Laboratory Tests for Amyloid Workup
Essential Laboratory Tests
- The American College of Cardiology recommends obtaining serum free light chains (sFLC), serum immunofixation electrophoresis (SIFE), and urine immunofixation electrophoresis (UIFE) simultaneously for a comprehensive amyloid workup, as serum/urine protein electrophoresis (SPEP/UPEP) alone can miss up to 50% of cases due to low monoclonal protein levels in AL amyloidosis 1, 2, 3
- Serum free light chain (sFLC) assay measures kappa and lambda free light chains independently and calculates the kappa:lambda ratio, providing superior sensitivity compared to standard electrophoresis 1, 2, 3
- Serum immunofixation electrophoresis (SIFE) is more sensitive than SPEP for identifying and typing monoclonal immunoglobulins 2, 3, 4
- Urine immunofixation electrophoresis (UIFE) is essential because some patients have negative serum studies but positive urine findings 2, 3, 4
Additional Required Tests
- Bone marrow biopsy demonstrates clonal proliferation of lambda or kappa-producing plasma cells (or B cells), required to confirm AL amyloidosis diagnosis 1, 2, 3
- Bone marrow examination excludes multiple myeloma or B-cell lymphoproliferative disorders (rarely B-cell lymphoma) 1, 2
Tissue Diagnosis and Typing
- Mass spectrometry (LC-MS/MS) is the gold standard with 88% sensitivity and 96% specificity for identifying the amyloidogenic protein 1, 2, 3, 6, 5
- When LC-MS/MS is unavailable, transfer Congo red-positive samples to an experienced reference laboratory for definitive typing 1, 3
Special Considerations for Cardiac Amyloidosis
- Endomyocardial biopsy is required to definitively distinguish AL from ATTR cardiac amyloidosis when any monoclonal protein is present (even MGUS) 1, 2, 6
- Cardiac biopsy is preferred in suspected concomitant systemic AL and ATTR cardiac amyloidosis (MGUS with abnormal nuclear scintigraphy) 1, 2