What is the cause of leukocytosis (elevated white blood cell count)?

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Last updated: March 8, 2025 • View editorial policy

From the Guidelines

Leukocytosis is primarily caused by an underlying condition that stimulates the body to increase white blood cell production, such as infections, inflammation, or leukemia, as evidenced by the need for immediate medical treatment in cases of hyperleukocytosis 1. The condition of leukocytosis, or an elevated white blood cell count, is a sign of the body's response to various stimuli, including infections, inflammation, tissue damage, and certain diseases like leukemia.

Common Causes of Leukocytosis

  • Infections (bacterial, viral, fungal, or parasitic)
  • Inflammation
  • Tissue damage
  • Certain medications (corticosteroids, epinephrine)
  • Leukemia or other bone marrow disorders
  • Allergic reactions
  • Stress
  • Exercise In the context of hyperleukocytosis, which is defined as a WBC count more than 100 10^9/L, the condition is associated with increased induction mortality mainly due to hemorrhagic events, tumor lysis syndrome, and infections 1.

Management of Leukocytosis

The management of leukocytosis depends entirely on identifying and treating the underlying cause.

  • For infection-related leukocytosis, appropriate antibiotics or antimicrobials are prescribed based on the specific pathogen.
  • For inflammatory conditions, anti-inflammatory medications may be indicated.
  • If medication-induced, discontinuing the offending drug may resolve the condition.
  • For leukemias, chemotherapy or other cancer treatments are necessary, and in cases of hyperleukocytosis, hydroxyurea given at dosages up to 50 to 60 mg/kg per day can be used to lower the WBC count until it is less than 10-20 10^9/L 1. A complete blood count with differential is essential for proper evaluation, as the specific type of elevated WBCs provides important diagnostic clues.

Diagnostic Approach

  • A complete blood count (CBC) with differential count to identify the specific type of white blood cells that are elevated
  • Other tests may be ordered based on the suspected underlying cause, such as blood cultures for infections or imaging studies for tissue damage or inflammation. In real-life clinical practice, it is crucial to prioritize the identification and treatment of the underlying cause of leukocytosis to improve patient outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

Leukocytosis

Investigations Other rarely observed adverse reactions (<0. 1%) include ... leukocytosis

The cause of leukocytosis (elevated white blood cell count) is not explicitly stated in the drug label as being directly related to ceftriaxone therapy. It is only mentioned as one of the rarely observed adverse reactions. Therefore, based on the provided information, no conclusion can be drawn about the cause of leukocytosis. 2

From the Research

Causes of Leukocytosis

  • Leukocytosis, or an elevated white blood cell count, can be caused by various factors, including infections, inflammatory processes, physical stress, emotional stress, and certain medications 3, 4, 5.
  • Primary bone marrow disorders, such as acute leukemias, chronic leukemias, and myeloproliferative disorders, can also lead to leukocytosis 3, 4.
  • Medications commonly associated with leukocytosis include corticosteroids, lithium, and beta agonists 3, 6.
  • Increased eosinophil or basophil counts, resulting from infections, allergic reactions, or other causes, can also contribute to leukocytosis 3, 7.

Physiologic Responses

  • The normal reaction of bone marrow to infection or inflammation leads to an increase in the number of white blood cells, predominantly polymorphonuclear leukocytes and less mature cell forms (the "left shift") 3.
  • Stressors capable of causing an acute leukocytosis include surgery, exercise, trauma, and emotional stress 5.
  • Certain medications, asplenia, smoking, obesity, and chronic inflammatory conditions can also cause nonmalignant leukocytosis 5.

Clinical Evaluation

  • A thorough history, physical examination, and peripheral blood smear are essential in evaluating patients with leukocytosis 4, 5.
  • Constitutional symptoms, such as fever, weight loss, bruising, or fatigue, may suggest a hematologic malignancy 5.
  • Patients with chronic leukemias usually present with less severe symptoms than those with acute leukemias 4.
  • Urgent referral to a hematology subspecialist is indicated in cases of suspected acute leukemia 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Leukocytosis: basics of clinical assessment.

American family physician, 2000

Research

Evaluation of Patients with Leukocytosis.

American family physician, 2015

Research

Inpatients With 'Unexplained' Leukocytosis.

The American journal of medicine, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.