What blood tests are used to diagnose amyloidosis?

Blood Tests for Diagnosing Amyloidosis

For patients with suspected amyloidosis, screening for serum and urine monoclonal light chains with serum and urine immunofixation electrophoresis and serum free light chain assay is the essential first step in diagnosis. 1

Diagnostic Approach to Amyloidosis

Initial Blood Tests

• Serum and urine monoclonal protein screening:
  • Serum immunofixation electrophoresis (SIFE)
  • Urine immunofixation electrophoresis (UIFE)
  • Serum free light chain (sFLC) assay

This combination is critical as it helps differentiate between the two most common types of amyloidosis:

• AL amyloidosis (immunoglobulin light chain)
• ATTR amyloidosis (transthyretin)

Diagnostic Algorithm

1. Step 1: Blood and urine testing for monoclonal proteins

   • If positive: Suggests AL amyloidosis → Hematology referral
   • If negative: Proceed to bone scintigraphy for ATTR evaluation 1

2. Step 2: Based on results:

   • If monoclonal protein detected: Tissue biopsy required to confirm AL amyloidosis 1
   • If no monoclonal protein and positive bone scan (grade 2-3 uptake): Suggests ATTR amyloidosis 1

Important Considerations

Cardiac Biomarkers

• NT-proBNP (>332 ng/L has >99% sensitivity for cardiac involvement)
• Troponin T/I/high-sensitivity troponin
• These are supportive but not diagnostic 2

Diagnostic Pitfalls to Avoid

• Never interpret bone scintigraphy without first performing monoclonal protein screening 1

  • 10% of AL amyloidosis patients can have positive cardiac uptake on bone scans

  • A positive bone scan without excluding monoclonal proteins can lead to misdiagnosis

• Serum protein electrophoresis (SPEP) alone is insufficient 1

  • Lower sensitivity compared to immunofixation
  • AL amyloidosis often has low levels of monoclonal protein

Special Situations

• Renal dysfunction: May cause disproportionate urinary loss of lambda light chains 1
  • Collaborate with hematology to determine if findings are due to:
    • Kidney dysfunction
    • Monoclonal gammopathy of undetermined significance (MGUS)
    • True AL amyloidosis
    • Multiple myeloma

Follow-up Testing After Initial Blood Work

• For suspected ATTR: Genetic testing with TTR gene sequencing to differentiate hereditary variant from wild-type ATTR 1

• For suspected AL with positive monoclonal proteins:

  • Bone marrow biopsy showing clonal proliferation of lambda or kappa-producing plasma cells
  • Tissue biopsy (abdominal fat pad aspiration has 84% sensitivity for AL amyloidosis) 1

Conclusion

Blood testing for amyloidosis must begin with serum and urine immunofixation electrophoresis and serum free light chain assay. This is the critical first step that determines the subsequent diagnostic pathway and should never be skipped, even when proceeding with imaging studies.