Neutropenia is an abnormally low level of neutrophils in the blood. Neutrophils are white blood cells (WBCs) produced in the bone marrow and comprise approximately 60% of the blood. These cells are critically important to an immune response and migrate from the blood to tissues during an infection. They ingest and destroy particles and germs. Germs are microorganisms such as bacteria, protozoa, viruses, and fungus that cause disease. Neutropenia is an especially serious disorder for cancer patients who may have reduced immune functions because it makes the body vulnerable to bacterial and fungal infections. White blood cells are especially sensitive to chemotherapy. The number of cells killed during radiation therapy depends upon the dose and frequency of radiation, and how much of the body is irradiated.
Neutrophils can be segmented (segs, polys, or PMNs) or banded (bands) which are newly developed, immature neutrophils. If there is an increase in new neutrophils (bands) this may indicate that an infection is present and the body is attempting a defense. Neutropenia is sometimes called agranulocytosis or granulocytopenia because neutrophils display characteristic multi-lobed structures and granules in stained blood smears.
The normal level of neutrophils in human blood varies slightly by age and race. Infants have lower counts
than older children and adults. African-Americans have lower counts than Caucasians or Asians. The average adult level is 1, 500 cells/mm
3 of blood. Neutrophil counts (in cells/mm
3) are interpreted as follows:
Greater than 1, 000. Normal protection against infection.
500-1, 000. Some increased risk of infection.
200-500. Great risk of severe infection.
Lower than 200. Risk of overwhelming infection; requires hospital treatment with antibiotics.
Neutropenia has no specific symptoms except the severity of the patient's current infection. In severe neutropenia, the patient is likely to develop periodontal disease, oral and rectal ulcers, fever, and bacterial pneumonia. Fever recurring every 19-30 days suggests cyclical neutropenia.
Diagnosis is made on the basis of a white blood cell count and differential. The cause of neutropenia can be difficult to establish and depends on a combination of the patient's history, genetic evaluation, bone marrow biopsy, and repeated measurements of the WBC. However, in cancer patients it is usually an expected side effect of chemotherapy or radiation. The overall risk of infection is dependent upon the type of cancer an individual has as well as the treatment received. Patients at greater risk include those with hematologic malignancies, leukemia/lymphoma (cancers) and those who receive bone marrow transplants.
It is important to detect infections early. Some signs that indicate infection include:
coughing and difficulty breathing, congestion
an oral temperature greater than 105° with typical fever symptoms of chills and sweating
problems in the mouth such as white patches, sore and swollen gums
changes in urination or in stools
drainage and pain from any cuts or tubes used in the cancer treatments such as catheters and feeding tubes
an overall feeling of illness
Causes
Neutropenia may result from three processes:
Decreased WBC production
Lowered production of white blood cells is the most common cause of neutropenia. It can result from:
Medications that affect the bone marrow, including cancer drugs (chemotherapy), chloramphenicol (Chloromycetin), anticonvulsant medications, and antipsychotic drugs (Thorazine, Prolixin, and other phenothiazines). In hematopoietic stem cell transplantation (HSCT), high levels of total body irradiation (TBI) or chemotherapy are used to kill cancer cells, or these treatments may be combined. Two types of HSCT treatments are bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT). During the treatment process, the patient's normal bone marrow stem cells are killed along with the cancer cells. The stem cells are not able to mature into immune cells such as neutrophils, causing neutropenia. To reduce neutropenia, the normal stem cells from the patient may be removed prior to treatment and given back at a later time. Cells can also be supplied from another donor.
Hereditary and congenital disorders that affect the bone marrow, including familial neutropenia, cyclic neutropenia, and infantile agranulocytosis.
Sequestration and margination are processes in which neutrophils are removed from the general blood circulation and redistributed within the body. These processes can occur because of:
Bacterial infections. The neutrophils remain in the infected tissues without returning to the bloodstream.
Special Concerns
Often the infections that develop in a cancer patient are opportunistic infections. That is, the organisms responsible for the infection normally would not cause disease in a healthy person, but do so in a cancer patient because the immune system is weak. Several steps can be taken on a daily basis to reduce the risk of developing an infection.
Steps to Prevent Infection
Care should be taken to keep the body clean. Hands should be washed after using the bathroom and before eating.
Avoid stagnant or still water in the environment that might contain bacteria such as flower vases and birdbaths, or containers that may hold items such as dentures.
Use antiseptic mouthwashes to cleanse the mouth. Use those that do not contain alcohol.
Use deodorant. Antiperspirants will not allow the body to sweat, trapping bacteria within the body that may increase the risk of infection.
Women with neutropenia should consider using sanitary napkins instead of tampons during their menstruation to help prevent possible infection such as toxic shock syndrome.
Avoid others who are ill and large crowded areas where one might encounter illness.
Avoid activities that may increase the chance of physical injury. Take care to protect the body by wearing gloves, shoes, and other items. Tend to all injuries as soon as possible.
Neutropenic patients should consult their doctors before receiving any vaccinations.
Treatments
Treatment of neutropenia depends on the underlying cause.
Medications
Patients with fever and other signs of infection are treated with antibiotics. Some antibiotics used in the treatment of cancer patients include imipenem, meropenem, aminoglycoside, antipesudomonal penicillin, rifampin, and vancomycin. Combination therapy can be used that uses several types of antibiotics to stop the infection, but some of the drugs may be toxic or costly.
Patients receiving chemotherapy for cancer may be given drugs even in health to help restore the WBC to normal. A blood growth factor called sargramostim (Leukine, Prokine) stimulates WBC production. Another commonly used medication to reduce neutropenia in cancer patients is the cytokine G-CSF (granulocyte colony-stimulating factor, or filgrastim by Amgen-Roche). This substance is normally produced in the body at low levels. G-CSF helps the body produce more neutrophils to fight infection. This is especially useful in that many bacteria can not be killed by antibiotics due to antibiotic resistance.
Throughout the course of treatment it is important that the patient be monitored closely. This requires hospitalization for some patients, while others may be adequately treated at home.
Alternative and complementary therapies
A healthy lifestyle should be adopted that includes good nutrition, plenty of sleep, and appropriate levels of exercise. Avoid uncooked foods that may contain harmful bacteria. A nutritionist should be consulted to determine an appropriate, healthy diet.
Psychological stress can also weaken the immune system, making a person more susceptible to illness. It is important to find emotional support through family, friends, support groups, or through spiritual means.
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Janeway, Charles A., et al. Immunobiology:The Immune Sys tem in Health and Disease. London and New York: Cur rent Biology Publications, Elsevier Science London/Gar-land Publishing, 1999.
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Rahiala, J., Perkkio, M., and Pekka Riikonen. "Prospective and Randomized Comparison of Early Versus Delayed Pro phylactic Administration of Granulocyte Colony-Stimu lating Factor (Filgrastim) in Children With Cancer." Med ical and Pediatric Oncology 32 (1999): 326-30.
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—A rare genetic blood disorder in which the patient's neutrophil level drops below 500/mm
3 for six to eight days every three weeks.
Cytokine
—A type of protein produced by immune cells that affects the actions of other cells. Differential —A blood cell count in which the percentages of cell types are calculated as well as the total number of cells.
Granulocyte
—Any of several types of white blood cells that have granules in their cell substance. Neutrophils are the most common type of granulocyte.
Neutrophil
—A granular white blood cell that ingests bacteria, dead tissue cells, and foreign matter.
Opportunistic infection
— A type of infection caused by an organism that would not normally cause disease in a healthy person, but can do so when the immune system of the host is weakened.
Sargramostim
—A medication made from yeast that stimulates WBC production. It is sold under the trade names Leukine and Prokine.
Sequestration and margination
—The removal of neutrophils from circulating blood by cell changes that trap them in the lungs and spleen.
Filgrastim
—G-CSF cytokine normally produced in the body at low levels. G-CSF helps the body produce more neutrophils to fight infection.
QUESTIONS TO ASK THE DOCTOR
What symptoms lead to this diagnosis?
What can be expected with this condition and how long it last?
What is the plan for treatment? Will it be covered by my insurance? Can it be done at home?
What support and monitoring for home health care might be available? Would supervision be required? Would this be appropriate and what are the risks of complications? What are the costs?
What are the side effects of treatment? Are there any drugs, foods, etc. that should not be taken during treatment? Should daily activities be modified?
What complementary and alternative treatment methods have been shown to be helpful in addition to conventional medical treatments? Have any of these treatments been helpful to reduce symptoms and side effects from medication?
Are complementary treatments easy to access and what is the cost of such treatments? Are these covered by my insurance as well?
Where can a person get more information about this condition?
What avenues for emotional and spiritual support might be available to help cope with this diagnosis?
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