Causes of Elevated Total Serum Protein at 87 g/L
A total serum protein of 87 g/L represents hyperproteinemia, which is most commonly caused by dehydration/hemoconcentration or monoclonal gammopathies (particularly multiple myeloma), and requires immediate evaluation with serum protein electrophoresis and immunofixation to distinguish between these etiologies.
Primary Diagnostic Approach
The evaluation must begin with determining whether this represents a polyclonal or monoclonal increase in proteins 1:
Immediate Laboratory Workup Required
- Serum protein electrophoresis (SPEP) with immunofixation - essential to identify monoclonal proteins that appear as homogeneous spike-like peaks in the gamma-globulin zone 2, 1
- Serum free light chain assay - complements electrophoresis for detecting light chain disorders 2
- Complete blood count with differential - assess for plasma cells, rouleaux formation 2
- Serum albumin measurement - helps calculate albumin/globulin ratio and assess protein distribution 2
Major Causes of Hyperproteinemia
1. Hemoconcentration/Dehydration (Most Common)
- Volume depletion causes relative increase in all protein fractions proportionally 1
- Look for: elevated hematocrit, increased BUN/creatinine ratio, clinical signs of dehydration
- This is a polyclonal pattern on electrophoresis 1
2. Monoclonal Gammopathies (Most Serious)
Multiple myeloma is the primary concern with this level of elevation 2, 1:
- Requires: clonal bone marrow plasma cells ≥10%, serum/urinary monoclonal protein present, and end-organ damage (hypercalcemia, renal insufficiency, anemia, bone lesions) 2
- Serum monoclonal protein ≥3 g/dL supports diagnosis 2
- Homogeneous spike on SPEP is pathognomonic 1
Other monoclonal causes include 1:
- Monoclonal gammopathy of undetermined significance (MGUS)
- Waldenström's macroglobulinemia
- Smoldering multiple myeloma
- Plasma cell leukemia
- Primary amyloidosis
3. Chronic Inflammatory/Infectious Conditions (Polyclonal Pattern)
These cause polyclonal hypergammaglobulinemia 1:
- Chronic liver disease (cirrhosis) - though typically associated with hypoalbuminemia 2
- Chronic infections (HIV, hepatitis, tuberculosis)
- Autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome) 2
- Inflammatory bowel disease 2
Critical Distinguishing Features
Monoclonal vs Polyclonal Pattern
Monoclonal gammopathy 1:
- Sharp, narrow peak (M-spike) on electrophoresis
- Associated with malignant or potentially malignant clonal process
- Requires bone marrow biopsy for definitive diagnosis 2
Polyclonal gammopathy 1:
- Broad-based elevation across gamma region
- Caused by reactive/inflammatory processes
- Generally benign but requires treatment of underlying condition
Additional Diagnostic Considerations
When Monoclonal Protein is Detected
Proceed with 2:
- Bone marrow biopsy - assess plasma cell percentage and clonality
- Skeletal survey or whole-body imaging - detect lytic lesions
- 24-hour urine collection - quantify urinary monoclonal protein (cannot use random samples) 2
- Serum calcium, creatinine, and hemoglobin - assess for myeloma-defining events 2
Common Pitfalls to Avoid
- Do not assume dehydration without confirming with SPEP - missing multiple myeloma has severe prognostic implications 2, 1
- Hypoalbuminemia with elevated total protein strongly suggests monoclonal gammopathy - the globulin fraction is disproportionately elevated 2, 1
- Normal total protein does not exclude plasma cell disorders - some patients have light chain-only disease 2
- Nephelometric quantitation may overestimate monoclonal protein when values are high - use densitometry for accurate measurement 2
Clinical Context Matters
The interpretation must consider 2:
- Patient age (monoclonal gammopathies increase with age, ~0.3% in adults 40-60 years) 3
- Presence of symptoms (bone pain, fatigue, recurrent infections suggest myeloma) 2
- Renal function (myeloma commonly causes renal insufficiency) 2
- Inflammatory markers (elevated CRP, ferritin suggest inflammatory causes) 2