CME Topic

Artifactual Laboratory Abnormalities in Patients with Paraproteinemia

Authors: Vivek Roy MD

Abstract

Abstract:Paraproteinemia, most often as a result of monoclonal gammopathy of unknown significance (MGUS), is very common and its prevalence is expected to increase with the aging of the population. Paraproteins can be associated with a variety of laboratory abnormalities. These may occur as a result of the underlying disease process that causes paraproteinemia, or may result from the paraproteins affecting a physiologic function in vivo. Laboratory abnormalities may also occur artifactually as a result of interference by the paraproteins with a laboratory test in vitro. A wide variety of laboratory tests may be affected, including several commonly obtained tests such as blood counts, serum sodium, calcium, phosphorous, and high-density lipoprotein (HDL) cholesterol. There is poor correlation between the concentration or type of paraproteins and the likelihood of interference. Awareness of this possibility is important so as to avoid erroneous diagnostic conclusions or unnecessary testing.

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References

References1. Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 2006;354:1362–1369.KyleRA]]TherneauTM]]RajkumarSV&etal;Prevalence of monoclonal gammopathy of undetermined significance.N Engl J Med20063541362-13692. Iwanaga M, Tagawa M, Tsukasaki K, et al. Prevalence of monoclonal gammopathy of undetermined significance: study of 52,802 persons in Nagasaki City, Japan. Mayo Clin Proc 2007;82:1474–1479.IwanagaM]]TagawaM]]TsukasakiK&etal;Prevalence of monoclonal gammopathy of undetermined significance: study of 52,802 persons in Nagasaki City, Japan.Mayo Clin Proc2007821474-14793. Landgren O, Katzmann JA, Hsing AW, et al. Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana. Mayo Clin Proc 2007;82:1468–1473.LandgrenO]]KatzmannJA]]HsingAW&etal;Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana.Mayo Clin Proc2007821468-14734. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43–66.JemalA]]SiegelR]]WardE&etal;Cancer statistics, 2007.CA Cancer J Clin20075743-665. Groves FD, Travis LB, Devesa SS, et al. Waldenstrom’s macroglobulinemia: incidence patterns in the United States, 1988–1994. Cancer 1998;82:1078–1081.GrovesFD]]TravisLB]]DevesaSS&etal;Waldenstrom’s macroglobulinemia: incidence patterns in the United States, 1988–1994.Cancer1998821078-10816. Sheppard CA, Allen RC, Austin GE, et al. Paraprotein interference in automated chemistry analyzers. Clin Chem 2005;51:1077–1078.SheppardCA]]AllenRC]]AustinGE&etal;Paraprotein interference in automated chemistry analyzers.Clin Chem2005511077-10787. Bowles SA, Tait RC, Jefferson SG, et al. Characteristics of monoclonal immunoglobulins that interfere with serum inorganic phosphate measurement. Ann Clin Biochem 1994;31(pt 3):249–254.BowlesSA]]TaitRC]]JeffersonSG&etal;Characteristics of monoclonal immunoglobulins that interfere with serum inorganic phosphate measurement.Ann Clin Biochem199431pt 3249-2548. Sonnenblick M, Eylath U, Brisk R, et al. Paraprotein interference with colorimetry of phosphate in serum of some patients with multiple myeloma. Clin Chem 1986;32:1537–1539.SonnenblickM]]EylathU]]BriskR&etal;Paraprotein interference with colorimetry of phosphate in serum of some patients with multiple myeloma.Clin Chem1986321537-15399. Yamada K, Yagihashi A, Ishii S, et al. Interference with nephelometric assay of C-reactive protein and antistreptolysin-O by monoclonal IgM-kappa from a myeloma patient. Clin Chem 1997;43:2435–2437.YamadaK]]YagihashiA]]IshiiS&etal;Interference with nephelometric assay of C-reactive protein and antistreptolysin-O by monoclonal IgM-kappa from a myeloma patient.Clin Chem1997432435-243710. Merlini G, Farhangi M, Osserman EF. Monoclonal immunoglobulins with antibody activity in myeloma, macroglobulinemia and related plasma cell dyscrasias. Semin Oncol 1986;13:350–365.MerliniG]]FarhangiM]]OssermanEFMonoclonal immunoglobulins with antibody activity in myeloma, macroglobulinemia and related plasma cell dyscrasias.Semin Oncol198613350-36511. Shoenfeld Y, el-Roeiy A, Ben-Yehuda O, et al. Detection of anti-histone activity in sera of patients with monoclonal gammopathies. Clin Immunol Immunopathol 1987;42:250–258.ShoenfeldY]]el-RoeiyA]]Ben-YehudaO&etal;Detection of anti-histone activity in sera of patients with monoclonal gammopathies.Clin Immunol Immunopathol198742250-25812. Waldenstrom JG. Antibody activity of monoclonal immunoglobulins in myeloma, macroglobulinemia and benign gammapathy. Med Oncol Tumor Pharmacother 1986;3:135–140.WaldenstromJGAntibody activity of monoclonal immunoglobulins in myeloma, macroglobulinemia and benign gammapathy.Med Oncol Tumor Pharmacother19863135-14013. Robert F, Mignucci M, McCurdy SA, et al. Hemostatic abnormalities associated with monoclonal gammopathies. Am J Med Sci 1993;306:359–366.RobertF]]MignucciM]]McCurdySA&etal;Hemostatic abnormalities associated with monoclonal gammopathies.Am J Med Sci1993306359-36614. Spicka I, Rihova Z, Kvasnicka J, et al. Disturbances of anticoagulation and fibrinolytic systems in monoclonal gammopathies-another mechanism of M-protein interference with hemostasis. Thromb Res 2003;112:297–300.SpickaI]]RihovaZ]]KvasnickaJ&etal;Disturbances of anticoagulation and fibrinolytic systems in monoclonal gammopathies-another mechanism of M-protein interference with hemostasis.Thromb Res2003112297-30015. Haeney MR. Erroneous values for the total white cell count and ESR in patients with cryoglobulinaemia. J Clin Pathol 1976;29:894–897.HaeneyMRErroneous values for the total white cell count and ESR in patients with cryoglobulinaemia.J Clin Pathol197629894-89716. Roberts WL, Fontenot JD, Lehman CM. Overestimation of hemoglobin in a patient with an IgA-kappa monoclonal gammopathy. Arch Pathol Lab Med 2000;124:616–618.RobertsWL]]FontenotJD]]LehmanCMOverestimation of hemoglobin in a patient with an IgA-kappa monoclonal gammopathy.Arch Pathol Lab Med2000124616-61817. Gumprecht T, O’Connor DT, Rearden A, et al. Negative anion gap in a young adult with multiple myeloma. Clin Chem 1976;22:1920–1921.GumprechtT]]O’ConnorDT]]ReardenA&etal;Negative anion gap in a young adult with multiple myeloma.Clin Chem1976221920-192118. Valdivieso A, Costa M, Robino X, et al. [Pseudohyponatremia and anion gap changes in multiple myeloma]. Rev Med Chil 1989;116:559–562.ValdiviesoA]]CostaM]]RobinoX&etal;[Pseudohyponatremia and anion gap changes in multiple myeloma].Rev Med Chil1989116559-56219. Vaswani SK, Sprague R. Pseudohyponatremia in multiple myeloma. South Med J 1993;86:251–252.VaswaniSK]]SpragueRPseudohyponatremia in multiple myeloma.South Med J199386251-25220. Sachs J, Fredman B. The hyponatramia of multiple myeloma is true and not pseudohyponatramia. Med Hypotheses 2006;67:839–840.SachsJ]]FredmanBThe hyponatramia of multiple myeloma is true and not pseudohyponatramia.Med Hypotheses200667839-84021. Adler SG, Laidlaw SA, Lubran MM, et al. Hyperglobulinemia may spuriously elevate measured serum inorganic phosphate levels. Am J Kidney Dis 1988;11:260–263.AdlerSG]]LaidlawSA]]LubranMM&etal;Hyperglobulinemia may spuriously elevate measured serum inorganic phosphate levels.Am J Kidney Dis198811260-26322. Mandry JM, Posner MR, Tucci JR, et al. Hyperphosphatemia in multiple myeloma due to a phosphate-binding immunoglobulin. Cancer 1991;68:1092–1094.MandryJM]]PosnerMR]]TucciJR&etal;Hyperphosphatemia in multiple myeloma due to a phosphate-binding immunoglobulin.Cancer1991681092-109423. Oren S, Feldman A, Turkot S, et al. Hyperphosphatemia in multiple myeloma. Ann Hematol 1994;69:41–43.OrenS]]FeldmanA]]TurkotS&etal;Hyperphosphatemia in multiple myeloma.Ann Hematol19946941-4324. Sinclair D, Smith H, Woodhead P. Spurious hyperphosphataemia caused by an IgA paraprotein: a topic revisited. Ann Clin Biochem 2004;41(pt 2):119–124.SinclairD]]SmithH]]WoodheadPSpurious hyperphosphataemia caused by an IgA paraprotein: a topic revisited.Ann Clin Biochem200441pt 2119-12425. McClure D, Lai LC, Cornell C. Pseudohyperphosphataemia in patients with multiple myeloma. J Clin Pathol 1992;45:731–732.McClureD]]LaiLC]]CornellCPseudohyperphosphataemia in patients with multiple myeloma.J Clin Pathol199245731-73226. Kiki I, Gundogdu M, Kaya H. Spuriously high phosphate level which is promptly resolved after plasmapheresis in a patient with multiple myeloma. Transfus Apher Sci 2007;37:157–159.KikiI]]GundogduM]]KayaHSpuriously high phosphate level which is promptly resolved after plasmapheresis in a patient with multiple myeloma.Transfus Apher Sci200737157-15927. Pierce GF, Garrett NC, Koenig J, et al. Interference by monoclonal proteins in the o-phthalaldehyde method for blood urea nitrogen. Clin Chim Acta 1986;154:233–236.PierceGF]]GarrettNC]]KoenigJ&etal;Interference by monoclonal proteins in the o-phthalaldehyde method for blood urea nitrogen.Clin Chim Acta1986154233-23628. Smith JD, Nobiletti J, Freed M, et al. Interference with the Astra 8 and Synchron CX3 assays of urea nitrogen in serum by a high-M(r) inhibitor in a patient with multiple myeloma. Clin Chem 1992;38:598–599.SmithJD]]NobilettiJ]]FreedM&etal;Interference with the Astra 8 and Synchron CX3 assays of urea nitrogen in serum by a high-M(r) inhibitor in a patient with multiple myeloma.Clin Chem199238598-59929. Datta P, Graham GA, Schoen I. Interference by IgG paraproteins in the Jaffe method for creatinine determination. Am J Clin Pathol 1986;85:463–468.DattaP]]GrahamGA]]SchoenIInterference by IgG paraproteins in the Jaffe method for creatinine determination.Am J Clin Pathol198685463-46830. Pantanowitz L, Horowitz GL, Upalakalin JN, et al. Artifactual hyperbilirubinemia due to paraprotein interference. Arch Pathol Lab Med 2003;127:55–59.PantanowitzL]]HorowitzGL]]UpalakalinJN&etal;Artifactual hyperbilirubinemia due to paraprotein interference.Arch Pathol Lab Med200312755-5931. Nauti A, Barassi A, Merlini G, et al. Paraprotein interference in an assay of conjugated bilirubin. Clin Chem 2005;51:1076–1077.NautiA]]BarassiA]]MerliniG&etal;Paraprotein interference in an assay of conjugated bilirubin.Clin Chem2005511076-107732. John R, Oleesky D, Issa B, et al. Pseudohypercalcaemia in two patients with IgM paraproteinaemia. Ann Clin Biochem 1997;34(pt 6):694–696.JohnR]]OleeskyD]]IssaB&etal;Pseudohypercalcaemia in two patients with IgM paraproteinaemia.Ann Clin Biochem199734pt 6694-69633. Bakker AJ. Influence of monoclonal immunoglobulins in direct determinations of iron in serum. Clin Chem 1991;37:690–694.BakkerAJInfluence of monoclonal immunoglobulins in direct determinations of iron in serum.Clin Chem199137690-69434. Hachem H, Favre G, Ghalim N, et al. Quantitative abnormalities of lipoprotein particles in multiple myeloma. J Clin Chem Clin Biochem 1987;25:675–679.HachemH]]FavreG]]GhalimN&etal;Quantitative abnormalities of lipoprotein particles in multiple myeloma.J Clin Chem Clin Biochem198725675-67935. Baca A, Haber RJ, Sujishi K, et al. Artifactual undetectable HDL-cholesterol with the Beckman synchron LX and vitros 950 assays temporally associated with a paraprotein. Clin Chem 2004;50:255–256.BacaA]]HaberRJ]]SujishiK&etal;Artifactual undetectable HDL-cholesterol with the Beckman synchron LX and vitros 950 assays temporally associated with a paraprotein.Clin Chem200450255-25636. Tsai LY, Tsai SM, Lee SC, et al. Falsely low LDL-cholesterol concentrations and artifactual undetectable HDL-cholesterol measured by direct methods in a patient with monoclonal paraprotein. Clin Chim Acta 2005;358:192–195.TsaiLY]]TsaiSM]]LeeSC&etal;Falsely low LDL-cholesterol concentrations and artifactual undetectable HDL-cholesterol measured by direct methods in a patient with monoclonal paraprotein.Clin Chim Acta2005358192-19537. Kadri N, Douville P, Lachance P. Monoclonal paraprotein may interfere with the Roche direct HDL-C Plus assay. Clin Chem 2002;48(6 pt 1):964.KadriN]]DouvilleP]]LachancePMonoclonal paraprotein may interfere with the Roche direct HDL-C Plus assay.Clin Chem2002486 pt 196438. Yang Y, Howanitz PJ, Howanitz JH, et al. Paraproteins are a common cause of interferences with automated chemistry methods. Arch Pathol Lab Med 2008;132:217–223.YangY]]HowanitzPJ]]HowanitzJH&etal;Paraproteins are a common cause of interferences with automated chemistry methods.Arch Pathol Lab Med2008132217-22339. Berth M, Delanghe J. Protein precipitation as a possible important pitfall in the clinical chemistry analysis of blood samples containing monoclonal immunoglobulins: 2 case reports and a review of the literature. Acta Clin Belg 2004;59:263–273.BerthM]]DelangheJProtein precipitation as a possible important pitfall in the clinical chemistry analysis of blood samples containing monoclonal immunoglobulins: 2 case reports and a review of the literature.Acta Clin Belg200459263-273