What are the causes of leukopenia?

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Last updated: February 11, 2025View editorial policy

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From the Guidelines

Leukopenia is primarily caused by bone marrow toxicity, certain malignancies, and immunosuppressive therapy.

Causes of Leukopenia

  • Bone marrow toxicity: Azathioprine (AZA) and 6-mercaptopurine, used to treat inflammatory bowel disease, can cause leukopenia due to bone marrow toxicity, with an incidence of 3.2% 1.
  • Malignancies: Certain malignancies, such as hematologic malignancies (chronic and acute leukemias, non-Hodgkin’s lymphoma) and myelodysplastic syndromes, can cause leukopenia due to infiltration of the marrow with malignant cells or a dysfunctional marrow 1.
  • Immunosuppressive therapy: Patients with advanced or refractory malignancy, particularly those receiving multiple chemotherapeutic regimens, are at increased risk of developing severe infections and leukopenia 1.
  • Other causes: Leukopenia can also occur due to other factors, such as anatomic factors in solid tumors, malnutrition, and previous surgery, chemotherapy, and radiation therapy 1. In patients with chronic myeloid leukemia (CML), leukopenia can occur due to the disease itself or as a result of tyrosine kinase inhibitor (TKI) therapy 1.

From the Research

Causes of Leukopenia

The causes of leukopenia can be varied and complex. Some of the possible causes include:

  • Infection, which can lead to increased utilization and destruction of white blood cells 2
  • Drugs, which can suppress the production of white blood cells in the bone marrow 2
  • Malignancy, which can infiltrate the bone marrow and disrupt the production of white blood cells 2
  • Megaloblastosis, a condition characterized by the presence of large, immature red blood cells in the bone marrow 2
  • Hypersplenism, a condition in which the spleen is overactive and destroys too many white blood cells 2
  • Immunoneutropenia, a condition in which the immune system attacks and destroys white blood cells 2
  • Familial Mediterranean fever (FMF), a genetic disorder that can cause episodic leukopenia due to autophagy and apoptosis processes 3
  • Congenital myelopathy, a rare condition that affects the production of white blood cells in the bone marrow 4
  • Immune-mediated neutropenias, which can occur in infancy and early childhood 4
  • Impaired proliferation and maturation of myeloid progenitor cells in the bone marrow, which can lead to intrinsic chronic neutropenia 5

Classification of Neutropenia

Neutropenia can be classified as:

  • Transient or chronic 5
  • Extrinsic or intrinsic 5 Extrinsic causes of neutropenia can be varied, while intrinsic causes can include impaired proliferation and maturation of myeloid progenitor cells in the bone marrow 5

Clinical Considerations

It is essential to assess patients with neutropenia systematically, considering the severity of presentation, duration of leukopenia, and clinical status of the patient 5. Patients with febrile neutropenia should undergo treatment with antibiotics, and other treatments should be aimed at managing the underlying cause of neutropenia 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The etiology and management of leukopenia.

Canadian family physician Medecin de famille canadien, 1984

Research

[Leucopenia in children].

Duodecim; laaketieteellinen aikakauskirja, 2011

Research

Hematologic Conditions: Leukopenia.

FP essentials, 2019

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.

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