Abstract
The influence of interference by hemolysis, icterus and lipemia on the results of routine chemistries may lead to wrong interpretations. On Synchron LX-20 instruments (Beckman Coulter) serum or plasma indices can be used as reliable semi-quantitative measures of the magnitude of such interference. In an article recently published in this journal, we presented the results of a multicenter study carried out in Dutch hospitals in which we determined cutoff indices for analytes above which analytically significant interference exists. Clinically significant interference cutoff indices were also derived for these analytes. In this article, we describe the handling of patient samples with clinically significant interference by hemolysis, icterus or lipemia. We investigated several possible approaches for correction of the result: dilution of the interference; mathematical correction in the case of hemolysis; treatment with ferrocyanide to destroy bilirubin; and removal of lipids in lipemic patient samples. We concluded, that mathematical correction of potassium or lactate dehydrogenase results in hemolytic samples can only be carried out if intravascular hemolysis is ruled out. Hemoglobin quantification in serial patient samples, combined with measurement of haptoglobin, represents a useful tool to rule out in vivo hemolysis. We derived an algorithm for this situation. We do not simply recommend mathematical correction, unless it is clinically acceptable. We present formulas for potassium and lactate dehydrogenase: corrected potassium=measured potassium–(hemolytic index increment×0.14); corrected lactate dehydrogenase=measured lactate dehydrogenase–(hemolytic index increment×75). The dilution studies indicated that dilution is only applicable for bilirubin, C-reactive protein and iron. The results of treatment with ferrocyanide were poor, and we do not recommend this method. Removal of lipids using high-speed centrifugation or LipoClear (StatSpin Inc.), a non-toxic and non-ionic polymer, is a very effective approach, although C-reactive protein, creatine kinase-MB (CK-MB) and cholesterol cannot be removed using LipoClear. For all interferants (hemoglobin, bilirubin, lipids), relatively simple algorithms are derived that can easily be implemented in the clinical laboratory.
Clin Chem Lab Med 2007;45:114–9.
References
1. Young DS. Effect of drugs on clinical laboratory tests. Washington, DC: AACC, 1990.Search in Google Scholar
2. Andall AG, Garcia-Webb P, Beilby JP. Interference by haemolysis, icterus and lipaemia in assays on the Beckman Synchron CX5 and methods for correction. Ann Clin Biochem1990;27:345–52.10.1177/000456329002700411Search in Google Scholar PubMed
3. Steen G, Vermeer HJ, Naus AJ, Goevaerts B, Agricola PT, Schoenmakers CH. Multicenter evaluation of the interference of hemoglobin, bilirubin and lipids on Synchron LX-20 assays. Clin Chem lab Med2006;44:413–9.10.1515/CCLM.2006.067Search in Google Scholar PubMed
4. Kroll MH, Elin RJ. Interferences with clinical laboratory analyses. Clin Chem1994;40:1996–2005.10.1093/clinchem/40.11.1996Search in Google Scholar
5. Sheppard CA, Allen RC, Austin GE, Young AN, Ribeiro MA, Fantz CR. Paraprotein interference in automated chemistry analyzers. Clin Chem2005;51:1077–8.10.1373/clinchem.2004.045740Search in Google Scholar PubMed
6. Behrendt H. Chemistry of erythrocytes. Springfield, IL: Charles C Thomas, 1957.Search in Google Scholar
7. Caraway WT. Chemical and diagnostic specificity of laboratory tests. Am J Clin Pathol1962;37:445–64.10.1093/ajcp/37.5.445Search in Google Scholar PubMed
8. Sonntag O, Glick MR. Serum-Index und Interferogramm – ein neuer Weg zur Prüfung und Darstellung von Interferenzen durch Serumchromogene. Lab Med1989;13:77–81.10.1515/labm.1989.13.3.77Search in Google Scholar
9. Schoenmakers CH, Kuller T, Lindemans J, Blijenberg BG. Automated enzymatic methods for creatinine measurement with special attention to bilirubin interference. Eur J Clin Chem Clin Biochem1993;31:861–8.10.1515/cclm.1993.31.12.861Search in Google Scholar PubMed
10. Spain MA, Wu AH. Bilirubin interference with determination of uric acid, cholesterol, and triglycerides in commercial peroxidase-coupled assays, and the effect of ferrocyanide. Clin Chem1986;32:518–21.10.1093/clinchem/32.3.518Search in Google Scholar
11. Lippi G, Salvagno, GL, Montagnana M, Brocco G, Guidi GC. Influence of hemolysis on routine clinical chemistry testing. Clin Chem Lab Med2006;44:311–6.10.1515/CCLM.2006.054Search in Google Scholar PubMed
12. Ismail A, Shingler W, Seneviratne J, Burrows G. In vitro and in vivo haemolysis and potassium measurement. Br Med J2005;330:949.10.1136/bmj.330.7497.949Search in Google Scholar PubMed PubMed Central
13. Jay DW, Provasek D. Characterization and mathematical correction of hemolysis interference in selected Hitachi 717 assays. Clin Chem1993;39:1804–10.10.1093/clinchem/39.9.1804Search in Google Scholar
14. Dimeski G, Clague AE, Hickman PE. Correction and reporting of potassium results in haemolysed samples. Ann Clin Biochem2005;42:119–23.10.1258/0004563053492739Search in Google Scholar PubMed
15. Hawkins R. Variability in potassium/hemoglobin ratios for hemolysis correction [letter]. Clin Chem2002;48:796.10.1093/clinchem/48.5.796Search in Google Scholar
16. Manoharan A. Congenital haptoglobin deficiency. Blood1997;90:170910.1182/blood.V90.4.1709aSearch in Google Scholar
17. Vassault A, Grafmeyer D, Naudin C, Dumont G, Bailly M, Henny J, et al. Protocol for the validation of methods. Document B, stage 3. Commission for validation of methods of the Société Francaise de Biologie Clinique. Ann Biol Clin1986;44:686–745.Search in Google Scholar
18. Westgard JO. Desirable specifications for total error, imprecision, and bias, derived from biologic variation. http://www.westgard.com/biodatabase1.htm.Search in Google Scholar
19. Sigurdsson G. Enteral or parenteral nutrition? Proenteral Acta Anaesthesiol Scand Suppl1997;110:143–7.10.1111/j.1399-6576.1997.tb05537.xSearch in Google Scholar PubMed
20. Chong PH, Bachenheimer BS. Current, new and future treatments in dyslipidaemia and atherosclerosis. Drugs2000;60:55–93.10.2165/00003495-200060010-00005Search in Google Scholar PubMed
21. Bornhorst JA, Roberts RF, Roberts WL. Assay-specific differences in lipemic interference in native and Intralipid-supplemented samples. Clin Chem2004;50:2197–201.10.1373/clinchem.2004.040154Search in Google Scholar PubMed
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