Dimension Vista® System HIL Technical Bulletin Job Aid

The HIL feature automates the manual process of assessing hemolysis, icterus and lipemia in serum and plasma samples.

Dimension Vista® System Sample Quality Assessment for Hemolysis (H), Icterus (I), Lipemia (L) Technical Bulletin SIEMENS Prepared by Merle B. Smith, MS, MBA Acknowledgments Maryann Szymanski, BS Christopher Seguin, Ph.D Edward Damerau, MS Lucie Fritz, Ph.D Page 1 of 16 D-01498 Version 3.0 Dimension Vista® HIL INTRODUCTION Hemoglobin, bilirubin and lipids have photometric, fluorescence, chemiluminescence and turbidity properties that can cause interference in assays measured by optical techniques in addition to any chemical interference potential they may have. Bilirubin interferes by its absorption and fluorescence properties, hemoglobin by its absorption, fluorescence and chemiluminescence properties, and lipids interfere mostly from their light-scattering (turbidity) properties.1 It has long been recognized that hemolysis, icterus, and lipemia in patient specimens may interfere with accurate spectrophotometric measurement of analytes.2, 3, 4, 5 Identifying specimens with hemolysis, icterus, or lipemia is desirable when laboratories have means to reduce or eliminate some of these preanalytical interferents.6, 7 Inspection of individual specimens by laboratory technologists has been the system for detection and reporting of hemolysis, icterus, and lipemia interference for the past 30 years. Addition of automation to the specimen inspection process can improve HIL detection by introducing standardization and uniformity.7 This technical bulletin describes a Vista® System feature that can report three common preanalytical sample conditions: presence of hemolysis (H), icterus (I), and lipemia (L). The analysis is done by running the HIL request and an index for H, I, L, respectively, is generated for each sample. Each of the sample HIL indices is compared to an alert H, I and L index value corresponding to the concentration of the HIL interferent that has been determined to interfere with a specific method. Table 2 found on page 8 lists the HIL Alert indices for each method and whether the analyte value is decreased or decreased at this level of the interfering substance. HIL configuration, ordering, processing, calculating and reporting on the Dimension Vista® System are described. An internal verification study of HIL indices that was presented at the 2007 AACC meeting will also be included in this bulletin. Additionally, this bulletin provides a brief discussion of the limitations of lipemia interference. Page 2 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL HIL CONFIGURATION ON THE DIMENSION VISTA® SYSTEM There are two types of HIL configuration: global setting and method specific settings. Global Setting The modes are “Off,” “If Needed,” and “Always.” These define when HIL requests are automatically added to the sample order. The mode is configured on the Advanced -> Configuration -> System Config Screen. System Configuration: Semi-Quantitative Results Report the concentration and POS or NEG HIL Configuration Of Off Automatically Print Test Results Always (On) If Needed (Auto On) • The “Off” mode means that the system does not automatically order HIL results. To check the samples, the user must manually order the HIL test on the Manual Order Entry screen or through the LIS. The system will flag methods that have been configured with alert indices when the HIL is manually ordered and if the HIL indices of the sample are equal to or exceed the alert indices for the assay. • “If Needed (Auto On)” mode runs the HIL test on samples only if one or more of the ordered tests have HIL alert indices defined. “If Needed” is the default mode. The system will flag methods that have been configured with alert indices and if the HIL indices of the sample are equal to or exceed the alert indices. • The “Always (On)” mode runs HIL tests on samples irrespective of which methods were ordered. The system will flag methods if they have alert indices in the same way that the system does for the If Needed mode. The system prints HIL indices and sends them to the LIS. Page 3 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL Method Specific Setting Each method has HIL alert index values that apply to both serum and plasma fluid types. By default a method configuration’s alert indices are disabled and no HIL flagging will occur. To activate HIL for particular methods, the user enters alert index values for all methods on which they want HIL checks. The entered value defines the index level that triggers the HIL alert. The HIL alert indices were determined as part of the internal verification testing in R&D using CLSI EP7-A2 Protocol for Interference Testing.8 However, HIL indices may be configured according to the user’s preferences and recommendations by the laboratory director. `HIL Alert Indicies H Threshold: 3 V Enable I Threshold: Enable L Threshold: Enable Table 2 on page 8 provides the recommended alert indices for each method in the presence of HIL interference. HIL interference comments will be generated if the observed HIL values of the sample are greater than or equal to the established alert indices for the method. ORDERING HIL H Interference, I Interference, and L Interference are detected by ordering an HIL test. The three indices are ordered and reported as a set. In “Off” mode, the only way to generate the order is to manually order it. This operation can be done by selecting the HIL method from the Manual Order Entry screen. The HIL request can also be generated by the LIS. When using a DB ASTM protocol, the LIS orders the HIL test with the code 0835. Only one HIL test order is accepted per sample request. More than one HIL cannot be requested on a single sample on the Manual Order Entry screen. Additional HIL requests from the LIS are ignored. In “If Needed” and “Always” mode, the HIL request is not added if there is a manually ordered HIL request. HIL will NOT be automatically added to orders for samples prediluted by the user as indicated by entry of a dilution factor. The user cannot add HIL requests to a sample that has been manually prediluted. If the LIS orders an HIL test on a sample that was manually prediluted, the HIL request is ignored. Page 4 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL HIL PROCESSING and CALCULATION On a Dimension Vista® 1500, HIL tests may use sample probes 1, 2 or 3, or the IMT probe for sample delivery to the cuvette. The probe to be used is determined at the time that the test is scheduled so as to maximize use of the instrument's resources and to maintain throughput. The sample probe or the IMT probe delivers 10 µL of sample fluid with 15 µL of chase (system water) to a cuvette containing 150 µL of system water. On a Dimension Vista® 500, scheduling of HIL tests has no effect on throughput. The IMT probe delivers the sample to an odd-numbered cuvette, which is not routinely used on a Dimension Vista® 500. For the purpose of scheduling, HIL is a low sensitivity test and will normally be run out of the low sensitivity aliquot. However, if there is insufficient sample in the low sensitivity aliquot, a high sensitivity aliquot may be used (if sufficient volume exists). The ‘H’ absorbance is read at 405 and 700 nm; the ‘I’ at 452 and 700 nm and the ‘L’ absorbance is derived from a blanked 700 nm measurement. The absorbance measurements for H, I, L are converted to HIL indices that correspond to approximate concentrations of hemoglobin, bilirubin and lipemia as shown in Table 1. An index of 1 represents concentrations of the interferences not affecting the analytical performance of the method. Table 1 ‘H’ ‘I’ ‘L’ Index Hemoglobin Bilirubin Intralipid (mg/dL) (mg/dL) (mg/dL) 1 H ≤ 10 I ≤ 2 L ≤ 50 2 10 < H ≤ 25 2 < I ≤ 5 50 < L ≤ 100 3 25 < H ≤ 50 5 < I ≤ 10 100 < L ≤ 200 4 50 < H ≤ 200 10 < I ≤ 15 200 < L ≤ 400 5 200 < H ≤ 300 15 < I ≤ 20 400 < L ≤ 600 6 300 < H ≤ 500 20 < I ≤ 40 600 < L ≤ 800 7 500 < H ≤ 1,000 40 < I ≤ 60 800 < L ≤ 1,000 8 H > 1,000 I > 60 L > 1,000 The following charts depict a qualitative representation of varying degrees of hemolysis, icterus and lipemia spiked in a serum pool and the corresponding HIL indices. Page 5 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL Serum pool spiked with varying amounts of hemoglobin HB 10 18 25 38 50 100 150 200 250 3.00 40 0 500 6 00 1000 1200 HB nde: 2 2 2 3 4 4 4 5 8 - Serum pool spiked with varying amounts of bilirubin 3 LI o 1 2 6 10 16 F.6 20 40 50 60 70 Index 2 18 2 2 4 4 OBS) Serum pool spiked with varying amounts of lipemia (Intralipid®) 25 50 75 100 150 300 300 400 500 600 700 800 900 1000 1200 TRIC 55 107 169 221 294 384 516 631 706 786 985 > 1000 > 1000 > 1000 LIP 2 2 3 3 5 8 Intralipid® is a registered trademark of Fresenius Kabi AG, Bad Homburg, Germany. DETERMINATION OF HIL ALERT VALUES Every assay on the Dimension Vista® System has been tested for HIL interference according to the CLSI/NCCLS Evaluation Protocol EP7-A2.8 Serum pools were spiked with varying amounts of hemoglobin, bilirubin and lipemia (Intralipid®). These spiked samples along with a negative serum pool (no interfering substance) were analyzed for each method on the Dimension Vista® system. Bias was determined as the difference in the results between the control Page 6 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL sample (without the interferent) and the test sample (contains the interferent) expressed in percent. Bias exceeding 10% is considered interference. Alert Indices (threshold levels) defined as the smallest concentration of HIL that would interfere (yielding a bias greater than 10%) with the analyte results have been established and can be configured to trigger an interference flag next to the analyte result. HIL indices range from low (1) to high (8). The laboratory has the option of entering HIL indices based on the laboratory policies with considerations on acceptable medical decision errors, impact on clinical interpretations and ability to mitigate preanalytical specimen interfering substances. The Dimension Vista® System minimizes HIL interferences based on the methodologies utilized on the instrument. LOCI® Methods Dimension Vista® LOCI® methods are homogeneous chemiluminescence immunoassays. These methods minimize chemical and spectral interference potential from HIL substances where possible by use of very small sample sizes and background chemiluminescence subtraction. Turbidimetric Methods Dimension Vista® turbidimetric methods reduce HIL interference where possible by use of sample blank subtraction. Nephelometric Methods Turbidity and particles in the samples may interfere with the determination. Therefore, samples containing particles must be centrifuged prior to testing. Lipemic or turbid samples, which cannot be clarified by centrifugation (10 minutes at approximately 15,000 x g) must not be used. IMT Methods Indirect ion-selective methodologies as employed by Dimension VLyte® sensors can underreport electrolyte concentrations when an extreme amount of lipemia is present in a sample. Accurate electrolyte results on such samples can be achieved if the lipid fraction is removed before electrolytes are measured. Table 2 is a list of methods and the HIL alert indices indicating the presence of HIL interference. The effect of HIL interference is shown as an increase (pink highlight) or decrease (light green highlight) in analyte value. Methods that are not affected by HIL are designated by “N/A”. Page 7 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL Table 2 (N/A = No interference) Ledenct dece ases ICE as es METHOD H ME THOD H L 1 A1AG N/A N/A 53 hsCRP N/A N/A N/A 2 A1AT NA N/A N/A 54 IGA N/A N/A 3 A1MIC N/A N/A 55 IGE N/A N/A 4 ACTM NA 2 N/A 56 IGG1 NIA N/A N/A 5 AFP N/A N/A 57 IGG2 N/A N/A SALB N/A N/A 58 IGG3 N/A N/A N/A 7 ALP NAA N/A N/A 59 IGG4 N/A N/A 8 ALT NAA 7 4 60 IGG N/A N/A 9 APOA1 N/A N/A 61 IGM N/A N/A 10 APOB N/A N/A 62 IRON 3 N/A N/A 11 AMON 8 63 K 3 (b) N/A 12 AMY 7 N/A 8 64 LA 7 13 ASL N/A N/A 65 LDH 3 (0) N/A 7 14 AST 7 4 66 LDI 3 (b) N/A N/A 15 B12 NAA N/A N/A 67 LDLC NIA 7 8 16 B2MIC N/A N/A N/A 8 |LI N/A N/A N/A 17 BHCG N/A 69 LIDO N/A 7 18 BUN N/A 70 LIPL N/A N/A NIA 19 C1IN NA N/A N/A 71 MALB N/A N/A 20 C4 N/A N/A 72 MBI 2 6 5 21 CA NA N/A 5 73 MG 3 (b N/A N/A 22 CEA NAA N/A N/A 23 CER 74 MMB 7 N/A NA. N/A N/A 75 MYO N/A 24 CHOL 3 8 76 NA N/A N/A 25 CK 7 N/A 77 NAPA N/A N/A 26 CKI 4 8 78 PBNP N/A 2 8 79 PBNP-MONOCLONAL N/A 27 CKMB 2 N/A N/A 28 CL N/A NIA 80 PCHE NA N/A N/A 29 C02 N/A 81 PHNO N/A NIA 30 CRBM N/A 82 PHOS 7 7 5 31 CREA 4 N/A 83 PREALB NA N/A NIA 32 CRP NIA N/A 84 PROC NA N/A 8 33 CSA NA NIA N/A 85 PTN N/A 8 34 CSAE N/A N/A 86 RBP N/A N/A NIA 35 CTNI 7 N/A NIA 7 RF N/A NIA 36 CYSC NA N/A N/A 88 SAL 2 7 PRESET IN METHPAR 37 DBL N/A 8 89 STFR N/A N/A 38 DGTX N/A N/A 90 T3 NA N/A N/A 39 DIG 7 6 91 T4 N/A 8 40 ETOH N/A N/A 92 TBIL NA N/A 41 FERR N/A N/A 93 THEO NIA N/A 8 42 FOL N/A 94 TIBC 4 N/A 7 43 FT3 6 N/A 95 TOBR N/A N/A 44 FT4 7 6 96 TP NA 6 8 45 GENT N/A 97 TRF N/A N/A 46 GGT 7 N/A 98 TRIG 3 NIA 47 GLU N/A 99 TSH N/A N/A 48 HA1C N/A NIA 100 TU N/A N/A 49 HAPT N/A N/A 101 UCFP NIA N/A N/A 50 HDLC N/A 8 N/A N/A 51 HCYS 102 URCA N/A 52 HPX NIA N/A 103 VALP NIA N/A N/A 104 VANC N/A NIA NIA NIA a) The Dimension Vista® will annotate a DBIL result with a comment “Hemoglobin Interference” for a sample with a hemoglobin concentration of 50 mg/dL or greater equivalent to an H index of “3 to 8”. Page 8 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL b) An alert index of “3” equivalent to 25-50 mg/dL of hemoglobin is configured for these analytes that have increased intracellular concentrations. HIL REPORTING • If the H, I, or L level is below the alert index (threshold level) for the method, the method result is reported without an HIL interference flag. • If the H, I, or L level is equal to or greater than the alert index the result is reported with the appropriate H, I, or L comment indicating potential interference. • The HIL comments are: “H Interference,” “I Interference,” and “L Interference.” On the LIS, DBASTM codes are: E111, E113, E191, respectively. The HIL results are reported on routine and advanced screens, on printouts, and through the LIS data stream. The comments associated with other tests because of high HIL indices are also reported in these ways. The HIL results appear as follows on the routine screen. All Samples >> Results Patient Name: lian Sample ID: Patient ID: 2342 04234 Samples Sample Fluid Type: sample Priority: e Sampled Time: e priority Sample List Instrument ID: SE 7-1213:31:15 INCADUS Method Result Units Range Flags Comments Rack / Aliquot BUN 0.350 moral 7 - 18 action FOAM Data Injected Raw Readings, Results Below Reference H ndex Range, H Interference Demographics index Data Injected Raw Readings Add-On Tests 8 index Data Injected Raw Readings Print Rerun All Tests Cancel Selected Tests All Samples STAT Samples - Problem Samples Manual Order Entry Sample Rack Detail Setup Patient Samples System When the Vista® System is running and the result is flagged, the sample is added to the problem sample list. An example of this is shown below: Page 9 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL User: Dade Behring System Standby roblom Samples 16:02:51 Serum Methods Panels Problem Samples Methods Service ACTM ACTM2c ALB ALC Sample ID Problem Rack Position Priority Resolution Other Action ALP AL ALTW AMY 0712042342 Flagged with HIL AA111111-1 ROUTINE Dismiss Show Rack AST BNP BUN C3 C4 CA CK CKMB CL CRBM CREA CRP CTNI DBI DIG ECO2 ERR FOL FPSA GENT GLU HCG HDL HIL CRP IGA IGM IRN Methods Print Page Up Page Dowr IIjj amples Racks Help All Samples STAT Samples · Problem Samples Manual Order Entry Sample Rack Detail Favorites Methods Guide Setup Patient Samples System Reporting HIL Indices Each HIL index is listed separately as seen in the following reports. Vista® Report Siemens Technical Support Laboratory Name: Patient ID: 5678 Gender. U Sample ID: 1234 Sample Type:SERUM Dilution Factor: 1 Priority: Routine Rack Position: BZ000314-1 Completed On: 2009-03-20 Operator: Siemens Instrument ID: 11330051 Started On: 2009-03-20 Comment: Method Result Units RefRange Flag Comment Reagent H index index - 1 index RON 106 ug/dL 50.0 - 175.0 08266AC TIBC 274 ug/dl 250.0 - 450.0 08273AC AST 19 U/L 15.0 - 37.0 08281AA EASYLINK™ Result Manager Report Patient ID: Date of Birth: Last Name: Sex: U First Name: Sample 1234 S mL Aspartate Aminotransferase 19 UL Iran null Total Iron Binding Capacity 274 ug'dL Hemolysis Index nul 2 index Icterus Index null 1 index Lipemia Index null 1 index LIS Report Page 10 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL Each index is reported separately to the LIS. The following is a snippet of ASTM protocol that shows HIL results being reported to the LIS. H|\^&|1||Instrument|||||HOST|||DB 100102|20050713102417| P|1||432100101||Potter^Lillian^^||00010101||||||^^^^||||||||||\||^|||||||||| O|1|123402034||^^^2816^2202^Hemolysis\^^^2817^2202^Icterus\^^^2818^2202^Lipemia\^^^2101^2202^Blood Urea Nitrogen|R||||||N||||S^|^^^^||1|4|||20050713102417|||F||||| R|1|^^^2816^2202^Hemolysis|6|index||||F|||20050713094640|20050713094807|GGSEGUINCADUS R|2|^^^2817^2202^Icterus|1|index||||F|||20050713094640|20050713094807|GGSEGUINCADUS R|3|^^^2818^2202^Lipemia|8|index||||F|||20050713094640|20050713094807|GGSEGUINCADUS R|4|^^^2101^2202^Blood Urea Nitrogen||||||F|||20050713095052|20050713095356|GGSEGUINCADUS C|1|I|E121^Never Calibrated|E C|2|I|E111^H Interference|E C|3|I|R001^2101051640090112233XX|R C|4|I|R002^20050911000000|R C|5|I|R003^000005|R L|1|N C|6|I|Z001^-1.16079480216216|Z Process Error Handling If a process error occurs while processing an HIL request, the HIL request is retried. If it encounters a second error, the HIL request will report the process error. No H, I, or L interference comments will be produced for the other tests with potential interferences. If the user wants the HIL comments, the entire sample must be rerun. LIMITATIONS OF LIPEMIA INTERFERENCE TESTING The most prevalent cause for lipemia is an increase in triglyceride concentration in plasma and serum. This can be due to food intake, an altered lipid metabolism or to infusion of lipids. After enteral absorption, plasma triglycerides are present in the circulation as chylomicrons and their metabolic products (remnants) for 6 to 12 h. In lipemia, chylomicrons and VLDL are suspended particles that scatter light, producing cloudiness or turbidity similar to that seen in milk.9 Chylomicrons represent a heterogeneous group of particles ranging in size from 70 to 1000 nm and varying greatly in size distribution and number among individuals. Because VLDL and chylomicron particles vary greatly in size and triglyceride content, one might expect that a direct measure of triglycerides would not show good correlation with light scattering.10 Several factors should be considered when examining the influence of lipemia on analytical methods. Lipemia can be simulated using a 10 or 20 % fat emulsion as applied in parenteral nutrition (e.g. Intralipid®). However, one must exercise care in interpreting observations using artificially produced lipemia that may not be transferable to the biological condition due to the differences between the effects of “physiological” and the artificially produced lipemia.11 Unfortunately, there is no uniform human lipid standard available. Lipemia indices for the Dimension Vista® System were based on studies using Intralipid®, a fat emulsion spiked into human serum pools and measured at 700 nm. Intralipid® is a registered trademark of Fresenius Kabi AG, Bad Homburg, Page 11 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL Germany. IntraLipid® is different from VLDL and chylomicrons. It is a sterile, nonpyrogenic fat emulsion for intravenous infusion containing, per liter, 200 mL of soybean oil, 12 mL of egg yolk phospholipids, and 22 mL of glycerin with the balance made up by water. The particles range in size from 200 to 600 nm with a mean of 345 nm.12 Samples with added Intralipid® do not perfectly mimic lipemic samples. The heterogeneous nature of lipemia creates difficulties in simulating samples. Both VLDL and chylomicrons effectively scatter light, causing turbidity. IntraLipid® completely misses the range of values for large VLDL and misses the lower and upper ranges for chylomicrons. Furthermore, the refractive index of IntraLipid® is near 1.47 and differs from those of lipoproteins.12 High levels of lipemia can variably decrease transmission due to light scattering and the heterogeneity of endogenous lipid species prevents measured triglycerides levels in the specimens to correlate with visual lipemia or the lipemia index (L). Unlike hemolysis or icterus, the interference caused by lipemia can be reduced by removal of the interfering lipid. For best results, lipemic specimens should be cleared of visible lipemia. Several methods have been proposed, such as ultracentrifugation, filtration, and solvent extraction. A refrigerated sample and/or centrifuge would make the separation of chylomicrons from the sample easier but would not reduce the VLDL fraction. VERIFICATION OF ASSIGNED HIL INDICES Our Technical Support Laboratory (TSL) has verified the accuracy of the HIL indices generated on samples at specific HIL concentrations. Known concentrations of hemoglobin, bilirubin and lipemia (Intralipid®) were spiked into serum pools and analyzed for HIL. Table 3A verifies the agreement between the observed HIL indices and the concentrations of hemoglobin, bilirubin and lipemia. Table 3B references the Dimension Vista® HIL indices and the corresponding concentrations of hemoglobin, bilirubin and lipemia (Intralipid®). Table 3A Page 12 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL Hemoglobin Observed Bilirubin Observed Lipemia (Intralipid) Sample (mg/dL) H Index mg/dL I Index mg/dL 1 10 1 1 1 25 2 18 2 2 2 50 3 50 3 3.5 2 75 4 150 4 7.5 3 100 5 200 4 10 3 200 6 250 5 15 4 300 7 300 5 20 5 400 8 500 6 30 6 800 9 600 7 50 7 1000 10 1000 7 70 8 1500 Table 3B ‘H’ ‘I’ ‘L’ Index Hemoglobin Bilirubin Intralipid (mg/dL) (mg/dL) (mg/dL) 1 H ≤ 10 I ≤ 2 L ≤ 50 2 10 < H ≤ 25 2 < I ≤ 5 50 < L ≤ 100 3 25 < H ≤ 50 5 < I ≤ 10 100 < L ≤ 200 4 50 < H ≤ 200 10 < I ≤ 15 200 < L ≤ 400 5 200 < H ≤ 300 15 < I ≤ 20 400 < L ≤ 600 6 300 < H ≤ 500 20 < I ≤ 40 600 < L ≤ 800 7 500 < H ≤ 1,000 40 < I ≤ 60 800 < L ≤ 1,000 8 H > 1,000 I > 60 L > 1,000 VERIFICATION OF HIL COMMENTS Additionally, our TSL laboratory has verified that HIL interference comments are generated on samples that have HIL indices equal to or greater than the configured alert indices. Table 4 shows the HIL configuration for AST, CA, CHOL, CK, CKMB, DBIL, GLU, TP and TRIG on the Dimension Vista® System. No HIL index is configured for a method that does not get interfered by HIL. Samples with HIL indices equal to or greater than these alert indices will generate HIL Interference comments. Table 4 Page 13 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL “H” “I “ “L” Alert Index Alert Index Alert Index Method AST 3 7 4 CA No interference No interference 5 CK 7 No interference 8 CKMB 2 2 5 CHOL 3 8 DBIL 4 No interference 8 GLU No interference No interference 3 TP No interference No interference 6 TRIG No interference 3 No interference Table 5 shows the HIL interference comments generated on 25 serum samples with HIL indices that are equal to or greater than the Alert indices for AST, CA, CHOL, CK, CKMB, DBIL, GLU, TP and TRIG. The normal samples (n=3) with HIL indices of 1-1-1 did not generate HIL interference comments as to be expected. Table 5 # of Samples Reported Sample Quality tested HIL Indices Methods flagged with HIL Comments 3 1_1_1 No Interference Comments generated 2 1_2_1 I Interference (CKMB) 2 1_3_1 I Inteference CKMB, CHOL, TRIG) 2 2_3_1 H Interference, I Interference (CKMB), I Interference(CHOL, TRIG) 1 3_1_2 H Interference (AST, CKMB, DBIL) 1 3_1_3 H Interference (AST, CKMB) , L Interference (GLU) 3 3_3_1 H Interference (AST, CKMB), I Interference (CHOL, CKMB, TRIG) 1 3_3_2 H Interference (AST, CKMB), I Interference(CHOL, CKMB, TRIG) 5 4_1_1 H Interference (AST, CKMB, DBIL) 1 4_1_2 H Interference (AST, CKMB, DBIL) 2 4_2_1 H Interference (AST, CKMB, DBIL); I Interference (CKMB) 1 4_3_3 H Interference (AST, CKMB, DBIL); I Interference (CKMB, CHOL, TRIG) 1 5_1_5 H Interference ( (AST, CKMB, DBIL); L Interference (AST, CA, CKMB, GLU) 1 5_2_1 H Interference ( (AST, CKMB, DBIL),I Interference (CKMB) 1 6_4_4 H Interference ( (AST,CKMB, DBIL); I Interference (CKMB, CHOL, TRIG); L Interference (AST, GLU) 1 7_2_1 H Interference ((AST, CHOL, DBIL), I Interference(CKMB) Additional HIL testing performed on 36 serum samples generated HIL indices that were below the alert indices for ALP, ALT, CREA, MG, PHOS, TBIL, URCA. Therefore, as expected, no HIL comments were generated on these samples. Page 14 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL CONCLUSIONS The functionality and accuracy of the automated HIL feature have been successfully verified on the new Dimension Vista® System. This method specific, customizable approach provides sample quality assurance and standardization of result reporting. The Dimension Vista® System’s ability to provide HIL detection without additional consumables or reagents effectively identifies preanalytical sample errors, thereby enhancing accuracy in data interpretation, eliminating added costs and post analytical delays. The HIL feature results in improved individual sample turnaround time and uncompromised system throughput. Page 15 of 16 D-01498 06/11/2009 Version 3.0 Dimension Vista® HIL BIBLIOGRAPHY 1. Dasgupta A. ed. Handbook of Drug Monitoring Methods: Therapeutics and Drugs of Abuse. Totowa NJ. Humana Press, 2008: pp 97-109 nd 2. Henry RJ, Cannon DC, Winkelman JW, eds. Clinical chemistry, 2 ed. Hagerstown, Harper and Row, 1974:P. 41. 3. Meites S. Reproducibly simulating hemolysis for evaluating interference with chemical methods [Letter]. Clin chem 1973;19:1319. 4. Sage GW, LeFever S, Henry JB. Evaluation of the revised serum calcium procedure used with the DuPont automatic clinical analyzer. Clin Chem 1975;21:850-2. 5. Grafmeyer D, Bondon M, Manchon M, Levillain P. The influence of bilirubin, haemolysis, and turbidity on 20 analytical tests performed on automated analyzers. Eur J Clin Chem Clin Biochem 1995;33:31-52. 6. Glick MR, Ryder KW, Glick SJ, Woods, JR. Unreliable visual estimation of the incidence and amount of turbidity, hemolysis, and icterus in serum from hospitalized patients. Clin Chem 1989;35:837. 7. MLO Website: 8. Clinical and Laboratory Standards Institute/NCCLS. Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition. CLSI/NCCLS document EP7-A2 [ISBN 1-56238-584-4]. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898 USA, 2005. 9. Kroll MH, Elin RJ. Interference with clinical laboratory analyses. Clin Chem 1994;40:1996-2005 10. Park Y, Grellner, Harris WS, Miles JM. A new method for the study of chylomicron kinetics in vivo. Am J Physiol Endocrinol Metab 2000;279:E1258-E1263 11. Sonntag O, Glick MR. Serum-Index und interferogramm—Ein neuer Weg zur Prufung und Darstellung von Interferenzen durch Serumchromogene. Lab Med 1989;13:77-82.) 12. Wabel C. Influence of lecithin on structure and stability of parenteral fat emulsions. (Doctoral thesis July 30, 1998 Den Naturwissenschaftlichen Fakultaten der Friedrich-Alexander-Universitat Erlangen Nurnberg.) Page 16 of 16 D-01498 06/11/2009 Version 3.0