Can Fungal Infection Cause Thrombocytosis?
Yes, fungal infections can cause thrombocytosis as part of a reactive inflammatory response, though this is less commonly emphasized than the association with leukocytosis. The elevation in platelet count occurs as a secondary phenomenon in response to systemic inflammation triggered by invasive fungal disease.
Mechanism and Clinical Context
Fungal infections trigger thrombocytosis through inflammatory cytokine release that stimulates thrombopoiesis. 1 This reactive thrombocytosis is part of the acute phase response to infection, similar to other inflammatory conditions. The platelet elevation typically accompanies other inflammatory markers including:
- Leukocytosis and neutrophilia 1, 2
- Fever despite broad-spectrum antibiotics 3, 1
- Elevated inflammatory markers 2
- Anemia (often concurrent) 2
Evidence Supporting the Association
Infection is a common cause of secondary thrombocytosis, accounting for nearly half of all secondary cases in one large retrospective analysis of 801 patients. 2 Clinical and laboratory characteristics that suggest an infectious (including fungal) etiology of thrombocytosis include:
- Fever and tachycardia 2
- Hypoalbuminemia 2
- Weight loss 2
- Presence of risk factors: indwelling prostheses, immunocompromised state, diabetes 2
Specific Fungal Infections Associated with Thrombocytosis
Invasive candidiasis and aspergillosis are the most clinically relevant fungal infections that can trigger thrombocytosis in immunocompromised patients. 1, 4 Key scenarios include:
- Hepatosplenic candidiasis: Presents after neutrophil recovery with fever, hepatosplenomegaly, and can be accompanied by leukocytosis and thrombocytosis 1
- Disseminated aspergillosis: Can present with thrombocytosis, particularly in patients with underlying hematologic conditions 5
- Mucormycosis (zygomycosis): Associated with thrombosis and vascular complications, though the thrombocytosis is secondary to the inflammatory response 6
Important Clinical Distinctions
The thrombocytosis from fungal infection is reactive and secondary, not primary. 2 Distinguishing features include:
- Timing: Rapid normalization of platelet count with infection treatment (unlike primary thrombocythemia) 2
- Magnitude: Usually moderate elevation (500-800 × 10⁹/L), whereas primary thrombocythemia more commonly causes extreme thrombocytosis (>800 × 10⁹/L) 2
- Duration: Shorter duration than primary causes 2
- Associated findings: Presence of other inflammatory markers and clinical signs of infection 2
Diagnostic Approach When Thrombocytosis is Present
When encountering thrombocytosis in an at-risk patient, consider invasive fungal infection if fever persists despite broad-spectrum antibiotics. 3, 1 The diagnostic workup should include:
- Blood cultures before initiating antifungal therapy 1
- β-D-glucan (Fungitell) testing for suspected invasive fungal infection 7
- Galactomannan testing if aspergillosis is suspected 7
- High-resolution chest CT for pulmonary infiltrates 7
- Site-specific cultures based on clinical presentation 7
Management Implications
Persistent thrombocytosis with fever despite antibacterial therapy should prompt empiric antifungal therapy in high-risk patients. 1 First-line options include:
- Echinocandins (caspofungin, micafungin, anidulafungin) as preferred empiric therapy 1
- Fluconazole in stable patients without prior azole exposure 1
- Lipid formulation amphotericin B in specific clinical scenarios 1
Source control is essential: Remove central venous catheters in candidemia, drain abscesses, and address underlying immunosuppression when possible. 7
Critical Pitfall to Avoid
Do not dismiss thrombocytosis as merely reactive without investigating for underlying infection, particularly in immunocompromised patients with persistent fever. 2 The presence of thrombocytosis with infection carries prognostic implications, as patients with infection-related thrombocytosis have higher mortality risk despite more rapid platelet count normalization compared to non-infectious causes. 2
Note on antifungal therapy causing thrombocytosis: Miconazole therapy itself has been reported to cause reversible thrombocytosis, though this is a rare drug-specific effect rather than a consequence of the infection. 8 This should not be confused with infection-related thrombocytosis.