Hae-il Park

Effects of total cholesterol and triglyceride on the percentage difference between the low-density lipoprotein cholesterol concentration measured directly and calculated using the Friedewald formula.

Abstract Background: We elucidate how the triglyceride (TG) and total cholesterol (TC) concentrations affect the percentage difference (%ΔLDL) between the low-density lipoprotein cholesterol (LDL-C) concentration evaluated by direct measurement (DLDL-C) and calculated using the Friedewald formula (FLDL-C), under conditions allowing the calculation. Methods: Serum concentrations of TC, TG, high-density lipoprotein cholesterol (HDL-C), and DLDL-C were measured and the FLDL-C and %ΔLDL were calculated for 38,243 Koreans who had TG values <4.52 mmol/L. The DLDL-C was measured using the homogeneous Kyowa Medex assay (Kyowa, Tokyo, Japan). The %ΔLDL was calculated using the equation: [(FLDL-C–DLDL-C)/DLDL-C]×100. Results: The mean %ΔLDL-C was –9.1±6.4%. The %ΔLDL differed by more than ±5% in 75.4% of the subjects, and the FLDL-C was lower than the DLDL-C in 96.3%. The mean %ΔLDL-C for the group with the highest TG and lowest TC was 11.8-fold that for the group with the lowest TG and highest TC. Conclusions: Under conditions satisfying the requirements of the Friedewald formula, the DLDL-C and FLDL-C differed significantly over the concentration ranges of both TC and TG. In an evaluation of patients with hyperlipidemia, the Friedewald calculation may underestimate the risk for coronary heart disease. Clin Chem Lab Med 2008;46:371–5.

Glycated albumin may be a possible alternative to hemoglobin A1c in diabetic patients with anemia.

Abstract Background: We assessed whether glycated albumin (GA) is a useful glycemic indicator in diabetic patients with anemia who did not undergo dialysis. Methods: Hemoglobin A1c (HbA1c) and GA were simultaneously measured in 370 diabetic subjects who had not undergone dialysis. The relationship between GA and HbA1c was evaluated in patients with and without anemia. Results: GA-to-HbA1c ratio was significantly higher (3.3±0.7 vs. 2.8±0.5, p<0.001) and the regression slope between GA and HbA1c was steeper in diabetic patients with than in those without anemia (6.2 vs. 4.2, p<0.001). Conclusions: HbA1c was underestimated in diabetic patients with anemia than in those without anemia, with the degree of underestimation increasing as glycemic control became poorer. GA may more accurately assess glycemic control in diabetic patients with anemia than HbA1c.

Two distinct clonal populations in acute promyelocytic leukemia, one involving chromosome 17 and the other involving an isochromosome 17.

Acute promyelocytic leukemia (APL) is characterized by a t(15;17)(q22;q21) rearrangement. Additional chromosomal rearrangements have been reported in 25-40% of APL patients. The most common abnormality involving chromosome 17 is ider(17). Here we report the case of a patient with APL with isochromosome 17q combined with ider(17), confirmed by fluorescence in situ hybridization. Cytogenetic data strongly suggest that the involvement of chromosomes 15 and 17 in translocation occurs after formation of the isochromosome 17. The case reported here presents the novel finding of two separate clonal events apparently occurring at the same time in an APL patient.

Performance Evaluation of Affinity Column Mediated Immunometric Assay for Tacrolimus

BACKGROUND Therapeutic drug monitoring (TDM) of tacrolimus is essential because of narrow therapeutic range and poor correlation of dose to blood concentration. Affinity Column Mediated Immunometric Assay (ACMIA) does not require a pretreatment steps in measurement of tacrolimus. In this study, we evaluated the performance of tacrolimus assay using ACMIA (Dimension RxL Max, Dade Behring). METHODS The imprecision, the linearity and the detection limits and the interferences by bilirubin and chyle, and correlation with hematocrit for tacrolimus by ACMIA were evaluated according to Clinical and Laboratory Standards Institute guidelines EP5-A2, EP6-A, EP17-A, EP9-A2, and EP7-A2. Method comparison studies with microparticle enzyme immunoassay (MEIA) (IMx Tacrolimus II, Abbott Laboratories) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) (Waters 2795 Quattromicro API, Micromass) were also performed. RESULTS The total imprecision for low, middle and high level was 12.8%, 9.0% and 6.7%, respectively. The range of tacrolimus from 3.1 ng/mL to 35.4 ng/mL showed a clinically relevant linearity. The limit of detection and the functional sensitivity were 0.24 ng/mL and 0.72 ng/mL, respectively. Tacrolimus concentration measurement (Tac-CM) with ACMIA did not show significant interferences with bile and chyle and also did not show significant correlation with hematocrit. In comparison study for Tac-CM with MEIA and LC-MS/MS, Tac-CM with ACMIA showed a good correlation with MEIA (r=0.950) and LC-MS/MS (r=0.946). CONCLUSIONS The imprecision, linearity, detection limits, interference and correlation of Tac-CM with ACMIA were suitable for clinical use. Tac-CM with ACMIA could reduce turn around time and help clinicians to manage transplant patients on immunosuppressant therapy.

Genetic–pathologic characterization of myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more myeloid lineages. The current study demonstrates that three driver mutations were detected in 82.6% of 407 MPNs with a mutation distribution of JAK2 in 275 (67.6%), CALR in 55 (13.5%) and MPL in 6 (1.5%). The mutations were mutually exclusive in principle except in one patient with both CALR and MPL mutations. The driver mutation directed the pathologic features of MPNs, including lineage hyperplasia, laboratory findings and clinical presentation. JAK2-mutated MPN showed erythroid, granulocytic and/or megakaryocytic hyperplasia whereas CALR- and MPL-mutated MPNs displayed granulocytic and/or megakaryocytic hyperplasia. The lineage hyperplasia was closely associated with a higher mutant allele burden and peripheral cytosis. These findings corroborated that the lineage hyperplasia consisted of clonal proliferation of each hematopoietic lineage acquiring driver mutations. Our study has also demonstrated that bone marrow (BM) fibrosis was associated with disease progression. Patients with overt fibrosis (grade ⩾2) presented an increased mutant allele burden (P<0.001), an increase in chromosomal abnormalities (P<0.001) and a poor prognosis (P<0.001). Moreover, among patients with overt fibrosis, all patients with wild-type JAK2/CALR/MPL (triple-negative) showed genomic alterations by genome-wide microarray study and revealed the poorest overall survival, followed by JAK2-mutated MPNs. The genetic–pathologic characteristics provided the information for understanding disease pathogenesis and the progression of MPNs. The prognostic significance of the driver mutation and BM fibrosis suggests the necessity of a prospective therapeutic strategy to improve the clinical outcome.

Analytical performance of a new one-step quantitative prostate-specific antigen assay, the FREND™ PSA Plus

Abstract Background: We evaluated the analytical performance of a new one-step rapid quantitative sandwich immunoassay for total prostate-specific antigen (tPSA), the FREND™ PSA Plus (FREND PSA) (NanoEnTek Inc., Seoul, Korea). Methods: The imprecision, linearity, hook effect, detection limit (LoD), and interference were evaluated and trueness verification and matrix validation were performed. For method comparison, 79 patient specimens were analyzed with FREND PSA and two comparative tPSA assays (Architect® total PSA and cobas® total PSA assay). Results: Total CVs of the imprecision for low (0.208 ng/mL), medium (4.051 ng/mL), and high PSA levels (5.469 ng/mL) were 15.9%, 6.4%, and 9.1%, respectively. Linearity was observed from 1.01 to 19.15 ng/mL and the hook phenomenon was absent up to 171.48 ng/mL. The LoD was 0.094 ng/mL. The regression equations between FREND (y) and Architect or cobas were as follows: y=0.0133+1.054x (r=0.973), y=–0.2144+1.066x (r=0.977), respectively. Differences between FREND PSA and the comparative methods at a medical decision level of 4.0 ng/mL were less than the optimum specification bias (9.3%). The percentage biases from the trueness verification and interference test were less than the desirable specifications for bias (18.7%). The plasma tPSA level measured with lithium heparin or K2EDTA was comparable to that in the serum. Conclusions: The FREND PSA provided reliable analytical performance and test results in comparison to two widely used tPSA assays. It is a simple and rapid test for tPSA and can be applied in point-of-care testing.

Quantitative detection of target cells using unghosted cells (UGCs) of DxH 800 (Beckman Coulter).

Abstract Background: In the Retic channel of DxH 800 (Beckman Coulter), the red blood cells (RBCs) resistant to hemoglobin clearing are counted as unghosted cells (UGCs). The aim of this study was to evaluate that the UGC is a surrogate marker for both the detection and counting of target cells. Methods: In total, 1181 samples including 22 from iron deficiency anemia (IDA) patients, 95 from jaundice, 2 from sickle cell anemia, 3 from thalassemia, 1 cord blood, and 269 from normal controls were analyzed. Slides were prepared from all samples except normal controls and target cells were counted for correlation analysis of target cell counts to UGCs. Results: The normal control samples showed 0.01% (0%–0.01%) UGCs, and the reference range was set at ≤0.02%. The IDA samples showed 0.015% (0.01%–0.03%) UGC count and 0.05% (0%–0.2%) target cell count. The jaundice samples showed 0.98% (0.1%–5.36%) UGC count, and 1.4% (0.1%–7.0%) target cell count. The two sickle cell anemia samples showed 0.41% and 3.74% UGC counts and 0.4% and 11.5% target cell counts. A cord blood sample showed 0.01% UGCs and 0% target cells. The three thalassemia samples showed 0.01%, 1.99%, and 7.82% UGC counts and 0%, 1.4%, and 15.5% target cell counts. The samples showing poikilocytosis other than target cells showed normal UGC count (≤0.02%). The positive predictive value of UGCs was 58.2% (124/213) and the negative predictive value was 96.8% (674/696). The UGC counts were well correlated to the manual target cell counts (r=0.944, p=0.000). Conclusions: This study demonstrates for the first time in the literature that a hematological parameter obtained automatically every time a reticulocyte counting is performed can be used to both screen for the presence of target cells and reliably quantify them.

Performance Characteristics of Glycated Albumin and Its Clinical Usefulness in Diabetic Patients on Hemodialysis

BACKGROUND The HbA1c has been considered to underestimate glucose level in diabetic patients on hemodialysis, therefore, glycated albumin (GA) was recently introduced to assess the glycemic control for those cases. We evaluated the performance of GA assay kit of Lucica GA-L (Asahi Kasei Pharma Co., Japan) and compare it with HbA1c for estimating glucose levels. METHODS Tests for precision, linearity and interference were performed and reference interval was determined. Thirty eight of non-hemodialysis and seventy of hemodialysis patients were recruited, whose glucose levels of three-, two- and one-month prior to this study were available for calculating weighted means of glucose (WMGs). The correlation coefficients and the slopes of regression equation between WMG and HbA1c or GA were compared between two groups. Multiple linear regression analyses were used to determine significant predictor for HbA1c and GA. RESULTS Total CV was 2.2% at concentration of 13.7% and 2.8% at 24.6%. The dilution curve between 15.7% and 62.1% was linear. Reference intervals were 10.0% to 16.5% for male and 11.4% to 17.6% for female. The correlation coefficients between WMG and GA were 0.682-0.713 in hemodialysis and 0.640-0.677 in non-hemodialysis. Those between WMG and HbA1c were 0.568-0.625 in hemodialysis and 0.735-0.783 in non-hemodialysis. The slopes of regression equation between GA and WMG in hemodialysis were 0.080-0.090 and 0.130-0.147 in non-hemodialysis. Those between HbA1c and WMG in hemodialysis were 0.012-0.014 and 0.029-0.032 in non-hemodialysis. GA was not influenced by hemodialysis status while HbA1c was. CONCLUSIONS The claimed performance characteristic of Lucica GA-L were verified. WMG were better reflected by GA rather than HbA1c in patients on hemodialysis.

Effectiveness of Sodium Fluoride as a Glycolysis Inhibitor on Blood Glucose Measurement: Comparison of Blood Glucose using Specimens from the Korea National Health and Nutrition Examination Survey

BACKGROUND Accurate measurement of blood glucose concentrations is essential for defining diabetes, and the minimization of ex vivo glycolysis has been recommended. Recent guidelines advocate two kinds of methods for sample collection and processing: either the sodium fluoride (NaF) method or immediate refrigeration using a serum separation tube (SST). We investigated the difference between the two methods in measuring subsequent glucose concentrations using blood specimens from participants recruited for the fourth Korean National Health and Nutrition Examination Survey. METHODS Paired venous blood samples were collected in an SST and a NaF tube from 1,103 men and women. SST serum was separated within 30 min, including standing for 15 min, and then refrigerated. The NaF samples were refrigerated, but not separated until immediately before analysis. We compared the blood glucose concentrations between the SST (SST glucose) and NaF (NaF glucose) methods. RESULTS The mean SST glucose was significantly higher than NaF glucose (99.0 mg/dL vs 96.5 mg/dL, P<0.05). NaF glucose showed a negative mean bias of 2.6 mg/dL vs SST glucose but showed high correlation (R=0.9899). There was no significant correlation between the bias of blood glucose concentrations by two methods and the storage time of NaF glucose. CONCLUSIONS The negative bias associated with the use of NaF tubes may significantly affect the prevalence of diabetes. Serum separation and refrigeration within 30 min after venous sampling is recommended over NaF method, not only to minimize the preanalytical impact on detecting diabetes but also to reduce sample volume and number of tubes.

Sigma-Metrics of Electrolyte Tests From a Recently Launched New-Generation Proficiency Testing Program of the Korean Association of Quality Assurance for Clinical Laboratory

Hee Jin Huh, M.D.*, Yun Mi Park, M.D.*, Seungok Lee, M.D., Chunhwa Ihm, M.D., Soyeon Seo, M.D., Sang Gon Lee, M.D., Joonseok Park, M.D., and Hae-il Park, M.D. Department of Laboratory Medicine, Dongguk University Ilsan Hospital, Goyang; Siemens Healthineers, Seoul; Department of Laboratory Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Incheon; Department of Laboratory Medicine, School of Medicine, Eulji University, Daejeon; Samkwang Medical Laboratories, Seoul; Green Cross Laboratories, Yongin; Hanmi Medicare Inc., Seoul; Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea