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.

Two case reports are presented, both illustrating an analytical interference caused by monoclonal immunoglobulins. Falsely low results were obtained in the routine analysis of glucose, CRP and HDL-cholesterol. When analysing samples containing paraproteins, various problems can be encountered in the clinical laboratory: next to the antibody effect, pseudohyponatraemia, hyperviscosity, cryoglobulinaemia and gel formation have to be taken into account. In our two cases the interference was caused by paraprotein precipitation, causing an increased turbidity and an apparent increase of light absorbance at every wavelength due to light scattering, including the wavelengths used in the clinical chemistry assays. We review the literature on this sometimes overlooked interference in photometric/turbidimetric assays. This reaction is based on the insolubility of these proteins in specific physico-chemical circumstances in which many variables are involved, among others: pH and ionic strength, presence of preservatives and surfactants in the assays, pI and other specific properties of the monoclonal immunoglobulins. The complexity of the problem makes predicting or preventing this probably infrequent interference usually impossible. This artifact can cause both false positive and false negative results in multiple parameters (e.g. bilirubin, creatinine, iron, urea, uric acid), the most frequently reported analyte being phosphate. The Sia water test (Sia euglobulin precipitation test) can provide a first clue to a paraprotein aggregation; confirmation can be obtained by observing the time/ absorbance curves of the analysis, performing the test manually or setting up a serial dilution of the sample. The problem can be solved by avoiding the presence of the proteins in the assay, performing the analysis using an alternative method or diluting out the interference. Both laboratorians and clinicians should be aware of interferences in the clinical laboratory since the clinical consequences could be important.