From the Guidelines
Elevated leukocytosis is primarily caused by infections, inflammatory conditions, physiological stress, hematologic disorders, and certain medications, with the most critical consideration being the management of hyperleukocytosis to prevent complications such as leukostasis and tumor lysis syndrome 1.
Causes of Leukocytosis
Leukocytosis, an elevated white blood cell count above 11,000 cells per microliter, has numerous potential causes, including:
- Infections, with bacterial infections typically causing more significant elevations than viral ones
- Inflammatory conditions like rheumatoid arthritis, vasculitis, and inflammatory bowel disease
- Certain medications, particularly corticosteroids, lithium, and some antibiotics, which may induce leukocytosis as a side effect
- Physiological stress, including surgery, trauma, burns, and even intense exercise or emotional distress, which can temporarily elevate white blood cell counts through cortisol release
- Hematologic disorders such as leukemia and myeloproliferative disorders, which cause pathological increases in white blood cells
- Tissue damage from conditions like myocardial infarction, pulmonary embolism, or pancreatitis, which triggers inflammatory responses leading to leukocytosis
- Splenectomy patients often have chronic mild leukocytosis due to the spleen's role in removing aging white blood cells
- Other causes include allergic reactions, certain cancers, and endocrine disorders like thyroid storm or diabetic ketoacidosis
Management of Hyperleukocytosis
The management of hyperleukocytosis, generally defined as a WBC count more than 100 × 10⁹/L, is crucial to prevent complications such as leukostasis and tumor lysis syndrome, with hydroxyurea being the recommended therapy to lower WBC counts, given at dosages up to 50 to 60 mg/kg per day, until WBCs are less than 10-20 × 10⁹/L 1. In children with hyperleukocytosis, initial management includes intravenous hyperhydration and hydroxyurea, with tyrosine kinase inhibitors (TKIs) started once the Ph chromosome or BCR::ABL1 fusion gene is detected 1. Prevention of tumor lysis syndrome is also essential, with hydration, control of uric acid production using allopurinol or rasburicase, and control of urine pH being critical components of management 1.
From the Research
Causes of Elevated Leukocytosis
- Infections or inflammatory processes are the most common causes of leukocytosis, leading to an increase in the number of white blood cells, predominantly polymorphonuclear leukocytes and less mature cell forms (the "left shift") 2
- Physical stress (e.g., from seizures, anesthesia or overexertion) and emotional stress can also elevate white blood cell counts 2
- Medications commonly associated with leukocytosis include corticosteroids, lithium and beta agonists 2
- Increased eosinophil or basophil counts, resulting from a variety of infections, allergic reactions and other causes, can lead to leukocytosis in some patients 2
- Primary bone marrow disorders, such as acute leukemias, chronic leukemias and myeloproliferative disorders, can cause extremely elevated white blood cell counts 2
- Systemic inflammation, disease progression, and poor prognosis can also be associated with elevated leukocyte count 3
- Fever and leukocytosis can be triggered by various factors, including infections, trauma, and inflammatory responses, but may not always be associated with urinary tract infections (UTIs) 4
- Burn wound colonization, infection, and sepsis can also lead to elevated leukocytosis, particularly in patients with compromised immune systems or those who are susceptible to infection 5
Risk Factors
- Male gender, older age, lower extremity burn, scald burn, full-thickness burn, delay in treatment, and pre-existing diabetes can increase the risk of infection and subsequent leukocytosis 5
- Female sex, older age, low Injury Severity Score, and no antibiotics within 24 h before the urine culture was obtained can increase the risk of UTIs 4
Clinical Implications
- Elevated leukocyte count can be a harbinger of systemic inflammation, disease progression, and poor prognosis, especially in older adults 3
- White blood cell counts above 100,000 per mm3 (100 x 10(9) per L) represent a medical emergency because of the risk of brain infarction and hemorrhage 2
- Prevention and early treatment of infections, as well as careful monitoring of white blood cell counts, are crucial in managing patients with elevated leukocytosis 2, 5