Low Ceruloplasmin and Leukopenia: Association Through Copper Deficiency
Low ceruloplasmin can be associated with low white blood cells when both are manifestations of copper deficiency, which can cause pancytopenia (including leukopenia). 1
Direct Association Through Copper Deficiency
The primary mechanism linking low ceruloplasmin to leukopenia is copper deficiency, which causes both conditions simultaneously:
- Copper deficiency causes pancytopenia (reduction in all blood cell lines, including white blood cells) and is specifically recognized as a cause of low ceruloplasmin levels. 1
- This occurs most commonly in patients receiving parenteral nutrition without adequate trace element supplementation. 1
- The appearance of pancytopenia alongside low ceruloplasmin should prompt immediate evaluation for copper deficiency. 1
Other Conditions With Low Ceruloplasmin
Low ceruloplasmin occurs in several conditions, but not all cause leukopenia:
Wilson's Disease
- Ceruloplasmin is typically decreased (usually <0.1 g/L), but leukopenia is not a characteristic feature. 1, 2
- Extremely low levels (<50 mg/L or <5 mg/dL) strongly suggest Wilson's disease. 1
- However, 10-36% of Wilson's disease patients may have normal ceruloplasmin levels, particularly children and those with hepatic inflammation. 1, 2
Menkes Disease
- This X-linked disorder of copper transport (ATP7A mutations) presents with both low ceruloplasmin and pancytopenia. 1
- This represents another copper metabolism disorder where both findings coexist. 1
Other Causes (Without Leukopenia)
- Protein loss states (renal or enteric): Low ceruloplasmin without hematologic abnormalities. 1
- Severe end-stage liver disease: Low ceruloplasmin from any etiology, but cytopenias would be from portal hypertension/hypersplenism rather than the low ceruloplasmin itself. 1
- Aceruloplasminemia: Complete absence of ceruloplasmin due to gene mutations, but these patients exhibit hemosiderosis (iron accumulation), not copper accumulation, and leukopenia is not characteristic. 1
Clinical Approach
When encountering low ceruloplasmin with leukopenia:
First, assess for copper deficiency, particularly in patients with:
Measure serum copper levels alongside ceruloplasmin to calculate free copper and assess copper status. 3
Consider Menkes disease in male infants with developmental delays and characteristic kinky hair. 1
Wilson's disease is less likely if leukopenia is the primary hematologic finding, as it typically does not cause isolated leukopenia (though hemolytic anemia can occur in acute presentations). 1
Critical Pitfall
Do not assume low ceruloplasmin automatically means Wilson's disease when leukopenia is present—this combination more strongly suggests copper deficiency requiring copper supplementation rather than copper chelation therapy. 1, 4 Treating presumed Wilson's disease with chelators in a copper-deficient patient would be catastrophic.