Leukocytosis and Leukopenia

General Principles


  • Leukocytosis is an elevation in the absolute WBC count (>10,000 cells/μL).
  • Leukopenia is a reduction in the WBC count (<3500 cells/μL).


  • Leukocytosis
    • An elevated WBC can be the normal BM response to an infectious or inflammatory process, corticosteroids, β-agonist or lithium therapy, or splenectomy and is usually associated with an absolute neutrophilia.
    • Occasionally, leukocytosis is due to a primary BM disorder with an increase in WBC production and/or delayed maturation. This may occur in the setting of hematologic malignancies such as leukemias and can affect any cell in the leukocyte lineage.
    • A “leukemoid reaction” is defined as an excessive WBC response usually reserved for neutrophilia (>50,000/μL) due to a reactive cause.
    • Lymphocytosis is less commonly encountered and is typically associated with atypical infections (i.e., viral), medication use, or leukemia/lymphoma.
  • Leukopenia
    • Leukopenia can be classified as either congenital or acquired.
    • Acquired leukopenia can occur in response to infection (i.e., HIV), inflammation, primary BM disorders (i.e., malignancy), autoimmune disorders, medications, environmental exposure (i.e., heavy metals or radiation), and vitamin deficiencies. Many cases are medication induced (i.e., chemotherapeutic or immunosuppressive drugs) and a careful history examining the timing of the onset of leukopenia/neutropenia and new medications is important.
    • Large granular lymphocytic leukemia can be a cause of neutropenia, especially in patients with rheumatoid arthritis.
    • Congenital neutropenias can include constitutional/ethnic neutropenia, severe congenital neutropenia, and cyclic neutropenia.


Diagnostic Testing

  • Review of the peripheral smear is very helpful in the evaluation of WBC disorders. Predominant neutrophilia may suggest a reactive process. The presence of blasts is concerning for acute leukemia and warrants emergent evaluation.
  • Flow cytometry of the blood may help determine if there is an underlying clonal process in lymphocytosis (i.e., CLL) or if an acute leukemia is suspected.
  • A BCR–ABL molecular study may be warranted in cases of unexplained neutrophilia to diagnose chronic myeloid leukemia (CML), especially if there is associated eosinophilia or basophilia.

Diagnostic Procedures

A BM biopsy with ancillary studies such as cytogenetics, special stains, and flow cytometry may be required to establish the diagnosis.


  • The primary goal of therapy is identification and treatment of the underlying cause.
  • See Chapter 22, Cancer, for the treatment of acute and chronic leukemia.
  • Growth factor support should be considered in patients with chronic neutropenia and ongoing infections until the neutropenia resolves (see Oncologic Emergencies in Chapter 22, Cancer).


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