Analytical validation of 39 clinical chemistry tests and 17 immunoassays on the Alinity analytical system.

The aim of this study was to perform the analytical validation of Alinity c and i analyzers (Abbott Laboratories, Chicago, IL, USA) for 39 clinical chemistry tests and 17 immunoassays. Precision was evaluated at least at two concentration levels for 5 days in quintuplicate, following CLSI EP15-A3. Method comparison included parallel analysis of leftover routine samples on Alinity analyzers and the previously used Cobas c501 and e601 (Roche Diagnostics, Mannheim, Germany). Linearity was tested by preparing sequential sample dilutions with high analyte concentration, following the CLSI EP6 document. For clinical chemistry tests, within-run coefficients of variation (CV) were up to 6.0% (beta-2-microglobulin), while between-run CVs up to 5.4% (immunoglobulin M). Among immunoassays, the highest within-run CV was obtained for vitamin B12 (6.9%), while between-run for CA 19-9 (4.3%). Complete agreement with Roche analyzers was observed for 16 (41%) clinical chemistry assays and 6 (35%) immunoassays. Half of all evaluated assays did not meet the desirable biological variation criteria for bias, being especially exceeded for alpha1-antitrypsin, apolipoprotein A1, ceruloplasmin, complement C3 and C4, hemoglobin A1c, lipoprotein (a) and myoglobin, as well as some tumor markers (CA 125, CEA, fPSA, AFP, and ferritin), hormones (cortisol, DHEA-S, insulin) and vitamins (25-OHD). Linearity in the tested ranges was confirmed. Overall, this study revealed that precision criteria derived from manufacturer's claims were not satisfied for all assays while comparison study for some assays yielded differences that imply the need for additional assay evaluation prior to introduction into routine practice.

Haemoglobin A1c-based screening for prediabetes and diabetes mellitus: a multi-center study in Croatian adult population.

INTRODUCTION: Based on the hypothesis that there is a substantial rate of adults with prediabetes and undiagnosed diabetes mellitus (DM), our aim was to perform haemoglobin A1c (HbA1c)-based screening in a cohort of Croatian adults and estimate the prevalence of prediabetes and undiagnosed DM according to American Diabetes Association criteria. MATERIALS AND METHODS: This multi-center, cross-sectional study performed in six Croatian hospitals included 5527 patients aged 40 to 70 years admitted to the Emergency Department or undergoing a primary care check-up. Haemoglobin A1c was measured from leftover whole blood samples using the enzymatic method on either Alinity c or Architect c-series analyser (Abbott Laboratories, Chicago, USA). Haemoglobin A1c between 39-47 mmol/mol was classified as prediabetes, while ≥ 48 mmol/mol as undiagnosed DM. RESULTS: After exclusion of 435 patients with known DM, the final cohort included 5092 patients (median age 57; 56% males). A total of 882 (17.3%) patients had HbA1c values between 39 and 47 mmol/mol. There were 214 (4.2%) patients with HbA1c ≥ 48 mmol/mol. Prediabetes prevalence ranged from 14.2% to 20.5%, while undiagnosed DM from 3.3% to 7.3%, with statistically significant differences among settings (P < 0.001). Age-stratified analysis showed that prediabetes and undiagnosed DM prevalence increase with age (P < 0.001), being 25.4% and 5.8%, respectively, in patients aged 60 to 70 years. CONCLUSION: Underlying impairment of glucose metabolism was identified in about one in five adults, with significant number of patients with already overt DM. These results should serve as a starting point for further steps directed towards promotion of preventive measures for DM in Croatia.

Serum procalcitonin in Philadelphia-negative myeloproliferative neoplasms.

Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are rare clonal hematopoietic stem cell disorders accompanied by a strong inflammatory milieu, which is directly responsible for constitutional symptoms associated with the disease, such as fever, weight loss or night sweats. Non-hematologists sometimes (and often wrongly) consider the fever in MPN patients to be a symptom of an underlying disease, which may have devastating consequences. Serum procalcitonin (PCT) is a circulating biomarker commonly used to improve the diagnostic accuracy of bacterial infections and to guide antibiotic therapy. The aim of this study was to test whether PCT could aid the clinician in the early diagnosis of bacterial infections in MPNs. This study investigated PCT in 41 ambulatory MPN patients (13 ET, 13 PV and 15 MF) who had no signs of infection and compared it to 10 MPN patients with microbiologically and/or serologically documented bacterial infections. Median PCT in MPN patients was 0.02 ng/mL (range 0.01-0.09 ng/mL). No difference in PCT was found between ET, PV and MF patients (p = 0.993), whereas MPN patients with documented bacterial infections had significantly higher PCT (median PCT 2.45, range 0.90-5.40 ng/mL) when compared to MPN patients with (median PCT 0.03 ng/mL) or without constitutional symptoms (median PCT 0.02 ng/mL; p < 0.001 for both analyses). These results clearly show that PCT should not be considered as a disease biomarker in MPNs and careful clinical assessment for the signs of infection is needed when MPN patients present with fever and high PCT.

Circulating YKL-40 in Philadelphia-negative myeloproliferative neoplasms.

Objectives: Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), are characterized by clonal myeloproliferation and a strong inflammatory atmosphere. YKL-40, expressed in granulocytes, macrophages, megakaryocytes and malignant cells, is an acute phase reactant with an important role in tissue remodeling and atherosclerotic inflammation. The aim of this study was to investigate serum YKL-40 levels in MPNs and to assess its clinical correlations. Methods: ELISA test was used to measure serum YKL-40 levels in 111 MPN patients and in 32 healthy controls. Results: Serum YKL-40 levels were higher in ET, post-ET MF, PV, post-PV MF and primary MF patients, when compared to healthy controls (p < 0.001). Higher serum YKL-40 levels were associated with parameters indicative of the increased inflammatory state (higher C-reactive protein, poor performance status, presence of constitutional symptoms and cardiovascular risk factors). Additionally, higher serum YKL-40 levels in MF patients were associated with blast phase disease, lower hemoglobin and higher Dynamic International Prognostic Scoring System score. In the multivariate Cox regression models, higher serum YKL-40 levels in ET and PV patients were independently associated with an increased risk of thrombosis (HR 4.64, p = 0.031) and impaired survival in MF patients (HR 4.31, p = 0.038). Conclusion: These results indicate that higher circulating YKL-40 levels in MPNs might have a pathophysiological role in disease progression and thrombosis development. Assessing circulating YKL-40 could help in identification of ET and PV patients at a high risk of future cardiovascular events and has a good potential for improving prognostication of MF patients.

Effectiveness of minimum retesting intervals in managing repetitive laboratory testing: experience from a Croatian university hospital.

INTRODUCTION: Inappropriate laboratory retesting can be addressed by implementing minimum retesting intervals (MRI). The aim of our study was to assess the effectiveness of the implemented MRI protocol for inpatients. MATERIALS AND METHODS: Minimum retesting intervals were applied for 53 laboratory tests. The overall reduction of test requests, reduction in charges and reagent cost savings, frequency of MRI alert appearance as well as the rate of MRI acceptance and ignorance were calculated for a one-year period. Reasons for violating the MRI rule, hospital departments that contributed mostly to MRI rule violation, and the frequency of MRI violations between routine and emergency laboratory were evaluated. RESULTS: During the one-year period, 106,780 requests violated the MRI rule, which corresponds to 14.8% of all requests received. 13,843 requests were cancelled, yielding a 1.9% reduction of requested tests. High-volume tests, namely complete blood count, C-reactive protein, alanine aminotransferase, gamma-glutamyltransferase and total bilirubin, accounted for 65% of all generated alerts and had the highest alert ignorance (>85%). The highest cancellation rate was observed for tumor markers and autoimmunity tests, for most being at least 50%. Annual charge reduction was 62,641 EUR while reagent cost savings were 11,408 EUR. Tests performed in the emergency laboratory had a higher alert appearance than the same routine tests. The most common reason for MRI violation was clinical justification based on the patient's condition. Most frequently ignored MRI alerts were in the intensive care unit. CONCLUSION: MRI implementation showed limited effectiveness in reducing testing repetition and achieving financial savings, yet provided the basis for future improvements.

Serum chitotriosidase: a circulating biomarker in polycythemia vera.

OBJECTIVES: Serum chitotriosidase activity (CHIT1) is a biomarker of macrophage activation with an important role in inflammation-induced tissue remodeling and fibrosis. Macrophages have been described to play a crucial role in regulating pathological erythropoiesis in polycythemia vera (PV). The aim of this study was to evaluate CHIT1 in patients diagnosed with Philadelphia-negative myeloproliferative neoplasms (MPNs). METHODS: Using fluorometric assay, we measured CHIT1 in 28 PV, 27 essential thrombocythemia (ET), 17 primary myelofibrosis (PMF), 19 patients with secondary myelofibrosis and in 25 healthy controls. RESULTS: CHIT1 was significantly higher in PV (p < .001) and post-PV myelofibrosis (MF) transformation (post-PV MF) (p = .020), but not in ET (p = .080), post-ET MF transformation (p = .086), and PMF patients (p = .287), when compared to healthy controls. CHIT1 in PV was positively correlated with hemoglobin (p = .026), hematocrit (p = .012), absolute basophil count (p = .030) and the presence of reticulin fibrosis in the bone marrow (p = .023). DISCUSSION: A positive correlation between CHIT1 and these distinct laboratory PV features might imply macrophages closely related to clonal erythropoiesis as cells of CHIT1 origin. In addition, a positive association between CHIT1 and reticulin fibrosis might indicate its potential role in PV progression. CONCLUSION: CHIT1 might be considered as a circulating biomarker in PV. Additional studies are needed to clarify the role of CHIT1 in promoting disease progression and bone marrow fibrosis in PV.

Changing the electronic request form proves to be an effective tool for optimizing laboratory test utilization in the emergency department.

OBJECTIVES: Appropriate laboratory utilization more often than not needs to be initiated by the laboratory. This study was performed to analyze the impact on test ordering patterns in the emergency department obtained by omitting certain tests from the electronic tick box request form. The tests could still be ordered by writing the full name of the test or by a phone call. METHODS: Erythrocyte sedimentation rate (ESR), fibrinogen, aspartate aminotransferase (AST), calcium and lipase were omitted from the electronic request form and could subsequently be ordered either by phone or a typed-in request. A reflex testing protocol was elaborated for reduction of creatine kinase (CK) and CK-MB analyses. All interventions were introduced with prior consultation with clinical staff and according to current guidelines. The reduction of test orders and costs in the post-intervention period was assessed. All data were retrieved retrospectively from the laboratory information system (LIS). RESULTS: Disappearance from the tick box request form resulted in a significant decrease in the number of requests for targeted tests in the post-intervention year, mostly affecting AST and fibrinogen (83% and 79% reduction of ordering, respectively), followed by a 58% reduction in calcium orders, and 54% and 43% reductions in ESR and lipase requests, respectively. A substantial reduction in CK requests was also observed, while CK-MB requests almost disappeared. Annual cost savings that emerged from all implemented interventions were estimated to be 19,445€. CONCLUSION: Significant reduction in ordering of selected tests was achieved simply by limiting their availability in hospital computerized order entry (COE) system. The present data suggest that removal of laboratory tests from the electronic request form can be an effective tool for changing physicians' test ordering behavior.