What blood investigations are recommended for diagnosing amyloidosis and sarcoidosis?

Blood Investigations for Amyloidosis and Sarcoidosis

For diagnosing amyloidosis and sarcoidosis, specific blood tests are essential to identify disease markers and exclude alternative diagnoses, with serum free light chain assay combined with serum and urine immunofixation being the gold standard for amyloidosis, while calcium testing and complete blood count are crucial for sarcoidosis.

Amyloidosis Blood Investigations

Essential Tests

• Serum free light chain (FLC) assay 1, 2, 3

  • Measures kappa and lambda free light chains and their ratio
  • Critical for detecting monoclonal light chains in AL amyloidosis
  • Abnormal kappa/lambda ratio indicates clonal light chain production

• Serum protein electrophoresis (SPEP) with immunofixation 4, 2

  • Identifies monoclonal proteins (M-proteins)
  • Must be combined with FLC assay for optimal sensitivity

• Urine protein electrophoresis with immunofixation (24-hour collection) 4, 2

  • Essential even when serum tests are negative
  • Detects Bence Jones proteins (free light chains in urine)

• Complete blood count 4

  • Evaluates for anemia, which occurs in ~22% of patients
  • Screens for other cytopenias

• Renal and liver function tests 4

  • BUN, creatinine, total protein
  • Liver enzymes to assess organ involvement

Additional Tests

• Quantitative immunoglobulins (IgG, IgA, IgM) 4

  • Helps characterize the underlying plasma cell disorder

• Beta-2 microglobulin and albumin 4

  • Important prognostic markers

• Cardiac biomarkers

  • Troponin and NT-proBNP/BNP for cardiac involvement 4
  • Critical for risk stratification

Sarcoidosis Blood Investigations

Essential Tests

• Serum calcium 4, 5

  • Strongly recommended for all sarcoidosis patients regardless of symptoms
  • Hypercalcemia occurs in ~6% of patients due to abnormal vitamin D metabolism

• Complete blood count with differential 4

  • Evaluates for anemia, leukopenia, and lymphopenia
  • Lymphopenia occurs in 27-55% of patients

• Vitamin D levels 4, 5

  • Both 25-OH and 1,25-(OH)₂ vitamin D should be measured
  • Abnormal pattern: normal/low 25-OH with elevated 1,25-(OH)₂ vitamin D

• Renal function tests 4

  • BUN, creatinine
  • Untreated hypercalcemia can lead to renal failure in 42% of patients

Additional Tests

• Angiotensin-converting enzyme (ACE) level 4

  • Elevated in many sarcoidosis patients
  • Not specific but supportive when elevated >50% above upper limit of normal

• Liver function tests 4

  • Alkaline phosphatase >3x upper limit may indicate hepatic involvement

• C-reactive protein (CRP) 4

  • Non-specific marker of inflammation

Diagnostic Pitfalls and Caveats

Amyloidosis

• No single test is sufficient for diagnosis 2

  • The combination of serum FLC assay with serum and urine immunofixation has 100% sensitivity
  • Using only FLC assay misses ~24% of cases
  • Using only immunofixation may miss cases with very small clones

• Tissue biopsy remains necessary 6

  • Blood tests identify the potential amyloidogenic protein
  • Definitive diagnosis requires demonstration of amyloid deposits in tissue

Sarcoidosis

• Hematologic abnormalities may be transient 4

  • Repeat testing may be necessary
  • Abnormalities often related to inflammatory mechanisms

• Calcium metabolism requires careful monitoring 4, 5

  • Vitamin D supplementation can precipitate hypercalcemia
  • Monitor calcium levels if vitamin D supplementation is initiated

Organ-Specific Considerations

Cardiac Involvement

• For suspected cardiac amyloidosis or sarcoidosis:
  • BNP or NT-proBNP is recommended for diagnosis and risk stratification 4
  • ECG should be performed at initial encounter 4

Renal Involvement

• 24-hour urine collection for total protein 4
  • Essential for monitoring renal involvement in amyloidosis
  • May detect nephrolithiasis with calcium stones in sarcoidosis

Algorithmic Approach

1. Initial screening panel for both conditions:

   • Complete blood count with differential
   • Comprehensive metabolic panel including calcium
   • Renal and liver function tests
   • ECG

2. For suspected amyloidosis, add:

   • Serum free light chain assay
   • Serum and urine immunofixation
   • Quantitative immunoglobulins
   • Cardiac biomarkers (NT-proBNP, troponin)

3. For suspected sarcoidosis, add:

   • 25-OH and 1,25-(OH)₂ vitamin D levels
   • ACE level
   • CRP

4. Follow-up testing based on initial results and clinical presentation

   • Tissue biopsy for definitive diagnosis
   • Organ-specific imaging as indicated