Neutropenia is defined as a low number of neutrophil granulocytes, a type of white blood cell, in the body. White blood cells serve as the body's primary defense mechanism against infection and disease. In a healthy body, neutrophils make up 50-60% of circulating white blood cells. Neutropenic patients have an absolute neutrophil count (ANC) that is lower than 1,500 cells per microliter of blood.
Therefore, patients with neutropenia are more susceptible to disease and infection. Severe cases of neutropenia may even become life threatening.
Mild neutropenia usually causes no symptoms. Severe neutropenia increases the risk of infection, especially in the lungs, kidneys, blood, and/or skin.
Neutropenia can be acute (lasting less than three months) or chronic (lasting longer than three months). The condition occurs when the bone marrow does not produce enough neutrophils or an increased number of neutrophils are destroyed in the body. For instance, neutropenia is a common side effect of chemotherapy.
About three out of every one million individuals are diagnosed with agranulocytosis, (the complete loss of neutrophils) every year, and about one out of every one million people is diagnosed with drug-induced neutropenia annually.
Individuals who experience infections during severe, prolonged episodes of neutropenia have an increased risk of fatality. Morbidity also correlates with the length of time elapsed before the first dose of antibiotics is administered for a neutropenic fever (which accompanies an infection). Serious medical complications, like infection, occur in about 21% of patients with cancer and neutropenic fever.
Morbidity usually involves infections during severe, prolonged episodes of neutropenia.
Infections associated with neutropenia are treated with antibiotics. Other symptoms of the disease may be treated with blood transfusions, recombinant G-CSF (granulocyte-colony stimulating factor), recombinant G-CSF (granulocytes colony-stimulating factor), corticosteroids, splenectomy (surgical removal of the spleen) or bone marrow transplant.
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Mild neutropenia: When an individual's ANC is greater than 1,000, but lower than 1,500, the condition is considered mild. Individuals with mild neutropenia have a slight risk of developing infections.
Moderate neutropenia: When an individual's ANC is greater than 500, but less than 1,000, the condition is considered moderate. Individuals have a moderate risk of developing infections.
Severe neutropenia (Kostmann's syndrome): When an individual's ANC is less than 500, the condition is considered severe. Individuals with severe neutropenia have a serious risk of developing infections, especially in the lungs, kidneys, blood and skin because these organs are exposed to the most bacteria. If this condition is accompanied by a fever, it is known as febrile neutropenia. Severe cases of neutropenia may result in agranulocytosis, which is the complete loss of neutrophils.
Autoimmune neutropenia (AIN):
Autoimmune neutropenia is most common among infants and young children. This form occurs when the body identifies the neutrophils as enemies and produces antibodies to destroy them. This type usually becomes less severe within about two years.
AIN is further classified as either primary or secondary. In primary AIN, neutropenia is the only abnormality. In secondary AIN, other pathologies occur, including systemic autoimmune disease, infections and malignancy. Secondary AIN is extremely rare in infants.
Congenital neutropenia: Congenital neutropenia (neutropenia at birth) is a rare form of the disease, which is usually discovered soon after birth. Individuals with this disease may experience premature loss of teeth and subsequent gum infections.
The most severe form of chronic congenital neutropenia, known as Kostmann's syndrome, is genetically heterogeneous. In most cases, an autosomal dominant mutation in the ELA2 gene causes the disease.
The gene responsible for many cases of the autosomal recessively inherited congenital neutropenia is HAX1. In this case, both parents have to be carriers of the recessive trait in order for the child to have congenital neutropenia. If both parents are carriers, there is a 25% chance that the child will have the disorder.
Some evidence suggests that mutations in neutrophils' elastase or in other genes linked to the syndromic forms of neutropenia disrupt its intracellular trafficking. The mutations may also initiate the unfolded protein response.
Other evidence suggests that there is an increase in apoptosis (cell death) of neutrophil precursors. However, these findings are controversial because some of the scientific data was falsified and retracted from publication.
Cyclic neutropenia: Cyclic neutropenia usually occurs every three weeks and lasts for about three to six days at a time. This form is frequently present among several members of the same family. In almost all cases, cyclic neutropenia is the result of autosomal dominantly inherited mutations in ELA2 gene, which encodes neutrophils' elastase.
Drug-induced: Many different types of drugs can cause neutropenia and agranulocytosis. Researchers estimate that about 75% of all cases of agranulocytosis in the United States are related to medication. Anti-neoplastic drugs suppress the bone marrow's production of neutrophils, which may lead to the disorder. Other drugs like clozapine, procainamide and anti-thyroid medications (like methimazole and sulfasalazine) can lead to the destruction of white blood cells. About 6-10% of drug-induced agranulocytosis cases are fatal.
Idiopathic neutropenia: Neutropenia is considered idiopathic when the disorder cannot be attributed to any other disease or condition. This form is rare, and it often causes life-threatening infections in both children and adults.