Does Lithium Cause Leukocytosis?
Yes, lithium commonly causes leukocytosis, which is a well-documented and expected side effect that occurs in the majority of patients receiving lithium therapy. 1
Mechanism and Clinical Significance
Lithium-induced leukocytosis is a benign, drug-related phenomenon that does not represent an infectious or pathological process. 2, 3
- The FDA drug label explicitly lists "leucocytosis" as an adverse reaction unrelated to dosage, along with other miscellaneous reactions. 1
- This effect is mediated through lithium's inhibition of glycogen synthetase kinase-3beta (GSK3β), which stimulates proliferation of bone marrow stem cells and enhances granulocyte production. 4
Expected White Blood Cell Changes
The typical increase in WBC count averages approximately 2,200 cells/mm³ above baseline values, with most patients developing counts in the range of 11,000-12,000 cells/mm³. 2
- Leukocytosis develops within the first few weeks of lithium therapy and persists throughout long-term treatment. 5, 6
- The elevation is not dose-dependent and does not correlate with serum lithium levels, though some studies suggest a correlation with lithium dose rather than serum concentration. 2, 6
- The leukocytosis is predominantly due to increased polymorphonuclear leukocytes (neutrophils), with associated granulocytosis and relative lymphopenia. 4
Clinical Management Implications
This leukocytosis should not be mistaken for infection or other pathological conditions, and routine monitoring should account for this expected elevation. 3
- When evaluating patients on lithium with elevated WBC counts, clinicians must distinguish between benign lithium-induced leukocytosis and pathological causes requiring intervention. 3
- Baseline complete blood cell counts should be obtained before initiating lithium therapy to establish the patient's pre-treatment WBC baseline. 7
- The leukocytosis is reversible upon discontinuation of lithium therapy. 2, 5
Therapeutic Applications
Lithium's leukocyte-stimulating properties have been exploited therapeutically to treat leukopenic conditions. 5, 6, 4
- Lithium has been used clinically to treat granulocytopenia resulting from radiation and chemotherapy. 4
- Lower-than-conventional lithium doses may be sufficient for managing certain leukopenic conditions while minimizing other side effects. 6
Important Caveats
Do not confuse lithium-induced leukocytosis with the leukocytosis that can occur in acute lithium toxicity, which may be accompanied by serious systemic symptoms. 1
- In the context of lithium toxicity (serum levels >1.5 mEq/L), leukocytosis may be part of a more complex clinical picture requiring immediate intervention. 1
- Extreme leukocytosis (WBC >100,000/mm³) would be highly unusual with lithium alone and should prompt evaluation for primary bone marrow disorders. 3