Diagnostic Approach to Rule Out Amyloidosis

Introduction to Diagnostic Tests

The American Heart Association recommends serum and urine immunofixation electrophoresis to detect monoclonal proteins, along with serum free light chain (FLC) assay with kappa/lambda ratio to rule out AL (light chain) amyloidosis 1, 2, 3

Serum protein electrophoresis (SPEP) with immunofixation is used to detect monoclonal proteins, as recommended by the European Hematology Association 4, 3
Serum free light chain (FLC) assay with kappa/lambda ratio is used to detect abnormal immunoglobulin light chains, with a normal ratio of 0.26-1.65 (Binding Site method) or 0.31-1.56 (Siemens method) in patients with normal renal function, according to the International Myeloma Society 1, 2, 5
Quantitative immunoglobulins (IgG, IgA, IgM) are used to detect abnormal immunoglobulin levels, as recommended by the American Society of Hematology 4

The diagnostic algorithm for ATTR (transthyretin) cardiac amyloidosis requires negative monoclonal protein studies to avoid false positives, as stated by the American College of Cardiology 6
If serum/urine immunofixation and FLC ratio are normal, AL amyloidosis is effectively ruled out, according to the European Society of Cardiology 1, 2, 6

Immunohistochemistry uses antibodies against specific amyloid proteins to determine the type, including anti-kappa light chain antibodies, anti-lambda light chain antibodies, anti-transthyretin (TTR) antibodies, and anti-amyloid A antibodies, as recommended by the International Society of Amyloidosis 3, 1, 6, 7

The American Heart Association warns that never skipping monoclonal protein screening before interpreting a PYP scan can lead to false positives, and that immunohistochemistry alone is insufficient for amyloid typing due to antibody limitations 6, 7
Cardiac biomarkers (NT-proBNP ≥332 ng/L) are used for staging, not ruling out disease, as stated by the American College of Cardiology 1, 2, 5