What is the cause of leukocytosis with toxic granulation?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: April 3, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Leukocytosis with toxic granulation is a strong indicator of an underlying bacterial infection, and prompt treatment with broad-spectrum antibiotics is essential to reduce morbidity and mortality. This condition is characterized by an elevated white blood cell count (leukocytosis) with neutrophils containing dark, coarse granules in their cytoplasm (toxic granulation). The presence of toxic granulation in neutrophils is a sign of the body's heightened immune response to bacterial pathogens, as noted in studies such as 1.

Key Considerations

  • The likelihood ratio of 3.7 for leukocytosis with a leukocyte count of 14,000 cells/mm3, as reported in 1, indicates a high probability of an underlying bacterial infection.
  • The management of leukocytosis with toxic granulation involves identifying and treating the underlying infection, with blood cultures obtained before starting empiric antibiotic therapy.
  • Initial antibiotic selection depends on the suspected source of infection, with broad-spectrum coverage often including a combination of ceftriaxone and vancomycin, or piperacillin-tazobactam for more severe cases, as would be considered in the context of guidelines like those discussed in 1.

Treatment Approach

  • Broad-spectrum antibiotic therapy should be initiated promptly, with the selection of antibiotics depending on the suspected source of infection and the severity of the condition.
  • Supportive care, including IV fluids, antipyretics, and close monitoring of vital signs, is essential to manage the patient's condition and prevent complications.
  • The antibiotic regimen should be narrowed based on culture results and clinical response, to ensure effective treatment and minimize the risk of antibiotic resistance.

From the Research

Leukocytosis with Toxic Granulation

  • Leukocytosis refers to an elevated white blood cell count, which can be caused by various factors including infections, inflammatory conditions, and certain medications 2.
  • Toxic granulation is a condition where the white blood cells exhibit abnormal granules, which can be a sign of infection or other underlying conditions 2.
  • The presence of toxic granulation in leukocytosis can indicate a severe infection or an inflammatory response 2.

Causes of Leukocytosis with Toxic Granulation

  • Infections, particularly bacterial infections, can cause leukocytosis with toxic granulation 2.
  • Certain medications, such as beta-lactam antibiotics, can also cause leukocytosis with toxic granulation 3.
  • Other non-malignant etiologies of leukocytosis include asplenia, smoking, obesity, and chronic inflammatory conditions 2.

Cefepime-Induced Leukocytosis

  • Cefepime is a broad-spectrum antibiotic that can cause leukocytosis with toxic granulation in some patients 3.
  • The mechanism of cefepime-induced leukocytosis is thought to be secondary to either an immune-mediated response or direct bone marrow toxicity 3.
  • Rechallenge with a different beta-lactam antibiotic has not been shown to consistently cause recurrent leukopenia, but cefepime has been reported to cause leukocytosis with toxic granulation in some cases 3.

Diagnosis and Management

  • A repeat complete blood count with peripheral smear may provide helpful information, such as types and maturity of white blood cells, uniformity of white blood cells, and toxic granulations 2.
  • The leukocyte differential may show eosinophilia in parasitic or allergic conditions, or it may reveal lymphocytosis in childhood viral illnesses 2.
  • Symptoms suggestive of a hematologic malignancy include fever, weight loss, bruising, or fatigue, and referral to a hematologist/oncologist is indicated if malignancy cannot be excluded 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Evaluation of Patients with Leukocytosis.

American family physician, 2015

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.