Neutropenia

Key Features

Essentials of Diagnosis

• Neutrophils < 1800/mcL

• Severe neutropenia if neutrophils < 500/mcL

General Considerations

• Patients with neutropenia are vulnerable to gram-positive and gram-negative bacterial and fungal infections

• Risk of infection is related to the severity of neutropenia

• Patients with "chronic benign neutropenia" are free of infection despite very low stable neutrophil counts

• In patients with cyclic neutropenia, the neutrophil count oscillates (usually in 21-day cycles) between normal and low, with infections occurring during the nadirs

• Congenital neutropenia is lifelong neutropenia punctuated with infection

• Both cyclic neutropenia and congenital neutropenia represent problems in mutations in the neutrophil elastase gene ELANE (also called ELA-2)

Etiology

• A variety of bone marrow disorders and nonmarrow conditions may cause neutropenia (Table 13–12)

• All the causes of aplastic anemia and pancytopenia may cause neutropenia

  • Causes of aplastic anemia

    • Autoimmune: idiopathic, systemic lupus erythematosus

    • Congenital: defects in telomere length maintenance or DNA repair (rare)

    • Chemotherapy, radiotherapy

    • Toxins: benzene, toluene, insecticides

    • Medications: chloramphenicol, gold salts, sulfonamides, phenytoin, carbamazepine, quinacrine, tolbutamide

    • Post-viral hepatitis (A, B, C, E, G, non-A through -G)

    • Non-hepatitis viruses (Epstein-Barr virus, parvovirus, cytomegalovirus, echovirus 3, others)

    • Pregnancy

    • Paroxysmal nocturnal hemoglobinuria

  • Causes of pancytopenia

    • Aplastic anemia

    • Myelodysplasia

    • Acute leukemia

    • Chronic idiopathic myelofibrosis

    • Infiltrative disease: lymphoma, myeloma, carcinoma, hairy cell leukemia, etc

    • Hypersplenism (with or without portal hypertension)

    • Systemic lupus erythematosus

    • Infection: tuberculosis, HIV, leishmaniasis, brucellosis, cytomegalovirus, parvovirus B19

    • Nutritional deficiency (megaloblastic anemia)

    • Medications

    • Cytotoxic chemotherapy

    • Ionizing radiation

• New onset of an isolated neutropenia is most often due to an idiosyncratic reaction to a drug

• Agranulocytosis (complete absence of neutrophils in the peripheral blood) is almost always due to a drug reaction

• Neutropenia in the presence of a normal bone marrow may be due to

  • Immunologic peripheral destruction (autoimmune neutropenia)

  • Sepsis

  • Hypersplenism

• Isolated neutropenia is an uncommon presentation of hairy cell leukemia or a myelodysplastic syndrome

• Myelosuppressive cytotoxic chemotherapy causes neutropenia in a predictable manner

Clinical Findings

• Neutropenia results in

  • Stomatitis

  • Infections due to gram-positive or gram-negative aerobic bacteria or to fungi such as Candida or Aspergillus

• Most common infectious syndromes

  • Septicemia

  • Cellulitis

  • Pneumonia

  • Neutropenic fever of unknown origin

• Fever should always be assumed to be of infectious origin until proven otherwise

Diagnosis

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