What Does a Copper RBC Test Tell You?
A copper RBC (red blood cell) test is not a recommended or validated diagnostic tool for Wilson's disease or other copper metabolism disorders, and major clinical guidelines do not include it in their diagnostic algorithms. 1
Why RBC Copper Testing Is Not Used Clinically
The European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) guidelines comprehensively outline diagnostic tests for Wilson's disease, and RBC copper measurement is notably absent from these recommendations. 1 This omission is significant because these guidelines extensively detail all validated copper-related tests including:
- Serum ceruloplasmin (the primary screening test) 2, 1
- 24-hour urinary copper excretion (typically >100 μg/24 hours or 1.6 μmol/24 hours in Wilson's disease) 2
- Hepatic parenchymal copper concentration (>250 μg/g dry weight provides best biochemical evidence) 2
- Calculated non-ceruloplasmin-bound (free) copper (elevated above 200-250 μg/L in untreated Wilson's disease) 2, 3
- Slit-lamp examination for Kayser-Fleischer rings 1
Limited Research Context Only
While RBC copper has been studied in research settings, particularly in animal models of Wilson's disease, it has not been validated for clinical use. 4 In LEC rats (an animal model for Wilson's disease), copper in RBCs was found to increase 5-7 times higher than plasma levels at the onset of acute hepatitis, with the pattern similar to plasma copper changes. 4 However, this finding has not translated into a clinically useful human diagnostic test.
The key issue is that RBC copper measurement lacks the diagnostic accuracy, standardization, and clinical validation that established tests possess. 1
What You Should Order Instead
When evaluating for copper metabolism disorders, the validated diagnostic approach includes:
- First-line screening: Serum ceruloplasmin measurement, with extremely low levels (<50 mg/L or <5 mg/dL) strongly suggesting Wilson's disease 1
- Calculate free copper: Non-ceruloplasmin bound copper using the formula: Free copper (μg/L) = Total serum copper (μg/L) - (3.15 × ceruloplasmin in mg/L), with levels >250 μg/L supporting Wilson's disease 2, 3
- 24-hour urinary copper: Values >100 μg/24 hours (1.6 μmol/24 hours) indicate Wilson's disease, though >40 μg (>0.6 μmol) warrants further investigation 2, 1
- Hepatic copper quantification: If diagnosis remains unclear, particularly in younger patients, with levels >250 μg/g dry weight providing critical diagnostic information 2, 1
Common Pitfall to Avoid
Do not assume that total serum copper alone is diagnostic. Total serum copper is often decreased in Wilson's disease (proportional to decreased ceruloplasmin), not elevated. 2, 1 The exception is acute liver failure from Wilson's disease, where serum copper may be markedly elevated due to sudden release from tissue stores. 2, 3 This is why calculating free copper and measuring urinary copper excretion are essential components of the diagnostic workup. 1, 3