TOTAL PROT. 6.5 - 8.3 HIGH
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an elevated TOTAL PROTEIN level greater than 8. 3 g/dL. Protein levels are made up of primarily two major portions, the albumin and the globulin fraction. Albumin is covered in another text. Hypergammaglobulinemia is the overproduction of immunoglobulins, and is the entity discussed in this section. As opposed to most other proteins such as albumin, coagulation proteins, ceruloplasmin, and haptoglobin, which are produced in the liver, immunoglobulins are produced by plasma cells. There are five classes of immunoglobulins IgG, IgM, IgE, IgA, and IgD. Each immunoglobulin molecule has two or more basic subunits built of two identical heavy chains and two identical light chains. The light chains are named kappa and lambda and are commonly referred to as the clonal portion of the molecule. On electrophoretic testing, the immunoglobulins migrate to the gamma region. Polyclonal hyperimmunoglobulinemia is a response seen with a wide variety of diseases and is characterized by a wide elevation of the gamma region on serum protein electrophoresis (SPEP). Monoclonal gammopathy refers to a narrow elevation in the gamma region on SPEP which is indicative of a single monoclonal immunoglobulinemia and is associated with a more narrow differential diagnosis to include multiple myeloma, monoclonal gammopathy of undetermined significance, smouldering myeloma, amyloidosis, chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia. While monoclonal gammopathy raises concern over an underlying malignancy or serious condition, polyclonal gammopathy is often viewed as a normal reaction to an underlying condition; however, many of those conditions themselves carry a poor prognosis. Therefore, a thorough evaluation should be performed on each patient to exclude an underlying serious illness when polyclonal gammopathy is detected.
Persistent hyperproteinemia should prompt further evaluation with a serum and urine protein electrophoresis with reflex immunofixation if necessary. Further work-up should be directed based on the abnormality found on the SPEP/UPEP or on the suspicion of an underlying pathologic process. When multiple myeloma is strongly suspected and the SPEP and UPEP are normal (light chain multiple myeloma or nonsecretory myeloma), then further evaluation should include a serum free light chain assay to determine the kappa/lamdba ratio (0.26-1.65) and possibly bone marrow aspiration. Other indications to perform an SPEP/UPEP include unexplained peripheral neuropathy, normocytic anemia associated with an inappropriately low reticulocyte count, hypercalcemia, renal insufficiency, pathologic fractures of the sternum or ribs, unexplained compression fractures, osteoporosis with an abnormal Z score indicative of secondary disease, rouleaux formations noted on blood peripheral smear, and Bence Jones proteinuria.