Pseudohyperphosphataemia in patients with multiple myeloma.

McClure, D; Lai, Leslie C.; Cornell, Christopher

doi:10.1136/jcp.45.8.731

Cited by 20 publications

(10 citation statements)

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“…In previous reports where a series of patient samples was investigated, different criteria for pseudohyperphosphataemia were used, 6,9,11,12 and this may explain the variable incidence (8-49%) of this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Paraprotein Interference Causing Pseudohyperphosphataemia: Evaluation of an Improved Methodology

Savory

Pearce

1995

Ann Clin Biochem

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SUMMARY. The measurement of serum inorganic phosphorus by direct acidl molybdate assay is known to be subject to interference by some serum paraproteins. Serum samples from 45 paraproteinaemic patients were used for the measurement of inorganic phosphorus using a manufacturer's kit reagent and a detergent-modified reagent from the same manufacturer. In addition, the same samples were analysed with both reagents following precipitation of serum protein with trichloroacetic acid. Using the original reagent pseudohyperphosphataemia was found in 27ftJo (12/45) of the samples. The modified reagent was free from interference with no significant difference between results from serum and protein-free supernatants. Additional key phrases: acid molybdate inorganic phosphorusPseudohyperphosphataemia has been reported previously in patients with paraproteins. Some studies have shown that interference is due to turbidity caused by precipitation of the paraprotein by the acid reagent used in both visible and ultra-violet spectrophotometric methods.l:'! Other workers have identified the presence of a phosphate binding immunoglobulin.P:"! The Boehringer Mannheim (BM UK Ltd, Sussex, UK) method for inorganic phosphorus (Product No. 1040898) is known to be subject to interference in some patients with paraproteins." The manufacturer's claim that interference has been reduced significantly by a recent change in reagent composition.We have compared the performance of the two reagent kits in samples from 45 patients with paraproteinaemia using whole serum and proteinfree supernatants of the same serum. MATERIALS AND METHODSBlood samples from 45 patients in whom paraproteins had previously been identified by electrophoresis and typing by immunofixation were obtained for diagnosis or treatment monitoring.Correspondence: D J Savory. 498The study included samples with IgG (n = 36, range 8-80 giL), IgA (n = 5, range 11-28 giL) and IgM (n = 4, range 10-33 giL) paraproteins. Aliquots of serum were stored at -20°C prior to analysis.Serum inorganic phosphorus was measured on an Hitachi 717 using two kits (BM Cat No. 1040898) of different lot numbers. Kit X (Lot No. 645386) was the original formulation, and Kit Y (Lot No. 650415) contained the modified reagent. Serum was diluted with sulphuric acid and the blank absorbance measured at 340 nm and 376 nm. On addition of ammonium molybdate, inorganic phosphorus is converted to ammonium phosphomolybdate which is measured at 340 and 376 nm. The final concentrations were: molybdate 1·0 mmol/L, sulphuric acid 0·35 mol/L, sodium chloride 44 mmol/L and detergent. Kits X and Y differed in detergent composition, the details of which have not been disclosed by the manufacturers.The same serum samples were analysed using both reagents after precipitation of protein using equal volumes of serum and 0·61 mol/L trichloracetic acid, the method currently in use in this laboratory when hyperphosphataemia is found in patients with paraproteins. The supernatant was analysed directly following centrifugation.Inorg...

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Section: Discussionmentioning

confidence: 99%

Paraprotein Interference Causing Pseudohyperphosphataemia: Evaluation of an Improved Methodology

Savory

Pearce

1995

Ann Clin Biochem

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“…The formation of the complex is pH dependent and uses an acid buffer (3,7 ). The low pH environment of the reaction mixture can lead to precipitation of immunoglobulins and result in increased turbidity and light scattering (5,7 ). Resolution of the interference is obtained by diluting the sample or removing the plasma proteins via various deproteinization methods (5, 7 ).…”

Section: Immunoglobulin Excess Affecting Measurement Of Phosphorousmentioning

confidence: 99%

“…Absorbance of the unreduced phosphomolybdate complex is measured and indexed to a calibration curve to determine analyte concentration (3,7 ). The formation of the complex is pH dependent and uses an acid buffer (3,7 ). The low pH environment of the reaction mixture can lead to precipitation of immunoglobulins and result in increased turbidity and light scattering (5,7 ).…”

Section: Immunoglobulin Excess Affecting Measurement Of Phosphorousmentioning

confidence: 99%

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Unexpected Test Results in a Patient with Multiple Myeloma

Gilbert

Bachmann

2014

Clinical Chemistry

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A 53-year-old male patient with an established diagnosis of IgG multiple myeloma was seen by a hematologistoncologist in consultation from an outside hospital. He had previously received 1 cycle of chemotherapy treatment, but he was found to be intermittently noncompliant with his therapy. The patient reported occasional nosebleeds and fatigue. Except for a slightly cachectic appearance, the physical examination was unremarkable. Laboratory results are shown in Table 1.Serum protein electrophoresis revealed monoclonal paraproteinemia in high abundance marked by an intense band in the ␥ region. Immunofixation electrophoresis was not ordered at that time, but it was previously performed at another institution and was positive for IgG monoclonal protein.The attending pathologist noted the discrepancy between the presence of a monoclonal band by serum protein electrophoresis and the patient's quantitative immunoglobulin measurements. Several additional suspicious test results were also noted. DISCUSSIONMultiple myeloma is a hematologic malignancy characterized by proliferation of a neoplastic plasma cell population that usually leads to abundant production of a monoclonal immunoglobulin, also called paraprotein or M-protein, as well as decreased concentrations of normal polyclonal immunoglobulins. Overwhelming expansion of plasma cells in the bone marrow with concomitant suppression of other normal blood cell lineages often results in thrombocytopenia and anemia, which are classically manifested as symptoms of bleeding and fatigue. Renal insufficiency, as evidenced by increased blood creatinine and blood urea nitrogen concentrations, also may occur and is likely due to filtration of associated monoclonal free light chains, which can cause tubular damage. Serum protein electrophoresis typically yields a discrete band in the ␥ region, and immunofixation demonstrates the presence of IgG monoclonal protein in over 50% of cases (1 ).Overproduction of plasma proteins in concentrations that exceed typical physiologic limits can be an important source of laboratory test interference. Paraproteins can adversely affect various instruments and methodologies. For example, a paraproteinassociated increase in blood viscosity can cause difficulty in sample aspiration by some instruments that results in assessments being performed on smaller-than-expected sample volumes and subsequent falsely decreased laboratory results (2 ). In addition, M-proteins, especially those that are also cryoglobulins, can precipitate and cause erroneous measurements via several methods (1 ). Other interferences such as the prozone effect and the volume displacement effect are discussed below. IMMUNOGLOBULIN EXCESS AND THE PROZONE EFFECTQuantitative immunoglobulin concentrations in this case were suspiciously low considering the marked increases in total protein, the large monoclonal band identified on serum electrophoresis, and the patient's anemia and thrombocytopenia, all of which suggested the presence of active disease.Immunoglobulins IgA, IgM, and ...

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“…or by the removal of protein, either by pretreatment of the samples or by using an analyser which incorporates a dialysis step. 3,5,7,8,[10][11][12] Correspondence: Dr Shirley A Bowles. examination of the reaction mixture in a number of studies has indicated that significant turbidity occurs in some cases of paraproteinaemia.s-v'I-P The precipitates produced in this way have been shown to contain the monoclonal immunoglobulin present in the unprocessed serum.…”

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confidence: 99%

Characteristics of Monoclonal Immunoglobulins That Interfere with Serum Inorganic Phosphate Measurement

Bowles

Tait

Jefferson³

et al. 1994

Ann Clin Biochem

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SUMMARY. The measurement of inorganic phosphate using an unmodified acid/molybdate assay is known to be subject to interference when paraproteinaemia exists. This phenomenon, due to precipitation in the reaction mixture, is not common to all paraproteins. We studied sera from 35 patients to determine whether interference in the assay was related to particular electrophysical characteristics of the paraproteins. There were spuriously elevated phosphate concentrations in 48' 6070 of the sera assayed. This could not be related to a direct effect of light chain type, electrical charge or IgO subclass. No IgA paraproteins were found to cause interference but there were immunoglobulin 0 (lgO) and immunoglobulin M (lgM) paraproteins in both the 'interfering' and 'non-interfering' groups. The median paraprotein concentration was similar in both groups but, where interference occurred, the degree increased in line with the paraprotein concentration. Although it does not seem possible to predict which samples will cause interference, it is important that the clinical implications of this problem are appreciated.

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Pseudohyperphosphataemia in patients with multiple myeloma.

Cited by 20 publications

References 4 publications

Paraprotein Interference Causing Pseudohyperphosphataemia: Evaluation of an Improved Methodology

Paraprotein Interference Causing Pseudohyperphosphataemia: Evaluation of an Improved Methodology

Unexpected Test Results in a Patient with Multiple Myeloma

Characteristics of Monoclonal Immunoglobulins That Interfere with Serum Inorganic Phosphate Measurement

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