What is Neutropenia?

-NEUTROPENIA, Causes, Consequences, and Care, Provided by The Neutropenia Association Inc.1993

Neutropenia is a blood disorder that can affect anyone. Some people are born with it. It can happen after a viral infection. In some cases the cause can be a side effect of a drug, or exposure to certain poisons. People can get neutropenia when treated for cancer with chemotherapy drugs. Sometimes it happens for no known reason.

Blood is made up of billions of cells. There are many different types of blood cells, but most of the time you hear about two kinds - red cells and white cells. There are more red cells than any other type of blood cell. They are very important as they carry oxygen from your lungs to all parts of your body. White blood cells are just as important, but for a very different reason. One of their jobs is to protect you from infection. There are several kinds of white cells. Each has a special function. The most common ones are:

Neutrophils (pronounced NEW TROH FILS), which surround and destroy bacteria in your body; and

Lymphocytes (pronounced LIM FOH SITES), which are the key part of your body’s immune system, and defend against viruses.

A third kind of blood cell, the platelet, helps your blood to clot.

The term neutropenia describes the situation where the number of neutrophils in the blood is too low. Neutrophils are very important in defending the body against bacterial infections, and therefore, a patient with too few neutrophils is more susceptible to bacterial infections.

Everyone has been sick with an infection at one time or another. That’s because it’s easy for bacteria and viruses that cause infections to get inside the body. Healthy people don’t often get infections even though bacteria and viruses are all around us, even in the air we breathe.

The body protects itself against the constant risk of infection by making a lot of neutrophils. They are your main defense against infections.

People with neutropenia get infections easily and often. Most of the infections occur in the lungs, mouth and throat, sinuses and skin. Painful mouth ulcers, gum infections, ear infections and periodontal disease are common. Severe, life-threatening infections may occur. Often the child or adult must be hospitalized and receive intravenous antibiotics. Your doctor uses blood tests

to find out whether you have enough neutrophils.

The level of neutropenia may vary considerably. In general, the blood of healthy adults contains about 1500 to 7000 neutrophils per mm3 (1.5 - 7.0 x 109 /1). In children under 6 years of age the neutrophil count may be lower. The severity of neutropenia generally depends on the absolute neutrophil count (ANC) and is described as follows:

* Mild neutropenia, when the ANC falls below a lower limit of 1500 per mm3 (1.5 x 109 /1), but remains higher than 1000 per mm3 (1.0 x 109 /1).

* Moderate neutropenia, when the ANC falls between 500 per mm3 and 1000 per mm3 (0.5 x 109 /1 - 1.0 x 109 /1)

* Severe neutropenia, when the ANC falls below 500 per mm3 (0.5 x 109 /1)

The duration of the neutropenia may be short lived. In short-lived cases, the patient is described as suffering from acute neutropenia. However, if a patient has neutropenia for a longer period, i.e. greater than three months, the patient is described as suffering from chronic neutropenia.

Symptoms which patients experience depend on the level of neutropenia. The lower the neutrophil count, the greater the risk of infection. This risk increases if low neutrophil counts persist for more than three days. Types of infection include otis media; tonsillitis; sore throat; mouth ulcers; gum infection and skin abscesses. Any fever (body temperature above 38.5° C/101.3° F) must be taken very seriously and your nurse or physician should be informed.

Severe neutropenia can lead to serious problems, which require prompt care and attention as the patient could potentially develop a bacterial, fungal or mixed infection at any time. These infections can be life threatening when the patient is persistently severe neutropenic and it is therefore important that if the patient develops any signs or symptoms of an infection, then he or she should be seen by a doctor as soon as possible and treated with medications to fight the infection (such as antibiotics).

Incidence of Severe Chronic Neutropenia
The true incidence of severe chronic neutropenia is now known, but these are rare haematological disorders. Based on case findings in the Puget Sound area of western Washington in the US, it is estimated that there is approximately one case per 100,000 population (Dale, unpublished observations). Cyclic neutropenia is probably the rarest syndrome, with an estimated frequency of one per million. Congenital and idiopathic neutropenia are more common, with an estimated frequency of one per 200,000 population. Estimates in other regions suggest perhaps a somewhat lower incidence. Mild neutropenia is more common in certain racial and ethnic groups; it is not known if severe chronic neutropenia is more common in these populations.

Severe chronic neutropenia is most frequently encountered as a paediatric problem. Children born with severely reduced neutrophils have a great predilection for infections, due to the combination of the reduced neutrophils and immaturity of a variety of the components of the host’s defense system. Across the spectrum of these patients, clinical symptoms tend to diminish with increasing age, despite persistence of low neutrophil counts.

Congenital, cyclic and chronic idiopathic neutropenia are primarily attributed to impaired neutrophil production.

Congenital Neutropenia
There are several forms of congenital neutropenia varying in the severity of reduction of neutrophil counts and the associated clinical problems. In one severe form, congenital agranulocytosis or Kostmann’s syndrome, neutrophils are severely reduced from birth, often to less than 0.1 x 109 /L. There is often a mild increase in blood monocytes and blood and marrow eosinophils, but the reasons for this observation are not known. The increase may be due to higher levels of endogenous haematopoietic growth factors during chronic inflammation, or because production of blood cells is diverted away from the neutrophil lineae. Neutrophil counts are always quie low, but in some patients, in response to severe illness and infection, slightly higher counts may be observed. Many of these patients have chronic infections with secondary anemia and elevated platelet counts. When severe hypoproliferative anemia or significant thrombocytopenia are seen in neonates and very young children, other diagnoses such as congenital aplastic anemia should be considered. In other patients with congenital neutropenia, still with counts usually less than 0.5 x 109 /L. Data from large series of cases indicate that there are indistinct boundaries between patients who might be classified as having Kostmann’s syndrome or congenital agranulocytosis, and those regarded as having more benign forms of congenital neutropenia.

Marrow examinations show a range of abnormalities from "maturation arrest" at the promyelocyte stage to nearly complete maturation of the neutrophilic series.

Who distinctive groups of patients with severe congenital neutropenia have a relative abundance of marrow neutrophils with severe reductions in patients with glycogen storage type 1B, maturation of marrow neutrophils appears to be complete, but blood counts are very low and a similar pattern of infections and inflammation occur as in the older congenital neutropenias.

Also see Types of Severe Chronic Neutropenia

Cyclic Neutropenia
In cyclic neutropenia considerable evidence from human studies and from investigations of an analogous disease in collie dogs indicate that a regulatory defect at the haematopoietic stem cell level leads to oscillations in production of all typ

es of blood cells. In most patients with cyclic neutropenia, blood neutrophil counts oscillate between mild and severe neutropenia, with counts usually of 0.1 x 109 /L for three to six days with every cycle. It is during these severely neutropenic periods that these patients are particularly predisposed to fever and infection. Characteristically, after the neutropenic period, blood neutrophil counts recover rapidly. Although the other blood cells, including monocytes, eosinophils, lymphocytes, platelets and reticulocytes all ascillate, their oscillations are generally around a mean value which are normal, whereas the mean value for neutrophils is almost always in the moderate to severe neutropenia range.

Also see Types of Severe Chronic Neutropenia

Chronic Idiopathic Neutropenia
Chronic idiopathic neutropenia is a general term for cases of severe chronic neutropenia not clearly falling into the cyclic or congenital categories. These patients are described as having normal neutrophil counts earlier in life and an acquired pattern of recurrent problems with infections. In some of these cases immune mechanisms are suspected, but it is often difficult to separate them reliably from those with neutropenia on a truly idiopathic basis. The marrow defect in these patients is generally less than in congenital neutropenia but a deficiency of neutrophils in the most-miotic pool is usually observed.

Also see Types of Severe Chronic Neutropenia

Other types of Severe Chronic Neutropenia
Although sporadic cases of neutropenia with distinctive morphological abnormalities have been described, there is no unifying set of morphological findings characteristic for cyclic, congenital or chronic idiopathic neutropenia. These diagnoses are made by excluding other causes and by observing patients and their symptoms over time. The diagnosis of cyclic neutropenia usually requires observation of counts approximately three times per week for about six to eight weeks. Congenital neutropenia is distinguished from immunoneutropenia of the newborn by its persistence after the first few weeks to months of life and by specific antibody tests. Congenital cases are generally subcategorized on the basis of associated physical findings and abnormalities in other organ systems. Chronic idiopathic neutropenia is also diagnosed by excluding infectious, malignant, premalignant and autoimmune disorders.

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