Detection of preanalytical errors in arterial blood gas analysis.

Introduction: Blood gas analysis (BGA) is an essential test used for years to provide vital information in critically ill patients. However, the instability of the blood gases is a problem. We aimed to evaluate time and temperature effects on blood gas stability. Materials and methods: Arterial blood was collected from 20 patients into syringes. Following BGA for baseline, syringes were divided into groups to stand at 4°C and 22°C for 30, 60, 90, 120 minutes. All were tested for pH, partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), oxygen saturation (sO2), oxyhemoglobin (O2Hb), sodium, potassium, glucose, lactate, oxygen tension at 50% hemoglobin saturation (p50), and bicarbonate. A subgroup analysis was performed to detect the effect of air on results during storage. Percentage deviations were calculated and compared against the preset quality specifications for allowable total error. Results: At 4°C, pO2 was the least stable parameter. At 22°C, pO2 remained stable for 120 min, pH and glucose for 90 min, lactate and pCO2 for 60 min. Glucose and lactate were stable when chilled. Air bubbles interfered pO2 regardless of temperatures, whereas pCO2 increased significantly at 22°C after 30 min, and pH decreased after 90 min. Bicarbonate, sO2, O2Hb, sodium, and potassium were the unaffected parameters. Conclusions: Correct BGA results are essential, and arterial sample is precious. Therefore, if immediate analysis cannot be performed, up to one hour, syringes stored at room temperature will give reliable results when care is taken to minimize air within the blood gas specimen.

The relationship between serum apelin levels and aortic dilatation in bicuspid aortic valve patients.

OBJECTIVE: The bicuspid aortic valve (BAV) is the most common congenital heart disease. The process of aortic dilatation is not completely clear in patients with the BAV. Apelin is a peptide found at high levels in vascular endothelial cells which has a role in vascular regulation and cardiovascular function. The aim of this study was to determine the relationship between serum apelin levels and ascending aortic dilatation in adult patients with BAV. DESIGN: This cross-sectional study included 62 patients with isolated BAV and to an age, gender, and body mass index-matched control group of 58 healthy volunteers with tricuspid aortic valve. Transesophageal echocardiography was performed on all patients to determine the type of BAV. Aortic diameters of the aortic root, sinus valsalva, sinotubular junction, and ascending aorta were evaluated with echocardiography. Patients with BAV were divided into two subgroups according to the aortic diameters, as the nondilated BAV group and the dilated BAV group. Serum apelin level was analyzed with ELISA method. RESULTS: The serum apelin levels of the BAV patients were significantly lower than those of the control group (833.5, 25th-75th percentile (713.5-1745) pg/dL vs 1669 (936-2543) pg/dL; P = 0.006). In the subgroup analysis, serum apelin level was significantly different between the nondilated BAV group and the dilated BAV group [977 (790-2433) pg/dL vs 737 (693-870) pg/dL, P < 0.05] and between the dilated BAV group and the control group [737 (693-870) pg/dL vs 1669 (936-2543) pg/dL, P < 0.001]. In multivariate logistic regression analysis apelin [7.27 (95% CI: 1.73-30.42), P = 0.007] and age [1.05 (95% CI: 0.99-1.20), P = 0.049] were determined as independent predictors for ascending aortic dilatation. CONCLUSION: Low serum apelin level was associated with dilatation of ascending aortic in BAV patients. However, apelin was not relevant to BAV without aortic dilatation.

The effect of extremely high glucose concentrations on 21 routine chemistry and thyroid Abbott assays: interference study.

INTRODUCTION: Extremely high glucose concentrations have been shown to interfere with creatinine assays especially with Jaffe method in peritoneal dialysate. Because diabetes is the fastest growing chronic disease in the world, laboratories study with varying glucose concentrations. We investigated whether different levels of glucose spiked in serum interfere with 21 routine chemistry and thyroid assays at glucose concentrations between 17-51 mmol/L. MATERIALS AND METHODS: Baseline (group I) serum pool with glucose concentration of 5.55 (5.44-5.61) mmol/L was prepared from patient sera. Spiking with 20% dextrose solution, sample groups were obtained with glucose concentrations: 17.09, 34.52, and 50.95 mmol/L (group II, III, IV, respectively). Total of 21 biochemistry analytes and thyroid tests were studied on Abbott c8000 and i2000sr with commercial reagents. Bias from baseline value was checked statistically and clinically. RESULTS: Creatinine increased significantly by 8.74%, 31.66%, 55.31% at groups II, III, IV, respectively with P values of < 0.001. At the median glucose concentration of 50.95 mmol/L, calcium, albumin, chloride and FT4 biased significantly clinically (-0.85%, 1.63%, 0.65%, 7.4% with P values 0.138, 0.214, 0.004, < 0.001, respectively). Remaining assays were free of interference. CONCLUSION: Among the numerous biochemical parameters studied, only a few parameters are affected by dramatically increased glucose concentration. The creatinine measurements obtained in human sera with the Jaffe alkaline method at high glucose concentrations should be interpreted with caution. Other tests that were affected with extremely high glucose concentrations were calcium, albumin, chloride and FT4, hence results should be taken into consideration in patients with poor diabetic control.

Clinical biochemistry laboratory rejection rates due to various types of preanalytical errors.

INTRODUCTION: Preanalytical errors, along the process from the beginning of test requests to the admissions of the specimens to the laboratory, cause the rejection of samples. The aim of this study was to better explain the reasons of rejected samples, regarding to their rates in certain test groups in our laboratory. MATERIALS AND METHODS: This preliminary study was designed on the rejected samples in one-year period, based on the rates and types of inappropriateness. Test requests and blood samples of clinical chemistry, immunoassay, hematology, glycated hemoglobin, coagulation and erythrocyte sedimentation rate test units were evaluated. Types of inappropriateness were evaluated as follows: improperly labelled samples, hemolysed, clotted specimen, insufficient volume of specimen and total request errors. RESULTS: A total of 5,183,582 test requests from 1,035,743 blood collection tubes were considered. The total rejection rate was 0.65 %. The rejection rate of coagulation group was significantly higher (2.28%) than the other test groups (P < 0.001) including insufficient volume of specimen error rate as 1.38%. Rejection rates of hemolysis, clotted specimen and insufficient volume of sample error were found to be 8%, 24% and 34%, respectively. Total request errors, particularly, for unintelligible requests were 32% of the total for inpatients. CONCLUSIONS: The errors were especially attributable to unintelligible requests of inappropriate test requests, improperly labelled samples for inpatients and blood drawing errors especially due to insufficient volume of specimens in a coagulation test group. Further studies should be performed after corrective and preventive actions to detect a possible decrease in rejecting samples.

Effect of renal failure on N-terminal Pro-Brain natriuretic peptide in patients admitted to emergency department with acute dyspnea.

OBJECTIVE: Preexisting renal failure diminishes the excretion of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP), therefore limits the diagnostic value of this peptide for concomitant heart failure. The aim of this study was to evaluate the association between NT-proBNP and the stages of renal dysfunction in a typical population attended to emergency department with acute dyspnea. METHODS: In this cross-sectional study, all consecutive patients with acute dyspnea underwent clinical evaluation, laboratory assessment of NT-proBNP, and echocardiographic examinations. Among subjects, 54.5% were diagnosed as heart failure. Grouping variables according to renal function capacity and ejection fraction, independent variables were compared with Kruskal-Wallis or ANOVA with posthoc tests. Correlation and linear regression analysis were done to analyze the variables associated with NT-proBNP. The diagnostic performance of NT-proBNP was evaluated by receiver-operating characteristic (ROC) curve. RESULTS: Serum median NT-proBNP level in patients with severe renal impairment was significantly higher than moderate and mildly decreased renal functions (p=0.001). In patients with moderate and severe left ventricular failure, NT-proBNP was significantly higher compared with normal subjects (LVEF>50%) (p=0.040, and 0.017, respectively). Renal dysfunction was associated in 56% of patients with heart failure. The area under the ROC curve of NT-proBNP for identifying left ventricular failure in patients with renal failure (eGFR<90 mL/min/1.73 m2) was 0.649 and reached significant difference (95% CI:0.548-0.749, p=0.005). CONCLUSION: In addition to NT-proBNP measurement in clinical judgement of heart failure, renal functions have to be taken into consideration to avoid misdiagnosis.

The anti-inflammatory and antioxidant effects of pravastatin and nebivolol in rat aorta.

OBJECTIVE: The aim of this study was to investigate the effects of pravastatin and nebivolol in the atherosclerotic process including inflammation and oxidative stress in rat aorta. METHODS: This experimental randomized controlled study comprised of 35 Wistar albino rats. Nω-nitro-L-arginine methyl ester (L-NAME) - induced vascular inflammation and arteriosclerosis were treated with both of the pharmacologic agents. All were divided into 5 equal groups: the control, group I: L-NAME -15 days, group II: L-NAME 30+ nebivolol, group III: L-NAME -30+ pravastatin, group IV: L-NAME - 30 days. Serum ceruloplasmin, uric acid, total antioxidant capacity (TAC), total cholesterol (T.Chol), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG) were analyzed. Medial thickening and leukocyte infiltration status were examined histopathologically. The results were compared with control group and with each other using Kruskal-Wallis and Mann-Whitney U test. RESULTS: Pravastatin diminished the rise of ceruloplasmin, which was taken as an index of inflammation (p=0.002). Pravastatin and nebivolol decreased the L-NAME induced oxidative stress (p=0.001, 0.002, respectively). Nebivolol diminished the rise of LDL (p=0.04). Pravastatin lowered T.Chol, LDL and TG levels (p=0.001, 0.008, 0.040, respectively). HDL values were not changed significantly. CONCLUSION: In conclusion, 15 days of statin therapy attenuated vascular inflammation and lowered the rised lipid levels (LDL, T.cholesterol and TG). Both the nebivolol and pravastatin exhibited antioxidant property. These documented beneficial effects of both of the drugs may improve the clinical outcomes of patients with hypertension or hyperlipidemia by additional studies.

The anti-inflammatory and antioxidant effects of pravastatin and nebivolol in rat aorta.

OBJECTIVE: The aim of this study was to investigate the effects of pravastatin and nebivolol in the atherosclerotic process including inflammation and oxidative stress in rat aorta. METHODS: This experimental randomized controlled study comprised of 35 Wistar albino rats. Nω-nitro-L-arginine methyl ester (L-NAME) - induced vascular inflammation and arteriosclerosis were treated with both of the pharmacologic agents. All were divided into 5 equal groups: the control, group I: L-NAME -15 days, group II: L-NAME 30+ nebivolol, group III: L-NAME -30+ pravastatin, group IV: L-NAME - 30 days. Serum ceruloplasmin, uric acid, total antioxidant capacity (TAC), total cholesterol (T.Chol), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG) were analyzed. Medial thickening and leukocyte infiltration status were examined histopathologically. The results were compared with control group and with each other using Kruskal Wallis and Mann-Whitney U test. RESULTS: Pravastatin diminished the rise of ceruloplasmin, which was taken as an index of inflammation (p=0.002). Pravastatin and nebivolol decreased the L-NAME induced oxidative stress (p =0.001, 0.002, respectively). Nebivolol diminished the rise of LDL (p=0.04). Pravastatin lowered T.Chol, LDL and TG levels (p=0.001, 0.008, 0.040, respectively). HDL values were not changed significantly. CONCLUSION: In conclusion, 15 days of statin therapy attenuated vascular inflammation and lowered the rised lipid levels (LDL, T.cholesterol and TG). Both the nebivolol and pravastatin exhibited antioxidant property. These documented beneficial effects of both of the drugs may improve the clinical outcomes of patients with hypertension or hyperlipidemia by additional studies.

Comparing the renal safety of isoosmolar versus low-osmolar contrast medium by renal biomarkers N-acetyl-ß-D-glucosaminidase and endothelin.

Iodixanol and iopamidol are commonly used contrast agents in coronary angiography. We evaluated the nephrotoxic effects of both contrast media in relation to renal biomarkers. A total of 38 low-risk patients who underwent coronary angiography were enrolled. Patients were randomized to receive either low-osmolar nonionic monomer or isoosmolar nonionic dimer contrast medium. N-Acetyl-ß-d-glucosaminidase (NAG), endothelin, blood urea nitrogen, and urine and serum creatinine (SCr) levels were measured before  the procedure (T0), at 6 hours (T6), and at 1 year after the procedure. Plasma endothelin, urine NAG/creatinine, and SCr were higher; accordingly, the urine creatinine values were lower in both the groups when comparing T0 versus T6. The groups were similar with each other when comparing T0 and T6 values. Both the contrast agents may be safely used at a low volume for coronary angiography in low-risk patients. Endothelin and NAG are sensitive to acute renal changes in function. There is a need for further prospective investigations with more patients.

Prognostic significance of circulating tumor cells and serum CA15-3 levels in metastatic breast cancer, single center experience, preliminary results.

BACKGROUND: Breast cancer is the second leading cancer causing death in women. Circulating tumor cells are among the prognostic factors while tumor markers are of diagnostic value and can be used for follow-up. The aim of this study was to investigate the correlation between the prognostic significance of the serum CA15-3 levels, number of circulating tumor cells and histopathological tumor factors. MATERIALS AND METHODS: Thirty patients recently diagnosed with breast cancer were included in the study. Number of circulating tumor cells and serum CA15-3 level were assessed when metastasis was detected and diagnostic value was assessed. Presence of associations with estrogen and progesterone receptors, c-erbB2, Ki-67 proliferation index and histological grade were also evaluated. RESULTS: Median overall survival of the patients with serum CA15-3 levels of >108 ng/dl was 19 months whereas for those with a low serum level it was 62 months. Median overall survival for CTC ≥5vs CTC<5 patients was 19 months and 40 months respectively. The difference between the two groups was statistically significant. CONCLUSIONS: Prognostic significance of the CTC count and CA15-3 levels in metastatic breast cancer patients was demonstrated.

The effect of storage time and freeze-thaw cycles on the stability of serum samples.

INTRODUCTION: Optimal storage of serum specimens in central laboratories for a long period for multicenter reference interval studies, or epidemiologic studies remains to be determined. We aimed to examine the analytical stability of chemistry analytes following numerous freeze-thaw and long-term storage. MATERIALS AND METHODS: Serum samples were obtained from 15 patients. Following baseline measurement, sera of each subject were aliquoted and stored at -20 degrees C for two experiments. A group of sera were kept frozen for up to 1, 2 and 3 months and then analyzed for stability. The other experiment consisted of one to ten times of freeze and thaw cycles. Total of 17 chemistry analytes were assayed at each time point. The results were compared with those obtained from the initial analysis of fresh samples. Median or mean changes from baseline (T(0)) concentrations were evaluated both statistically and clinically according to the desirable bias. RESULTS: Of the analytes studied, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), gamma-glutamyl transferase (GGT), direct bilirubin, glucose, creatinine, cholesterol, triglycerides, high density lipoprotein (HDL) were stable in all conditions. Blood urea nitrogen (BUN), uric acid, total protein, albumin, total bilirubin, calcium, lactate dehydrogenase (LD) were changed significantly (P < 0.005). CONCLUSIONS: As a result, common clinical chemistry analytes, with considering the variability of unstable analytes, showed adequote stability after 3 months of storage in sera at -20 degrees C, or up to ten times of freeze-thaw cycle. All the same, such analysis can only be performed for exceptional cases, and this should be taken into account while planning studies.

Cardiovascular risk factors in young male adults: impact of physical activity and parental education.

BACKGROUND: This study was conducted to assess whether choices of physical activity, smoking status, and parental education and income were correlated with the health status of young adult males which are important for preventive health policy. METHODS: 491 18-29-year old males from lower socioeconomical districts in Turkey participated in this study. Information about demographic characteristics, parental education, household income, smoking status, and physical activity was obtained by means of a standardized questionnaire. BMI and metabolic parameters (serum lipid profile) were assessed. RESULTS: Mean total cholesterol, LDL, HDL and triglyceride levels were in the normal range. The physically active group displayed a better lipid profile. No relationship was found between parental education and serum lipids. Smoking was slightly correlated with household income (r=103, p=0.022). CONCLUSION: Young adult males who participate in relatively high levels of physical activity are at lower CHD risk than less active ones. The present study also showed that lower socioecnomic status does not always correlate with higher levels of cardiovascular risk factors. In conclusion, data supports that while family history cannot be changed, HDL levels can be modulated by lifestyle factors as in other populations and that with the determined benefits of increasing physical activity and thus, HDL levels, policy reform in schools to promote physical activity are warranted.

Stability studies of common biochemical analytes in serum separator tubes with or without gel barrier subjected to various storage conditions.

INTRODUCTION: The collected and shipped blood samples are exposed to a various extra-analytical factors prior to analysis. The aim of the study was to determine the stability of analytes in serum gel tubes and plain tubes exposed to a range of storage temperatures and times after centrifugation. MATERIALS AND METHODS: Fifteen healthy volunteers were recruited and venous blood was collected into four tubes, two with and two without gel separator. Analyzing the baseline samples in 30 min, all were stored at 4 degrees C or 24 degrees C for 6, 12, 18, 24, 30, 36, 48 and 72 hours and 1 week. Sixteen biochemical anaytes were measured on each sample. Variations remained under the desirable bias considered as clinically insignificant. RESULTS: On day three, most analytes remained stable including albumin, protein, creatinine, cholesterol, triglycerides, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), creatine kinase (CK), lactate dehydrogenase (LD) regardless of tube types. Glucose concentration decreased markedly (P = 0.001) beginning from the first hours of storage in plain serum. The stability maximized for the analytes including glucose, total bilirubin, urea nitrogen (BUN), uric acid stored at 4 degrees C in gel tubes. Aspartate aminotransferase (AST) activity increased significantly (P = 0.002) up to 48-h, however bias was not significant clinically. High density lipoprotein (HDL) concentration was stable in gel tubes at 24 degrees C, in plain tubes at 4 degrees C stored up to 36-h. CONCLUSION: Serum gel or non-gel tubes might be used interchangeably for 11 analytes chilled or at 24 degrees C, whereas some restrictions must be applied for glucose, AST, BUN, HDL, and uric acid.

Effects of hemolysis interferences on routine biochemistry parameters.

INTRODUCTION: Hemolysis is still the most common reason for rejecting samples, while reobtaining a new sample is an important problem. The aim of this study was to investigate the effects of hemolysis in different hemolysis levels for mostly used biochemical parameters to prevent unnecessary rejections. MATERIALS AND METHODS: Sixteen healthy volunteers were enrolled in the study. Four hemolysis levels were constituted according to hemoglobin concentrations and they were divided into five groups: Group I: 0-0.10 g/L, Group II:0.10-0.50 g/L, Group III: 0.51-1.00 g/L, Group IV: 1.01-2.50 g/L, Group V: 2.51-4.50 g/L. Lysis was achieved by mechanical trauma. RESULTS: Hemolysis interference affected lactate dehydrogenase (LD) and aspartate aminotransferase (AST) almost at undetectable hemolysis by visual inspection (plasma hemoglobin < 0.5 g/L). Clinically meaningful variations of potassium and total bilirubin were observed in moderately hemolyzed samples (hemoglobin > 1 g/L). Alanine aminotransferase (ALT), cholesterol, gamma glutamyltransferase (GGT), and inorganic phosphate (P) concentrations were not interfered up to severely hemolyzed levels (hemoglobin: 2.5-4.5 g/L). Albumin, alkaline phosphatase (ALP), amylase, chloride, HDL-cholesterol, creatine kinase (CK), glucose, magnesium, total protein, triglycerides, unsaturated iron binding capacity (UIBC) and uric acid differences were statistically significant, but remained within the CLIA limits. CONCLUSION: To avoid preanalytical visual inspection for hemolysis detection, improper sample rejection, and/or rerun because of hemolysis, it is recommended in this study that, routine determination of plasma or serum free hemoglobin concentrations is important. For the analytes interfered with hemolysis, new samples have to be requested.