Hyperbilirubinemia in Anicteric Blood? - Clinical Chemistry

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The patient's serum IgG, IgM, and IgA concentrations were 3.9, 0.1, and 39.2 g/L, respectively. Protein elec- trophoresis revealed an IgA- paraprotein (38.3 g/L), ...

Clinical Chemistry 60:11 1457–1462 (2014)

What Is Your Guess?

Hyperbilirubinemia in Anicteric Blood? Yu Chen,1,2* Lauren Graham,3 Ihssan Bouhtiauy,4 Gail Watts,1 and Mary Hamilton1

CASE DESCRIPTION Plasma total bilirubin for a 65-year-old man was high [19.1 mg/dL (326 ␮mol/L)] on a Roche cobas 6000 analyzer. However, the specimen was anicteric and the icteric index was 1 (approximately 1 mg/dL or 17 ␮mol/L). A dilution study demonstrated nonlinear results. Direct bilirubin was measured as normal. The split specimen aliquots were further measured on analyzers from 5 different manufacturers (Table 1). The patient’s total protein and albumin were 93 and 34 g/L (reference intervals: 60 – 80 and 38 –50 g/L).

Table 1. Total bilirubin and direct bilirubin measurements for the 65-year-old man. Total bilirubin, ␮mol/L

Direct bilirubin, ␮mol/L

Roche cobas 6000

326

3

Roche Integra 400

183



Roche Modular P

255

2

Abbott Architect c16000

9

9

Siemens Dimension EXL

5

1

Analyzer

Beckman DxC 600i

11

2

Ortho Vitros 5600

10

9

QUESTIONS 1. What might cause artifactual hyperbilirubinemia in anicteric blood? 2. What strategies can be employed to deal with spurious increased bilirubin results? The answers are below. ANSWERS The patient’s serum IgG, IgM, and IgA concentrations were 3.9, 0.1, and 39.2 g/L, respectively. Protein elec-

trophoresis revealed an IgA-␭ paraprotein (38.3 g/L), a small Bence Jones ␭ in serum, and a prominent Bence Jones ␭ (27.3 g/day) in urine.

1

Department of Laboratory Medicine, Dr. Everett Chalmers Regional Hospital, Horizon Health Network, Fredericton, New Brunswick, Canada; 2 Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada; 3 Department of Laboratory Medicine, Upper River Valley Hospital, Horizon Health Network, Waterville, New Brunswick, Canada; 4 De´partement de Biochimie, Re´seau de sante´ Vitalite´, Edmundston, New Brunswick, Canada. * Address correspondence to this author at: Division of Clinical Biochemistry,

Department of Laboratory Medicine, Dr. Everett Chalmers Regional Hospital, Horizon Health Network, Fredericton, New Brunswick, Canada E3B 5N5. Fax 506-452-5422; e-mail [email protected] Received February 16, 2014; accepted March 26, 2014. DOI: 10.1373/clinchem.2014.223495 © 2014 American Association for Clinical Chemistry

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What Is Your Guess? IgG and IgM paraproteins have been suggested to interfere with total bilirubin assays, especially on Roche analyzers, by forming precipitants (1–5 ). In this case, IgA-␭ and possibly Bence Jones ␭ involvement were indicated. To deal with pseudo-hyperbilirubinemia, naked eye examinations, spectrophotometric indices, different analytical measurements, and the clinical picture will be helpful (1 ).

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

1458 Clinical Chemistry 60:11 (2014)

Authors’ Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.

References 1. Pantanowitz L, Horowitz GL, Upalakalin JN, Beckwith BA. Artifactual hyperbilirubinemia due to paraprotein interference. Arch Pathol Lab Med 2003; 127:55–9. 2. Sheppard CA, Allen RC, Austin GE, Young AN, Ribeiro MA, Fantz CR. Paraprotein interference in automated chemistry analyzers. Clin Chem 2005; 51:1077– 8. 3. Yang Y, Howanitz PJ, Howanitz JH, Gorfajn H, Wong K. Paraproteins are a common cause of interferences with automated chemistry methods. Arch Pathol Lab Med 2008;132:217–23. 4. Cascavilla N, Falcone A, Sanpaolo G, D’Arena G. Increased serum bilirubin level without jaundice in patients with monoclonal gammopathy. Leuk Lymphoma 2009;50:1392– 4. 5. Dutta AK. A curious case of hyperbilirubinemia. Ind J Clin Biochem 2012; 27:200 –1.

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