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Learning Objectives

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  1. Learn the differential diagnosis of leukopenia.

    Distinguish between neoplastic and nonneoplastic proliferations of white blood cells.

  2. Learn the diagnostic criteria for the different types of lymphomas, leukemias, myelodysplastic syndromes, myeloproliferative disorders, and plasma cell dyscrasias.

  3. Understand the genetic, biochemical, and/or cellular defects associated with the more commonly encountered disorders of WBC function.

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A bnormalities in white blood cells (WBCs) are nearly always quantitative (eg, too many or too few WBCs). These disorders may be neoplastic, as found in leukemia, or nonneoplastic. A qualitative or functional disorder of WBCs may accompany the quantitative disorder. Qualitative defects in WBC function with a normal WBC count occur, but they are uncommon. The approach to diagnosis of WBC disorders is shown in Figure 13–1.

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Figure 13–1

An approach to the patient with a white blood cell disorder.

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Leukopenia

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Description and Diagnosis

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A low WBC count can occur because of a decreased number of lymphocytes, granulocytes, or both. A number of the immunodeficiency diseases are associated with a lymphocytopenia (see Chapter 3). Granulocytopenia primarily reflects a reduction in the number of neutrophils (neutropenia) in the peripheral blood. When the number of neutrophils decreases below about 1000 neutrophils/μL, the neutropenic patient becomes susceptible to infections. These illnesses range from mild to severe, depending on the type of organism and the effectiveness of the antibiotics used to treat it. A classification of granulocytopenic disorders follows.

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A low WBC count can occur because of a decreased number of lymphocytes, granulocytes, or both.

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Defects in the production of granulocytes may be caused by:

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  • Diseases associated with marrow failure, such as aplastic anemia.

  • Diseases in which the marrow is infiltrated by leukemic cells or by metastatic cancer cells originating from another site; the decreased neutrophil production in this setting is typically associated with defects in the production of other blood cells as well.

  • Suppression of granulocyte production by exposure to certain drugs; the list of drugs that can produce neutropenia is extensive; noteworthy examples are chemotherapeutic agents used in cancer treatment and certain nonsteroidal anti-inflammatory drugs (NSAIDs).

  • Vitamin B12 or folate deficiency; these disorders produce a megaloblastic anemia and defective DNA synthesis in granulocyte precursors.

  • Suppression of granulocyte production by neoplastic cells, for example, large granular lymphocytic leukemia.

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Accelerated removal of granulocytes may be caused by:

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  • Immunologically mediated injury to neutrophils following exposure to drugs, with the injury occurring from an immune response on the neutrophil surface.

  • Immunologically mediated injury to neutrophils as part of an autoimmune disorder; for example, Felty syndrome is a variant of rheumatoid arthritis with neutropenia, splenomegaly, leg ulcers, and the joint lesions found in rheumatoid arthritis; the neutropenia can dominate the clinical course in patients with Felty syndrome.

  • Immunologically ...

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