What could be an indication of a low white blood cell (WBC) count with a normal differential?

From the Guidelines

A low white blood cell (WBC) count with a normal differential can be an indication of bone marrow suppression, potentially caused by medications such as clozapine, an atypical antipsychotic, as noted in the study by 1. This condition may also result from viral infections, autoimmune disorders, nutritional deficiencies, or bone marrow disorders. The normal differential suggests that while the overall number of white blood cells is reduced, the relative proportions of neutrophils, lymphocytes, monocytes, eosinophils, and basophils remain within normal ranges. Some key points to consider include:

• Medications like clozapine can cause agranulocytosis, a potentially fatal condition, as seen in approximately 1% of patients, according to 1.
• Weekly blood cell counts are recommended during the first 6 months of treatment with clozapine, then every 2 weeks thereafter, to monitor for signs of bone marrow suppression.
• If the WBC drops below 2,000/mm3 or the absolute neutrophil count (ANC) drops below 1,000/mm3, the medication must be stopped immediately and the patient monitored for infection, as per the guidelines recommended by 1. Patients with low WBC counts should be monitored for infection risk, especially if counts fall below 1,000 cells/μL. Treatment focuses on addressing the underlying cause rather than the low count itself, though in severe cases, colony-stimulating factors might be prescribed to stimulate bone marrow production of white blood cells. It is essential to identify and manage the underlying cause of the low WBC count to prevent further complications and improve patient outcomes.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Indications of Low White Blood Cell Count with Normal Differential

• A low white blood cell (WBC) count with a normal differential can be an indication of various conditions, including:
  • Bone marrow suppression due to immunosuppressive treatment, such as azathioprine and mycophenolate mofetil 2
  • Viral infections, such as cytomegalovirus, which can aggravate bone marrow suppression 2
  • Medications, such as antiviral agents (gancyclovir), inhibitors of angiotensin-converting enzyme, and angiotensin II receptor antagonists, which can interfere with purine biosynthesis 2
  • Neutropenia, which is a common finding in the outpatient setting and can be caused by a significant reduction in neutrophils 3
  • Systemic lupus erythematosus (SLE) with cytopenias, which can be caused by an increase in SLE activity, immune-mediated hemolysis, or the effect of medications 4
  • Myelosuppression due to cancer treatment, which can result in infection and other serious clinical consequences 5
  • Chemotherapy-induced leukopenia, which can be a predictor of efficacy and survival in small-cell lung cancer patients 6

Possible Causes

• The possible causes of a low WBC count with a normal differential include:
  • Immunosuppressive treatment
  • Viral infections
  • Medications
  • Neutropenia
  • SLE with cytopenias
  • Myelosuppression due to cancer treatment
  • Chemotherapy-induced leukopenia

Clinical Implications

• A low WBC count with a normal differential can have significant clinical implications, including:
  • Increased risk of infection
  • Need for frequent patient assessment and aggressive management of infection
  • Potential for hematologic malignancies in patients with SLE and cytopenias 4
  • Association with survival in small-cell lung cancer patients 6