MonashPathology MonashHealth HYPERALBUMINAEMIA – SEVERE DEHYDRATION OR ASSAY INTERFERENCE? Kay Weng Choy1, James CG Doery1,2, Nilika Wijeratne1,2,3 1Monash Pathology, Monash Medical Centre; 2Department of Medicine, Monash University; Clayton, Vic. 3168; 3Dorevitch Pathology, Heidelberg, Vic. 3084 kay.choy@monashhealth.org The most routinely used automated albumin methods are the dye-binding bromocresol purple (BCP) and bromocresol green (BCP). However, capillary zone electrophoresis (CZE) is more accurate and reliable (1). The AACB Working Party of Standardised Reporting of Protein Electrophoresis has recommended that both albumin and total protein plus globulin calculations be performed for older patients as part of routine liver function tests to facilitate early recognition of a paraprotein disorder (1) and that laboratories investigate major discrepancies between the chemical and electrophoretic albumin results. Paraproteins are known to interfere with laboratory assays including albumin. Negative interference by paraprotein in the BCG albumin method has previously been reported (2). We report a case of paraprotein interference in the BCP albumin method. CASE A 78 year old female with lymphoplasmacytic lymphoma had a serum albumin of 71 g/L by BCP method (Beckman AU5800) even though she was not clinically dehydrated. Her total protein, albumin, calculated globulin and paraprotein results over last few months are shown in Table 1 and Figure 1. DISCUSSION (continued) Falsely higher albumin results would have resulted in an erroneously low corrected calcium in this patient If globulin is used for early recognition of a paraprotein disorder, falsely calculated globulin may occur due to wrong albumin result. Albumin is one of two parameters used in the international staging system (ISS) to determine multiple myeloma prognosis and to stratify patients in numerous trials worldwide (3); wrong albumin results may put patients into wrong prognostic groups. 23/2/15 14/5/15 9/6/15 3/9/15 9/11/15 Total protein (biuret method, Beckman DxC800) (g/L) 97 105 101 Beckman AU 5800) (g/L) 116 Albumin (BCP, Beckman DxC 800) (g/L) 56 64 59 61 71 Calculated globulin (g/L) 41 40 45 Monoclonal type/mass on AGE IgG k 48 g/L 50 g/L 58 g/L Table 1. Patient’s total protein, BCP albumin and IgG kappa (IgG k) monoclonal mass concentrations over one-year period RESULTS The most recent albumin result was re-checked using four different methods with widely discrepant results (Table 2). Agarose gel (AGE) & CZE scans of the patient’s serum gave similar results. (Figures 2 and 3) Figure 1. Patient’s BCP albumin and IgG kappa monoclonal mass concentrations over one-year period Albumin methods Albumin results BCP albumin (Beckman AU 5800) 71 g/L BCG albumin (Siemens Advia) 35 g/L AGE (Sebia Hydrasys) 30 g/L CZE (Sebia Capillarys) DISCUSSION The BCP albumin result was likely wrong given that the more specific methods such as CZE agreed with BCG albumin and the albumin to globulin (A/G) ratio was surprisingly >1 in context of the patient’s disease (Table 1). The albumin appeared to rise and fall with paraprotein concentrations, suggestive of proportional paraprotein interference in BCP method (Figure 1 and Table 1). There is lack of literature data regarding paraprotein interference in BCP albumin measurement. Significant clinical consequences may occur as a result of wrong albumin results. CONCLUSION Clinicians and pathologists must be aware of paraprotein interference in both BCG and BCP albumin assays. Discrepancies between chemical and electrophoretic albumin results should raise the possibility of paraprotein interference. Table 2. Patient serum albumin measured by different methods Figure 2. Agarose gel electrophoresis (AGE) of patient serum Total protein (biuret method): 116 g/L Albumin (AGE): 30 g/L; Paraprotein: IgG kappa 58 g/L REFERENCES Tate J et al. Recommendations for standardized reporting of protein electrophoresis in Australia and New Zealand. Ann Clin Biochem 49( ):242-256 King RI, Florkowski CM. How paraprotein can affect laboratory assays: spurious results and biological effects. Pathology 42(5):397-401 Palumbo A et al, Revised international staging system for multiple myeloma: a report from international myeloma working group. http://jco.ascopubs.org/content/early/2015/08/03/JCO.2015.61.2267.short Figure 3. Capillary zone electrophoresis (CZE) of patient serum Total protein (biuret method): 116 g/L Albumin (CZE): 35 g/L ; Paraprotein: IgG kappa 53 g/L