From the Guidelines
The next step in the workup for an elevated protein gap with normal albumin is to order serum protein electrophoresis (SPEP) with immunofixation and serum free light chain assay, as recommended by the NCCN Guidelines for multiple myeloma 1. This combination of tests will help identify the specific proteins causing the gap, particularly monoclonal gammopathies such as multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), or other plasma cell disorders.
- Key points to consider in the workup include:
- Assessing changes and proportions of various proteins, particularly the M-protein, to track disease progression and response to treatment 1
- Using serum free light chain (FLC) assay along with serum protein electrophoresis and serum immunofixation electrophoresis to yield high sensitivity while screening for MM and related plasma cell disorders 1
- Evaluating bone marrow plasma cell infiltration through bone marrow aspiration and biopsy to detect quantitative and/or qualitative abnormalities of bone marrow plasma cells 1
- Considering chromosome analysis by metaphase cytogenetics and fluorescence in situ hybridization (FISH) to identify specific chromosomal abnormalities in patients with MM 1 Additional testing should include complete blood count, comprehensive metabolic panel, calcium levels, and renal function tests to assess for end-organ damage.
- If SPEP reveals a monoclonal protein, bone marrow biopsy may be necessary for definitive diagnosis, and urine protein electrophoresis with immunofixation should also be considered to detect Bence Jones proteins. This approach is recommended because an elevated protein gap (the difference between total protein and albumin) indicates excess globulins in the bloodstream, which can result from chronic inflammation, infection, liver disease, or monoclonal gammopathies, and since albumin is normal, the focus should be on identifying which specific globulin fractions are elevated and determining their clinical significance.
From the Research
Next Steps in Workup for Elevated Protein Gap and Normal Albumin
- The next step in the workup for an elevated protein gap with normal albumin is to perform serum protein electrophoresis (SPEP) to identify and quantify the type of protein present 2, 3.
- SPEP can help differentiate between monoclonal and polyclonal gammopathies, which is essential for further evaluation and management 2.
- If a monoclonal protein is detected, further testing such as immunofixation and free light chain (FLC) assay may be necessary to characterize the protein and assess the risk of progression to multiple myeloma or other related disorders 4, 5.
- The presence of an elevated protein gap with normal albumin may indicate an increased risk of monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM), and patients may require regular monitoring and follow-up to assess for progression 4, 5, 6.
- The use of the protein gap as a screening tool for abnormal serum gammaglobulin levels has been evaluated, and while it may not be a sensitive predictor, it can have a high negative predictive value for monoclonal and polyclonal gammopathy 3.