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Protein Electrophoresis

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Used to analyze the different protein fractions in the blood or urine, helping diagnose various diseases

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Protein Electrophoresis - Comprehensive Medical Test Guide

  • Why is it done?
    • Separates blood proteins into distinct fractions (albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, and gamma globulin) using an electrical field to identify abnormal protein patterns
    • Detects monoclonal and polyclonal immunoglobulins to diagnose multiple myeloma, Waldenström macroglobulinemia, and other plasma cell dyscrasias
    • Evaluates protein abnormalities in patients with unexplained symptoms, chronic infections, autoimmune diseases, or suspicious laboratory findings
    • Investigates abnormal total protein levels or albumin-to-globulin ratio to determine underlying pathology
    • Monitors disease progression and treatment response in patients with known hematologic malignancies or protein disorders
    • Performed when patients present with bone pain, recurrent infections, renal dysfunction, hypercalcemia, or anemia suggestive of malignancy
  • Normal Range
    • Albumin: 50-65% of total protein or 3.5-5.5 g/dL (reference range may vary by laboratory)
    • Alpha-1 Globulin: 2-3% of total protein or 0.1-0.3 g/dL
    • Alpha-2 Globulin: 5-10% of total protein or 0.3-0.7 g/dL
    • Beta Globulin: 8-15% of total protein or 0.6-1.2 g/dL
    • Gamma Globulin: 12-22% of total protein or 0.7-1.6 g/dL (primarily immunoglobulins)
    • Total Serum Protein: 6.0-8.3 g/dL
    • Albumin-to-Globulin Ratio: 1.0-2.5 (typically 1.5-2.5 in healthy adults)
    • Monoclonal Spike: Absent (negative) - no discrete protein band should be visible
    • Interpretation of Results:
    • Normal: All protein fractions within expected ranges; smooth, gradual protein pattern on electrophoresis; no discrete monoclonal spike
    • Abnormal Low Albumin: Below 3.5 g/dL indicates malnutrition, liver disease, nephrotic syndrome, or severe inflammation
    • Abnormal Elevated Gamma Globulin: Above 1.6 g/dL suggests infection, autoimmune disease, or hematologic malignancy
    • Monoclonal Spike (M-Spike): Discrete narrow band indicating presence of single immunoglobulin clone; concerning for malignancy if clinically significant
  • Interpretation
    • Monoclonal Spike Pattern: A sharp, discrete band in the gamma region is pathognomonic for plasma cell dyscrasia. Height and width of spike correlate with disease burden. Most commonly indicates multiple myeloma, light chain disease, or monoclonal gammopathy of undetermined significance (MGUS)
    • Polyclonal Hypergammaglobulinemia: Broad elevation in gamma region indicates response to multiple antigens from chronic infection (tuberculosis, hepatitis), autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), or chronic inflammation
    • Hypoalbuminemia: Decreased albumin with elevated globulins suggests nephrotic syndrome, liver cirrhosis, malnutrition, or chronic disease. Pattern called 'reverse albumin-to-globulin ratio' when A/G ratio falls below 1.0
    • Beta-Gamma Bridging: Elevated proteins in both beta and gamma regions with bridging pattern indicates chronic liver disease and immune activation
    • Biclonal Pattern: Two discrete monoclonal spikes indicate two separate clones; rare but seen in some lymphoproliferative disorders or concurrent malignancies
    • Elevated Alpha-1 Globulin: May indicate acute phase response, alpha-1 antitrypsin measurement needed if suspected deficiency (emphysema, chronic lung disease risk)
    • Elevated Alpha-2 Globulin: Associated with acute phase response, nephrotic syndrome (alpha-2 macroglobulin), or hemolysis (haptoglobin)
    • Elevated Beta Globulin: May reflect transferrin elevation (iron deficiency anemia) or complement proteins (immune activation)
    • Factors Affecting Results: Age, medications (corticosteroids, immunosuppressants), pregnancy, dehydration, malignancy progression, treatment response, specimen hemolysis, improper collection
  • Associated Organs
    • Primary Organ Systems:
    • Lymphoid System (bone marrow, lymph nodes, spleen) - site of plasma cell and immunoglobulin production
    • Liver - major site of albumin synthesis and acute phase protein production
    • Immune System - B cells and plasma cells produce immunoglobulins detected in electrophoresis
    • Kidneys - affected by light chain disease and amyloidosis from abnormal proteins; can cause proteinuria
    • Diseases/Conditions Associated with Abnormal Results:
    • Hematologic Malignancies: Multiple myeloma (IgG, IgA, or light chain disease), Waldenström macroglobulinemia (IgM), light chain myeloma, monoclonal gammopathy of undetermined significance (MGUS)
    • Liver Disease: Cirrhosis (decreased albumin, elevated globulins), hepatitis (polyclonal hypergammaglobulinemia), liver failure (markedly decreased albumin)
    • Renal Disease: Nephrotic syndrome (decreased albumin, elevated alpha-2 globulin), chronic kidney disease, light chain nephropathy, amyloidosis
    • Autoimmune/Inflammatory Disorders: Systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome (polyclonal hypergammaglobulinemia), vasculitis
    • Infections: Tuberculosis, chronic hepatitis (B/C), endocarditis, osteomyelitis, HIV (elevated gamma globulin)
    • Nutritional/Metabolic Disorders: Malnutrition, protein malabsorption, iron deficiency anemia (elevated beta globulin from transferrin)
    • Genetic Disorders: Alpha-1 antitrypsin deficiency (decreased alpha-1 globulin), familial amyloidosis
    • Potential Complications from Abnormal Results:
    • Multiple myeloma: Bone destruction, hypercalcemia, renal failure, spinal cord compression, severe anemia, infections from immunosuppression
    • Light chain disease: Acute kidney injury, chronic kidney disease, dialysis-dependent renal failure from light chain deposition disease
    • Amyloidosis: Cardiac dysfunction, neuropathy, hepatomegaly, multiorgan failure
    • Severe hypoalbuminemia: Edema, ascites, coagulopathy, malnutrition, impaired drug binding
    • Hyperviscosity syndrome: Stroke risk, bleeding, vision loss, neurologic symptoms from increased blood viscosity
  • Follow-up Tests
    • If Monoclonal Spike Detected:
    • Immunofixation electrophoresis - identifies specific immunoglobulin type (IgG, IgA, IgM, IgD, IgE, kappa, lambda)
    • Serum free light chain assay - quantifies kappa and lambda chains; detects light chain disease
    • 24-hour urine protein and urine immunoelectrophoresis - detects Bence Jones proteinuria
    • Bone marrow biopsy and aspirate - assesses plasma cell percentage and morphology; needed for myeloma diagnosis
    • Complete blood count - evaluates for anemia, thrombocytopenia, leukopenia
    • Chemistry panel - assesses calcium, creatinine (renal function), albumin
    • Imaging studies (skeletal survey or PET-CT) - detects bone lesions in myeloma
    • If Hypoalbuminemia Detected:
    • Liver function tests (AST, ALT, bilirubin, prothrombin time) - evaluates hepatic synthetic function
    • Urinalysis and urine protein quantification - detects nephrotic syndrome (>3.5 g/day proteinuria)
    • Serum albumin level - confirms degree of hypoalbuminemia
    • Prealbumin level - assesses nutritional status and acute phase response
    • If Polyclonal Hypergammaglobulinemia Detected:
    • ANA and rheumatoid factor - screens for autoimmune/rheumatologic disease
    • Infectious disease serology (HIV, hepatitis B/C, TB testing, syphilis) - evaluates for chronic infections
    • Inflammatory markers (CRP, ESR) - assesses degree of systemic inflammation
    • If Alpha-1 Globulin Abnormality:
    • Alpha-1 antitrypsin level and phenotyping - diagnoses alpha-1 antitrypsin deficiency
    • Pulmonary function tests - assesses lung disease severity from AAT deficiency
    • Monitoring Frequency for Known Conditions:
    • Multiple myeloma: Every 4-12 weeks during active treatment; monthly to quarterly during maintenance; every 3-6 months in remission to detect relapse
    • MGUS: Every 3-6 months initially; annually once stable (risk of progression 1% per year)
    • Liver cirrhosis: Every 3-6 months to assess disease progression and synthetic function
    • Nephrotic syndrome: As clinically indicated based on treatment response and disease course
  • Fasting Required?
    • Fasting Required: No - fasting is not required for protein electrophoresis
    • Patient Preparation:
    • No fasting required - patient may eat and drink normally prior to blood draw
    • Inform phlebotomist of any medications currently being taken
    • Continue all regular medications unless specifically instructed otherwise by physician
    • Arrive at collection site well-hydrated to ensure adequate blood volume for testing
    • Avoid strenuous exercise or stress immediately before blood draw as these may affect protein levels
    • Specimen Collection:
    • Blood draw is performed via routine venipuncture into serum separator tube (SST) or plain tube
    • Approximately 5-10 mL of blood is collected; volume depends on laboratory requirements
    • Specimen should be allowed to clot completely at room temperature for 15-30 minutes if using SST
    • Serum is separated by centrifugation; hemolyzed specimens should be rejected and recollected
    • Specimen is stable at room temperature for 24 hours or refrigerated for up to 7 days
    • Medications to Avoid:
    • No medications need to be discontinued specifically for protein electrophoresis
    • However, corticosteroids and immunosuppressive agents can alter immunoglobulin levels and should be documented
    • Inform provider of all current medications to interpret results appropriately in clinical context
    • Special Instructions:
    • If monitoring for disease (myeloma, MGUS), timing of collections should be consistent (same time of day preferred) for trend assessment
    • Recent transfusions can temporarily alter protein results; defer test 1-2 weeks if possible after transfusion
    • Pregnancy can elevate total protein and globulins; physician should be aware of pregnancy status
    • Severe dehydration or overhydration can affect serum protein concentrations; ensure patient is well-hydrated but not acutely ill

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