What causes leukopenia (low white blood cell count)?

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Last updated: June 19, 2025View editorial policy

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From the Guidelines

Leukopenia, or a low white blood cell count, is most commonly caused by bone marrow disorders, viral infections, and certain medications, as evidenced by recent studies 1. The causes of leukopenia can be multifaceted, including:

  • Bone marrow disorders like leukemia, myelodysplastic syndrome, and aplastic anemia
  • Viral infections such as influenza, HIV, and hepatitis
  • Certain medications, including chemotherapy drugs, antibiotics like chloramphenicol, and immunosuppressants
  • Autoimmune disorders, including lupus and rheumatoid arthritis
  • Congenital disorders like Kostmann syndrome
  • Radiation exposure
  • Severe infections that overwhelm the immune system
  • Nutritional deficiencies, particularly of vitamin B12 and folate
  • Splenomegaly, or an enlarged spleen, which can trap and destroy white blood cells According to the most recent guidelines 1, treatment of leukopenia depends on identifying and addressing the underlying cause. For medication-induced leukopenia, stopping or changing the medication may help. For nutritional deficiencies, supplementation with appropriate vitamins is recommended. Severe cases might require medications to stimulate white blood cell production, such as filgrastim (Neupogen) at doses of 5-10 mcg/kg/day subcutaneously until counts recover. In cases of bone marrow failure, more intensive treatments, including bone marrow transplantation, might be necessary. It is essential to note that leukopenia can significantly compromise the immune system's ability to protect the body, making prompt and effective treatment crucial to prevent infections and other complications, as highlighted in studies on cancer-related infections 1 and hairy cell leukemia 1.

From the FDA Drug Label

Chronic Use of sulfamethoxazole and trimethoprim at high doses and/or for extended periods of time may cause bone marrow depression manifested as thrombocytopenia, leukopenia and/or megaloblastic anemia. The cause of leukopenia (low white blood cell count) is bone marrow depression due to chronic use of sulfamethoxazole and trimethoprim at high doses and/or for extended periods of time 2.

  • Key factors that contribute to leukopenia include:
    • High doses of sulfamethoxazole and trimethoprim
    • Extended periods of use
    • Bone marrow depression as a result of this use.

From the Research

Causes of Leukopenia

Leukopenia, a condition characterized by a low white blood cell count, can result from various factors. The main causes include:

  • Reduced production of white blood cells
  • Increased utilization and destruction of white blood cells
  • Infection
  • Drugs, such as penicillin and cephalosporin homologues 3
  • Malignancy
  • Megaloblastosis, often caused by folic acid or vitamin B12 deficiency 4
  • Hypersplenism
  • Immunoneutropenia

Classification and Assessment

Leukopenia can be classified as transient or chronic, with chronic neutropenia further described as extrinsic or intrinsic 5. Assessment of patients with neutropenia should consider the severity of presentation, duration of leukopenia, and clinical status of the patient.

Diagnostic Approach

A diagnostic approach to leukopenia involves checking previous blood counts to understand the dynamic development of the condition 6. Additionally, a manual counted peripheral blood smear can provide essential information on potential causes, such as dysplasia.

Treatment and Management

Management of leukopenia requires identification of the underlying cause and effective antimicrobial therapy, especially in cases of serious systemic infection 7, 5. Patients with febrile neutropenia should undergo treatment with antibiotics, and other treatments should aim at managing the underlying cause of neutropenia. In some cases, such as agranulocytosis with fever, immediate admission and treatment with broad-spectrum antibiotics are necessary to reduce mortality 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Leukopenia due to penicillin and cephalosporin homologues.

Archives of internal medicine, 1979

Research

Megaloblastic anemia.

Postgraduate medicine, 1978

Research

Hematologic Conditions: Leukopenia.

FP essentials, 2019

Research

[Leukopenia - A Diagnostic Guideline for the Clinical Routine].

Deutsche medizinische Wochenschrift (1946), 2017

Research

The etiology and management of leukopenia.

Canadian family physician Medecin de famille canadien, 1984

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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