1842.6% for CA19.9 in Tuscany. Conclusions: The presented model was effective in demonstrating higher than expected TM request rates, possibly associated with inappropriate use. Moreover, it can be applied on a large scale survey setting since it circumvents the unavailability of clinical information on test orders.

Background: Hyper-methylation of CpG dinucleotides in the promoter region of inhibitor of cyclin-dependent kinase 4A ( INK4A ) has been reported in 60%–80% of hepatocellular carcinoma (HCC). As INK4A promoter hypermethylation event occurs early in HCC progression, the quantification of INK4A promoter methylation in blood sample may represent a useful biomarker for non-invasive diagnosis and prediction of response to therapy. Methods: We examined INK4A promoter methylation using circulating cell-free DNA (ccfDNA) in a total of 109 serum specimens, including 66 HCC and 43 benign chronic liver diseases. Methylation of the individual seven CpG sites was examined using pyrosequencing. Results: Our results showed that there were significantly higher levels of methylated INK4A in HCC specimens than controls and that the seven CpG sites had different levels of methylation and might exist in different PCR amplicons. The area under receiver operating characteristic (ROC) curve was 0.82, with 65.3% sensitivity and 87.2% specificity at 5% (LOD), 39.0% sensitivity and 96.5% specificity at 7% LOD, and 20.3% sensitivity and 98.8% specificity at 10% LOD, respectively. Conclusions: Our results support additional studies incorporating INK4A methylation testing of ccfDNA to further validate the diagnostic, predictive, and prognostic characteristics of this biomarker in HCC patients. The knowledge of the existence of epi-alleles should help improve assay design to maximize detection.

Background: The in vitro stability of a biomarker can determine whether it should be used in clinical practice where long delays between sampling and assay are common. We measured the in vitro stability of five novel biomarkers that are being evaluated for their diagnostic and/or prognostic utility in patients with heart failure: mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adreno-medullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), C-terminal pro-arginine vasopressin (copeptin) and ultrasensitive procalcitonin (PCT). Methods: Peripheral venous blood samples were obtained from 19 patients with chronic heart failure into four EDTA tubes. The first tubes were centrifuged immediately at 4°C with the other tubes stored at 20°C for 4, 24 or 72 hours (h) before centrifuging. Supernatant plasma was frozen and stored at −80°C until assay. The levels of analyte in samples processed with and without delay were compared using correlation analysis, paired t-tests and Bland-Altman plots. Results: Copeptin and PCT were stable up to 72 h at 20°C in whole blood and MR-proANP and MR-proADM up to 24 h. However, CT-proET-1 showed some signs of degradation after only 4 h with 94% of analyte recovered after 24 h, dropping to 80% after 72 h. Conclusions: MR-proANP, MR-proADM, copeptin and PCT are stable biomarkers and therefore suitable for introduction into routine clinical practice in a primary or secondary care setting where delays in sample preparation and assay are likely. Ideally, samples for measurement of CT-proET-1 should be centrifuged soon after venepuncture but the analyte is stable enough for most routine clinical purposes.

Background: Galectin-3 is secreted from macrophages and binds and activates fibroblasts forming collagen. Tissue fibrosis is central to the progression of chronic heart failure (CHF). We performed a European multicentered evaluation of the analytical performance of the two-step routine and Short Turn-Around-Time ( STAT ) galectin-3 immunoassay on the ARCHITECT i 1000 SR , i 2000 SR , and i 4000 SR (Abbott Laboratories). Methods: We evaluated the assay precision and dilution linearity for both routine and STAT assays and compared serum and plasma, and fresh vs. frozen samples. The reference interval and biological variability were also assessed. Measurable samples were compared between ARCHITECT instruments and between the routine and STAT assays and also to a galectin-3 ELISA (BG Medicine). Results: The total assay coefficient of variation (CV%) was 2.3%–6.2% and 1.7%–7.4% for the routine and STAT assays, respectively. Both assays demonstrated linearity up to 120 ng/mL. Galectin-3 concentrations were higher in plasma samples than in serum samples and correlated well between fresh and frozen samples (R=0.997), between the routine and STAT assays, between the ARCHITECT i 1000 and i 2000 instruments and with the galectin-3 ELISA. The reference interval on 627 apparently healthy individuals (53% male) yielded upper 95th and 97.5th percentiles of 25.2 and 28.4 ng/mL, respectively. Values were significantly lower in subjects younger than 50 years. Conclusions: The galectin-3 routine and STAT assays on the Abbott ARCHITECT instruments demonstrated good analytical performance. Further clinical studies are required to demonstrate the diagnostic and prognostic potential of this novel marker in patients with CHF.

Background: Coagulation abnormalities may have a major impact on the outcome of sepsis in patients. This study aimed to explore the relationship between miRNA levels and coagulation disorders during sepsis. Methods: Blood samples from 123 sepsis patients were collected on the day of admission and another 45 sepsis patients on days 1, 3, 5, 7, 10, and 14 following admission to the intensive care unit. miR-223, miR-15a, miR-16, miR-122, miR-193b*, and miR-483-5p levels were evaluated by quantitative reverse transcription polymerase chain reaction. Based on the International Society on Thrombosis and Haemostasis (ISTH) Disseminated Intravascular Coagulation (DIC) score, sepsis patients were divided into coagulation abnormal (CA) group and coagulation normal (CN) group. Results: Only the levels of miR-122 were significantly higher in CA patients than in CN patients (p<0.001). Serum levels of miR-122 were correlated to the serum activated partial thromboplastin time (APTT) ratios (R=0.426, p=0.008) and the fibrinogen (FIB; R=0.398, p=0.008) and antithrombin III (R=0.913, p<0.001) levels. In addition, Pearson’s correlation coefficients for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with miR-122 were 0.663 (p<0.001) and 0.445 (p=0.001), respectively. In the 45 patients, the miR-122 levels were significantly higher on day 1, 3, 7, and 10 in the CA group than in the CN group, and no difference in the ISTH-DIC scores was evident. Conclusions: Serum levels of miR-122 were correlated to the coagulation disorder in sepsis patients.