White Blood Cell Count (WBC; Leukocyte Count)

Neutropenia causes and treatment

Neutropenia

Neutropenia is when a person has a low level of neutrophils. Neutrophils are a type of white blood cell. All white blood cells help the body fight infection. Neutrophils fight infection by destroying harmful bacteria and fungi (yeast) that invade the body. Neutrophils are made in the bone marrow. Bone marrow is the spongy tissue found in larger bones such as the pelvis, vertebrae, and ribs.

Neutropenia is present when the absolute neutrophil count is less than 1800/mcL (1.8 × 109/L), although blacks, Asians, and other specific ethnic groups may have normal neutrophil counts as low as 1200/mcL (1.2 × 109/L). The neutropenic patient is increasingly vulnerable to infection by gram-positive and gram-negative bacteria and by fungi. The risk of infection is related to the severity of neutrope­nia.

The risk of serious infection rises sharply with neutro­phil counts below 500/mcL (0.5 × 109/L), and a high risk of infection within days occurs with neutrophil counts below 100/mcL (0.1 × 109/L) (“profound neutropenia”). The clas­sification of neutropenic syndromes is unsatisfactory as the pathophysiology and natural history of different syn­dromes overlap.

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Patients with “chronic benign neutropenia” are free of infection despite very low stable neutrophil counts; they seem to physiologically respond adequately to infections and inflammatory stimuli with an appropriate neutrophil release from the bone marrow. In contrast, the neutrophil count of patients with cyclic neutropenia peri­odically oscillate (usually in 21-day cycles) between normal and low, with infections occurring during the nadirs. Con­genital neutropenia is lifelong neutropenia punctuated with infection.

Signs and symptoms of neutropenia

Neutropenia itself may not cause any symptoms. People usually find out they have neutropenia from a blood test or when they get an infection. Some people will feel more tired when they have neutropenia. Your doctor will schedule regular blood tests to look for neutropenia and other blood-related side effects of chemotherapy.

For people with neutropenia, even a minor infection can quickly become serious. Talk with your health care team right away if you have any of these signs of infection:

  • A fever, which is a temperature of 100.5°F (38°C) or higher
  • Chills or sweating
  • Sore throat, sores in the mouth, or a toothache
  • Abdominal pain
  • Pain near the anus
  • Pain or burning when urinating, or urinating often
  • Diarrhea or sores around the anus
  • A cough or shortness of breath
  • Any redness, swelling, or pain (especially around a cut, wound, or catheter)
  • Unusual vaginal discharge or itching

Diagnosis

Neutropenia results in stomatitis and in infections due to gram-positive or gram-negative aerobic bacteria or to fungi such as Candida or Aspergillus. The most com­mon infectious syndromes are septicemia, cellulitis, pneumonia, and neutropenic fever of unknown origin. Fever in neutropenic patients should always be initially assumed to be of infectious origin until proven other­wise

Treatment

Treatment of neutropenia depends on its cause. Potential causative medications should be discontinued. Myeloid growth factors (filgrastim or sargramostim or biosimilar myeloid growth factors) help facilitate neutrophil recov­ery after offending medications are stopped. Chronic myeloid growth factor administration (daily or every other day) is effective at dampening the neutropenia seen in cyclic or congenital neutropenia. When Felty syndrome leads to repeated bacterial infections, splenectomy has been the treatment of choice, but sustained use of myeloid growth factors is effective and provides a non­surgical alternative.

Patients with autoimmune neutrope­nia often respond briefly to immunosuppression with corticosteroids and are best managed with intermittent doses of myeloid growth factors. The neutropenia associ­ated with large granular lymphoproliferative disorder may respond to therapy with oral methotrexate, cyclophospha­mide, or cyclosporine.

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Fevers during neutropenia should be considered as infectious until proven otherwise. Febrile neutropenia is a life-threatening circumstance. Enteric gram-negative bac­teria are of primary concern and often empirically treated with fluoroquinolones or third- or fourth-generation cephalosporins. For protracted neutropenia, fungal infections are problematic and empiric coverage with azoles (fluconazole for yeast and voriconazole, itra­conazole, posaconazole, or isavuconazole for molds) or echinocandins is recommended.

The neutropenia fol­lowing myelosuppressive chemotherapy is predictable and is partially ameliorated by the use of myeloid growth factors. For patients with acute leukemia undergoing intense chemotherapy or patients with solid cancer under­going high-dose chemotherapy, the prophylactic use of antimicrobial agents and myeloid growth factors is recommended.

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