Clinical Usefulness of Direct/Total Bilirubin Ratio

BACKGROUND: The direct/total (d/t) bilirubin ratio can be used to distinguish the causes of jaundice in many patients who have increased levels of direct and indirect bilirubin. However, the reference range of the d/t ratio has not been established, hindering its clinical usefulness. This study assessed the clinical usefulness of the d/t ratio. METHODS: Paired total bilirubin and direct bilirubin tests (N=4,357) of cholestasis, hemolytic anemia, and neonatal jaundice were evaluated. Regression analyses were performed between total bilirubin and direct bilirubin, and between total bilirubin and the d/t ratio for each disease. Theoretical correlation models were established and used to compare the regression analyses data. RESULTS: The theoretical model and regression equation between total bilirubin and direct bilirubin displayed linear correlations for all three cholestatic diseases. The model and regression equation between total bilirubin and the d/t ratio showed reciprocal curve correlations for the cholestatic diseases. When the total bilirubin concentration exceeded approximately 10 mg/dL, the rate of change of the d/t ratio decreased and converged to a constant value between 0.7 and 0.9. CONCLUSIONS: If the total bilirubin concentration exceeds 10 mg/dL, cholestatic diseases can be diagnosed if the d/t ratio is more than 0.7. However, if the total bilirubin concentration is lower than 10 mg/dL, cholestatic diseases should be considered even if the d/t ratio is lower than 0.7. Therefore, use of the d/t ratio with total bilirubin could prove to be valuable in clinical settings.

Evaluation of a Test Index Obtained by Coupling Protein with Specific Gravity of Screening Urine Test

BACKGROUND: The 24-hr urine protein excretion test is regarded as a standard for quantitative urinary protein analysis; however, collection of urine over 24 hr is troublesome and errors may occur during the process. We obtained a test index reflecting diluted or concentrated urine by coupling the results of a simple and rapid routine urine analysis and evaluated its usefulness as a marker that quantitatively reflects the 24-hr urine protein excretion. METHODS: The estimated urine protein-osmolality ratio (Pro/Osm) was obtained by two linear regression equations between urine dipstick protein and natural logarithm of the protein concentration, and between urine specific gravity (SG) and urine osmolality (Osm). Sensitivity and specificity of 'estimated urine Pro/Osm' and the widely used urine protein-creatinine ratio were evaluated for their efficiency in diagnosing pathological proteinuria and nephrotic proteinuria based on 24-hr urine protein excretion. RESULTS: Moderate correlations were noted between protein concentration determined by the urine dipstick protein assay and natural logarithm of protein concentration (r=0.86) and between urine SG and urine Osm (r=0.74). The receiver operating characteristics analysis showed that an estimated urine Pro/Osm value of 0.045 had a sensitivity of 91.1% and a specificity of 88.6% for diagnosing pathological proteinuria, and a value of 0.204 had a sensitivity of 100% and a specificity of 80.4% for diagnosing nephrotic proteinuria. CONCLUSIONS: Coupling the results of urine dipstick protein and urine SG determined by the routine analysis will provide additional useful information that will make the screening of renal diseases more cost-effective.

Alterations of Complement C3 and C4 Levels in Delayed Testing

BACKGROUND: In vitro levels of complement C3 and C4 proteins are sensitive to storage conditions. To avoid in vitro complement activation when testing is delayed, serum should be frozen at -20degrees C within 2 hr of venipuncture. However, this is impractical in routine laboratory work. Therefore, we investigated alterations in C3 and C4 levels in refrigerated specimens over time and derived formulae to estimate initial levels of complement concentrations in delayed testing. METHODS: Ten fresh specimens were measured for C3 and C4 concentrations and were refrigerated at 4degrees C. We measured C3 and C4 levels in refrigerated samples daily for 4 days using an automated nephelometer (Beckman Coulter Inc., USA). RESULTS: C3 and C4 levels were significantly increased over time in refrigerated specimens (P<0.001, P<0.001, respectively). The increments in C3 and C4 levels were described by the equations: C3 (mg/dL)=3.55x+87.18 (r=0.9909), and C4 (mg/dL)=0.72x+22.3 (r=0.9395), where x=the number of days samples were refrigerated before testing. Increases in C3 and C4 concentrations were described on a percentage basis by the equations: DeltaC3 (%)=4.14x+1.07 (r=0.9903), and DeltaC4 (%)=3.57x+2.48 (r=0.9405). CONCLUSIONS: As the measured C3 and C4 concentrations increased by 3.55 mg/dL (4.1%) and 0.72 mg/dL (3.6%) per day in refrigerated specimens, the levels of C3 and C4 should be adjusted in delayed testing. We proposed that the formulae presented be used to back-calculate initial levels of C3 and C4 concentrations.

Comparison of the Characteristics of Patients with diabetes as Diagnosed Using Three Different Tests

BACKGROUND: Diabetes diagnosis can be made using different laboratory tests, including the fasting plasma glucose (FPG) test, 75-g 2-h oral glucose tolerance test (2-h OGTT), and hemoglobin A1c (HbA1c) test; however, these tests have different meanings. This study aimed at comparing patient characteristics based on the diagnosis using each of these 3 tests. METHODS: A total of 750 adults suspected of having diabetes and aged > or =18 years underwent the following tests on the same day: FPG, 2-h OGTT, HbA1c, insulin, general chemistry, and routine urinalysis. The patients were divided into 8 groups based on the combination of positive and negative results of each of the 3 tests, and the characteristics of the patients were compared among groups. RESULTS: In the group that tested positive for all 3 tests, the FPG, 2-h OGTT, HbA1c, homeostasis model assessment for insulin resistance, alanine transaminase, triglyceride, and urine glucose positive values were higher than those of the group that tested positive using the 2-h OGTT and HbA1c test. In the group that tested positive using the 2-h OGTT, blood urea nitrogen was higher than that of the group that tested positive using the HbA1c test. CONCLUSIONS: The characteristics of the patients differed between the tests that yielded positive diagnostic results. This may be related to the fact that the 3 tests indicate different states of glucose metabolism. The results of the 3 tests were significantly different; therefore, it may be more effective to combine the results of the 3 tests to comprehensively describe patient characteristics.

Evaluation of the Clinical Significance of Ketonuria

BACKGROUND: Urine ketone test is commonly used to screen for diabetic ketoacidosis (DKA). Ketonuria also develops in patients with disease conditions other than DKA. However, the prevalence of DKA in patients with ketonuria is not known. We investigated the prevalence of ketonuria and characteristics of patients with ketonuria and estimated the prevalence of DKA among them to study the clinical significance of ketonuria as an indicator of DKA. METHODS: We studied 1,314 adult and 1,027 pediatric patients who underwent urinalysis. The prevalence of ketonuria in the different groups of patients, classified according to the types of their visits to the institution, was investigated, and the relationships between ketonuria and albuminuria, glycosuria, and bilirubinuria were evaluated. RESULTS: The overall prevalence of ketonuria was 9.1%. The prevalences of ketonuria in adult and pediatric patients were 4.3% and 15.2%, respectively. The prevalences of ketonuria were the highest in the adult (9.7%) and pediatric (28%) patients in the group that had visited the emergency department. Among patients with ketonuria, 7% adult and 3.8% pediatric patients showed glycosuria. CONCLUSIONS: This study showed that the prevalence of DKA in patients with ketonuria, defined as the simultaneous presence of ketone bodies and glucose in urine, was only 7%. Therefore, we concluded that ketonuria might be clinically significant as an indicator of acute or severe disease status rather than of DKA.

Annual Report on External Quality Assessment in Clinical Chemistry in Korea (2009) / 임상검사와정도관리

Six trials with 3 samples for each trial for external quality assessment of general chemistry and blood gas were performed in 2009. All the control materials were sent in specifically-made boxes at the same time. The response rates were 87.5% in general chemistry and 89.3% in blood gas. The items included sodium, potassium, chloride, BUN, glucose, calcium, phosphorus, uric acid, creatinine, bilirubin, total protein, albumin, total cholesterol, triglyceride, AST, ALT, ALP, LD and GGT in general chemistry and pH, pCO2 and pO2 in blood gas. Compared with the previous year (2008), change of the methods of analysis was not remarkable. The peer group coefficient of variation and the VIS scores of general chemistry items were slightly improved.

A Case of Pure Red Cell Aplasia Associated with Angioimmunoblastic T-cell Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

Pure red cell aplasia is a bone marrow failure characterized by a progressive normocytic anemia and reticulocytopenia without leucopenia and thrombocytopenia. It is associated with various hematologic diseases. However, pure red cell aplasia with angioimmunoblastic T cell lymphoma has rarely been reported. Here we describe a 43-year-old woman with pure red cell aplasia associated with angioimmunoblastic T-cell lymphoma. She had severe anemia (hemoglobin 6.9 g/dL) and a low reticulocyte count (0.2%). Direct and indirect Coombs' tests were positive. A CT scan of the abdomen revealed marked hepatosplenomegaly and small multiple lymphadenopathies. A bone marrow biopsy revealed focal infiltration of abnormal lymphoid cells and absence of red cell precursors. Splenic biopsy was compatible with angioimmunoblastic T-cell lymphoma. Ultimately, diagnosis of pure red cell aplasia associated with angioimmunoblastic T-cell lymphoma was made. After initiating CHOP therapy, the patient achieved complete remission, which was accompanied, shortly thereafter, by a rise in hemoglobin levels which finally returned to normal.

Annual Report on External Quality Assessment in Clinical Chemistry in Korea (2008) / 임상검사와정도관리

Six trials with 3 samples for each trial for external quality assessment of general chemistry and blood gas were performed in 2008. All the control materials were sent in specifically-made boxes at the same time. The response rates were 93.5% in general chemistry and 88.1% in blood gas. The items included sodium, potassium, chloride, BUN, glucose, calcium, phosphorus, uric acid, creatinine, bilirubin, total protein, albumin, total cholesterol, triglyceride, AST, ALT, ALP, LD and GGT in general chemistry and pH, pCO2 and pO2 in blood gas. Compared with the previous year (2007), change of the methods of analysis and the peer group coefficient of variation was not remarkable and the VIS scores of general chemistry items were slightly improved.

Annual Report on External Quality Assessment in Clinical Chemistry in Korea (2007) / 임상검사와정도관리

Six trials with 3 samples for each of external quality assessment for general chemistry and blood gas were performed in 2007. All the control materials were sent in specifically-made boxes at the same time. The response rates were 92.0% in general chemistry and 95.5% in blood gas. The items included sodium, potassium, chloride, BUN, glucose, calcium, phosphorus, uric acid, creatinine, bilirubin, total protein, albumin, total cholesterol, triglyceride, AST, ALT, ALP, LD and GGT in general chemistry and pH, pCO2 and pO2 in blood gas. Compared with the previous year (2006), the methods of analysis were slightly changed and the coefficient of variation and VIS scores of general chemistry items were not significantly changed.

Pseudohyperphosphatemia in a Patient with Multiple Myeloma

Hyperphosphatemia is an unusual manifestation in patients with multiple myeloma without a significantly reduced glomerular filtration rate. Serum phosphate may be falsely elevated when a large amount of paraproteins is present in the serum, because ultraviolet light absorbance is elevated with the phosphomolybdate ultraviolet assay, which is most commonly used for serum phosphate measurement. This pseudohyperphosphatemia can be confirmed by deproteinization of the serum of patients. We report a case of multiple myeloma presenting with spurious hyperphosphatemia revealing pseudohyperphosphatemia by deproteinization of serum using sulfosalicylic acid.

Difference of the Results of Two Visits in Down Syndrome Screening Test / 임상검사와정도관리

INTRODUCTION: Estimation of the risk of Down syndrome pregnancy by the triple marker test is performed on women once at anytime during the 15-21 weeks of gestational age. The triple marker test is based on the distribution of the alpha-fetoprotein (AFP), chorionic gonadotropin (CG) and unconjugated estriol (uE3) of the different pregnancy. In spite of the logical excellencies, various factors can affect the result of the test in practical field. We compared differences of the risk of Down syndrome pregnancy based on the specimen obtained from two visits during the 15-21 weeks of gestational age. METHOD: We measured the AFP, CG and uE3 with Access (Beckman Coulter, USA) from the sera of 104 pregnant women who visited two times about 2 weeks of interval during 15-21 weeks of gestational age. We calculated log (MoM) of AFP, CG and uE3 of each marker between two visits, and compared differences of each biochemical marker and difference of risk of Down syndrome pregnancy between two visits. RESULT: Mean+/-SD of log (MoM) of AFP, CG, uE3 of the 1st visit were 0.019+/-0.156, -0.016+/-0.224, 0.002+/-0.138, respectively, and those of AFP, CG, uE3 of the 2nd visit were 0.010+/-0.140, -0.076+/-0.205, 0.057+/-0.138, respectively. CG and uE3 showed statistically significant difference (P<0.001, P<0.001, respectively) but AFP did not (P=0.328). Risk of Down syndrome pregnancy of the 1st visit was 8.017x10(-4)+/-1.6241x10(-3), and that of the 2nd visit was 5.667x10(-4)+/-1.6241x10(-3), with no significant difference statistically (P=0.094). CONCLUSION: The risk of Down syndrome based on the sera of woman who visited two times about 2 weeks of interval between 15-21 weeks of gestational age did not show significant difference. It is resonable that triple marker test is performed on women once at anytime during the 15-21 weeks of gestational age in practical base.

Annual Report on External Quality Assessment in Clinical Chemistry in Korea (2005) / 임상검사와정도관리

Ten trials of external quality assessment for Clinical Chemistry in general chemistry and blood gas were performed in 2005. All the control materials were sent in specifically-made boxes at the same time. The response rates were 90.1% in general chemistry and 84.8% in blood gas. The items included sodium, potassium, chloride, BUN, glucose, calcium, phosphorus, uric acid, creatinine, bilirubin, total protein, albumin, total cholesterol, triglyceride, AST, ALT, ALP, LD and GGT in general chemistry and pH, pCO2 and pO2 in blood gas. Compared with the previous year (2004), the methods of analysis were changed and the coefficient of variation and VIS scores of general chemistry items were increased.

Annual Report on External Quality Assessment in Clinical Chemistry in Korea (2004) / 임상검사와정도관리

Ten trials of external quality assessment for Clinical Chemistry in general chemistry and blood gas were performed in 2004. All the control materials were sent in specifically-made boxes at the same time. The response rates were 92.0% in general chemistry and 86.0% in blood gas. The items included sodium, potassium, chloride, BUN, glucose, calcium, phosphorus, uric acid, creatinine, bilirubin, total protein, albumin, total cholesterol, triglyceride, AST, ALT, ALP, LD and GGT in general chemistry and pH, pCO2 and pO2 in blood gas. Compared with the previous year (2003), the methods of analysis are not changed much and the coefficient of variation and VIS scores of general chemistry items are decreased.

A Reestablished Reference Interval of Plasma Anion Gap Minimizing Preanalytical Errors / 대한진단검사의학회지

BACKGROUND: The reference interval of anion gap established in the 1970s has been changing as the method of electrolyte measurement changes. It is also influenced by preanalytical errors. But there are only a few reliable reports that examined the effect of various preanalytical errors. Furthermore, there has been no report of values measured by the instrument being used in our laboratory. Therefore, we attempted to establish a reference interval of anion gap measured by Hitachi 7170s minimizing preanalytical errors, and analyzed the effect of a delay in electrolyte measurement and of sample exposure to the air. METHODS: The subjects were 538 healthy people who attended Hanyang university hospital health clinic with normal blood levels for albumin, creatinine and glucose. The plasma Na+, K+, Cl-, and total carbon dioxide (TCO2) were measured by Hitachi 7170s autoanalyzer (Boehringer Mannheim, Indianapolis, USA). To examine the effect of the delay between blood withdrawal and electrolyte measurement and the loss of CO2 by exposure to the room air after bottle opening, the subjects were divided into group A (124 subjects) and group B (414 subject) whose electrolyte results were reported within and after 20 minutes, respectively, of blood withdrawal and the two groups were compared with each other for the electrolytes and anion gap. Anion gap was calculated by the formula, [Na+- (Cl-+TCO2)]. RESULTS: Compared with group A, TCO2 of group B decreased by 0.9 mmol/L (P<0.001) and the anion gap increased by 0.6 mmol/L (P=0.009). The reference interval of anion gap was established based on the group A at the value of 5.4-13.4 mmol/L. CONCLUSIONS: The reference interval of anion gap determined in this study was lower than the value commonly used and should be established with a minimum delay in electrolyte measurement and sample exposure to the air.

Annual Report on External Quality Assessment in Clinical Chemistry in Korea (2003) / 임상검사와정도관리

Ten trials of external quality assessment for Clinical Chemistry in general chemistry and blood gas were performed in 2003. All the control materials were sent in specifically-made boxes at the same time. The response rates were 90.3% in general chemistry and 91.8% in blood gas. The items included sodium, potassium, chloride, BUN, glucose, calcium, phosphorus, uric acid, creatinine, bilirubin, total protein, albumin, total cholesterol, triglyceride, AST, ALT, ALP, LD and GGT in general chemistry and pH, pCO2 and pO2 in blood gas. Compared with the previous year (2002), the methods of analysis are not changed much and the coefficient of variation and VIS scores of general chemistry items are decreased.

The Change of Concentration of Chemicals in the Refrigerated Urine / 임상검사와정도관리

BACKGROUND: Refrigeration is the most common method of preservation for 24 hour urine collection. We tried to find out if the concentrations of the frequently measured chemicals in urine refrigerated for 24 hours were different from those in fresh urine. METHODS: The concentration of calcium, phosphorus, uric acid, creatinine, sodium, potassium, chloride, and protein was measured in fresh urine specimens for routine urine analysis. After refrigeration of the rest of the urine specimens for 24 hours, the same tests were performed, and the results of them were compared with those of fresh urine. Some urine specimens showed precipitation and decreased uric acid concentration after precipitation, and the chemical properties of them were determined statistically. RESULTS: The concentrations of the protein, phosphorus, creatinine, sodium, potassium, and chloride of refrigerated urine was not different statistically from those of the fresh one, but calcium and uric acid showed statistical difference between fresh and refrigerated samples (P<0.05). Urine specimens with precipitation and decreased uric acid showed chemical characteristics of high uric acid concentration and low pH. CONCLUSIONS: For the measurements of total protein, phosphorus, creatinine, sodium, potassium, and chloride, the urine can be refrigerated while collection of 24 hours, but additional procedure is recommended for the measurement of calcium and uric acid.

External Quality Control for PT and aPTT in a Peer Group Using In-house / 대한진단검사의학회지

BACKGROUND: Coagulation studies are affected by the reagents and coagulometers that are used in the tests and it is therefore essential to compare the results within a peer group that uses the same reagents and coagulometer for an external quality control program. Because the domestic quality control program encompasses many different groups using different reagents and coagulometers, no comparison has been made among peer groups. Therefore, the authors performed a quality control program using in-house lyophilized plasma in a selected peer group. METHODS: Prothrombin times (PT) and activated partial thromboplastin times (aPTT) were tested using in-house normal and oral anticoagulant lyophilized plasma; the tests were performed for 50 consecutive days in four hospitals that were using the same coagulometer. The same PT reagents were used in all four hospitals. The international sensitivity index (ISI) was 1.32 for three hospitals and 1.47 for one hospital. Three hospitals used the same aPTT reagent. RESULTS: After lyophilization, there was no change in the PT results, but aPTT results were greatly prolonged. At four hospitals, the average international normalized ratio (INR) of normal lyophilized plasma was 0.94, 0.94, 0.95, and 0.82, while the average INR of oral anticoagulant lyophilized plasma was 2.18, 2.28, 2.21, and 1.87. The mean normal PT (MNPT) of three hospitals with ISI of 1.32 were 12.4s, 11.2s, and 12.3s, while the MNPT of one hospital with ISI of 1.47 was 12.5s. Average aPTT of normal plasma were 32.1s, 45.9s, 44.7s, and 44.3s while that of the oral anticoagulant plasma were 42.6s, 61.3s, 57.8s, and 55.6s. CONCLUSIONS: Since there are a great deal of difference in the results of coagulation study among the hospitals using the same reagents and coagulometers, it is utmost necessary to enforce a national level coagulation study quality control program in order to adopt proper oral anticoagulation therapy.

A Method for Measuring Uric Acid Accurately in Refrigerated Urine Specimens / 대한진단검사의학회지

BACKGROUND: There have been many reports about the decrease in uric acid concentration in refrigerated urine specimens as compared to fresh urine. In an effort to correct this problem, pre-treatment steps such as the pre-alkalinization of sample tubes or the pre-dilution of urine were recommended before the refrigeration. The authors sought to find a way to correct the decreased measurement of uric acid concentrations in the refrigerated urine samples. METHODS: The uric acid concentrations of 53 fresh urine samples were measured and all were refrigerated. After 24 hours of refrigeration, the samples were measured for their uric acid concentrations (the refrigerated samples). All samples were then mixed well with 1 M NaOH 20 microL/mL (the refrigerated-alkalinized samples) and they were again measured for their uric acid concentrations. The differences of uric acid concentrations between the fresh urine samples and the refrigerated samples and also between the fresh urine samples and the refrigerated-alkalinized samples were noted. RESULTS: In a precipitated group of 14 urine samples, the compared results between the fresh urine and the refrigerated urine showed a statistically significant difference (P<0.05). However, there were no significant differences between the fresh urine and the refrigerated-alkalinized urine (P=0.49). In a non-precipitated group, there were no significant differences between the fresh urine and the refrigerated urine, or between the fresh urine and the refrigerated-alkalinized urine (P=0.47, P=0.18). CONCLUSIONS: For 24 hour refrigerated urine samples, the addition of 1 M NaOH 20 microL/mL to the urine samples after refrigeration was recommended for accurate measurement of uric acid concentration.

Annual Report on External Quality Assessment in Clinical Chemistry in Korea (2002) / 임상검사와정도관리

Ten trials of external quality assessment for Clinical Chemistry in general chemistry and blood gas were performed in 2002. All the control materials were sent in specially-made boxes at the same time. The response rates were 81.2% in general chemistry and 85.7% in blood gas. The items included sodium, potassium, chloride, BUN, glucose, calcium, phosphorus, uric acid, creatinine, bilirubin, total protein, albumin, total cholesterol, triglyceride, AST, ALT, ALP, LD and GGT in general chemistry and pH, pCO2 and pO2 in blood gas. Compared with the previous year(2001), the methods of analysis are not changed much and the coefficient of variation and VIS scores of general chemistry items show no significant change.

Analytical and Clinical Evaluation of Lana(TM), the Reagent Measuring 1,5-Anhydroglucitol / 대한임상병리학회지

BACKGROUND: There have been many reports that 1,5-Anhydroglucitol (1,5-AG) was a better marker than the hemoglobin A1c (HbA1c) or fructosamine for monitoring the control of glucose in patients with Diabetes Mellitus (DM). However, there was difficulty in performing the tests on the patient's samples in the hospital laboratory because the measurement was possible only with gas chromatog-raphy or high performance chromatography. Recently, a reagent that can measure 1,5-AG on the automatic chemistry analyzer was introduced. We evaluated the analytical and clinical characteris-tics of the reagent. METHODS: We measured the 1,5-AG with the Lana(TM) (Japan Chemistry Medicine, Tokyo, Japan) on the automatic chemistry analyzer, TBA-30FR (Toshiba, Otawara, Japan). We evaluated the pre-cision, the recovery rate, the lower detection limit, the reference value, and the correlation with other clinical markers for glucose control of the DM patient. RESULTS: The within-run precisions of abnormal and normal samples were 1.27% and 1.41%. The between-day precisions were 2.34% and 4.56%, respectively. The recovery rate was 100.1% and 100.7% in abnormal and normal samples, respectively. The lower detection limit was 0.05 mg/L. The reference value from the healthy people was from 12.7 to 50.9 mg/L. The correlation coefficients of the 1,5-AG with glucose and HbA1c were -0.45 and -0.63, respectively. CONCLUSIONS: The newly introduced reagent for 1,5-AG that could be applied with the automatic chemistry analyzer was enough to satisfy the analytical features and it showed better correlation with HbA1c than with the fasting blood glucose. We expect that the Lana(TM) can be used in hospital lab-oratories to monitor the blood glucose control of DM patients and more studies on the clinical value of the 1,5-AG can be done with the convenient reagent such as this.