What can cause elevated procalcitonin levels without leukocytosis (elevated white blood cell count)?

From the Guidelines

Elevated procalcitonin levels without leukocytosis can occur in several clinical scenarios, including severe viral infections, fungal infections, non-infectious conditions, and certain medications or malignancies, as supported by recent studies 1. These conditions can trigger procalcitonin release without significantly increasing white blood cell counts. Some of the major causes include:

• Severe viral infections, particularly COVID-19 and influenza, which can trigger procalcitonin release without significantly increasing white blood cell counts 1
• Fungal infections, which may similarly elevate procalcitonin while maintaining normal leukocyte levels
• Non-infectious conditions like major trauma, burns, surgery, cardiogenic shock, and acute kidney injury, which can increase procalcitonin through inflammatory pathways without affecting white blood cell counts
• Certain medications, particularly immunosuppressants and chemotherapy agents, which may suppress leukocyte production while inflammation continues to drive procalcitonin release
• Autoimmune disorders, which can trigger procalcitonin elevation through inflammatory cascades without leukocytosis
• Malignancies, particularly medullary thyroid carcinoma, which can directly produce procalcitonin independent of infection This discordance occurs because procalcitonin and leukocytes respond to different stimuli and signaling pathways - procalcitonin primarily responds to bacterial endotoxins and inflammatory cytokines, while leukocytosis depends on bone marrow response and cellular migration, which may be impaired in certain conditions 1. Additionally, a study on severe acute pancreatitis found that serum measurements of procalcitonin may be valuable in predicting the risk of developing infected pancreatic necrosis, further highlighting the complexity of procalcitonin elevation in various clinical scenarios 1.

From the Research

Causes of Elevated Procalcitonin without Leukocytosis

Elevated procalcitonin levels without leukocytosis can be caused by various factors, including:

• Bacterial infections, particularly those caused by Gram-negative bacteria 2
• Sepsis, severe sepsis, and septic shock 3, 4
• Intestinal infection 4
• Diabetic ketoacidosis with proven bacterial infection 5
• Bacterial meningitis 6

Conditions that May Lead to Elevated Procalcitonin without Leukocytosis

Some conditions that may lead to elevated procalcitonin levels without an increase in white blood cell count include:

• Immunocompromised states, such as those with hematological malignancies or autoimmune diseases 3
• Systemic inflammatory response syndrome (SIRS) without infection 3
• Severe disease, as indicated by high APACHE II scores 3, 2
• Certain types of bacterial infections, such as those caused by Gram-negative bacteria 2

Diagnostic Value of Procalcitonin

Procalcitonin has been shown to be a useful diagnostic marker for:

• Bacterial infections, particularly those caused by Gram-negative bacteria 2
• Sepsis, severe sepsis, and septic shock 3, 4
• Diabetic ketoacidosis with proven bacterial infection 5
• Bacterial meningitis 6
• Differentiating between bacterial and abacterial meningitis 6