Neutropenia: Causes, Symptoms & Treatment

Neutropenia refers to a decrease in neutrophil granulocytes in the blood. Neutrophil granulocytes play an important role in the body’s defense against infection, so neutropenia can cause severe general illness.

What is neutropenia?

Neutrophil granulocytes, also known as neutrophils for short, are the most common white blood cells (leukocytes). These specialized immune cells are part of the innate immune defense system. They serve to recognize and eliminate pathogenic microorganisms. The neutrophils can ingest and digest the microorganisms. In this process, they function as phagocytes. Furthermore, their granulavesicles contain various substances that can destroy bacteria and other pathogens. Furthermore, neutrophil granulocytes can form the so-called NETs (Neutrophil Extracellular Traps). These are chromatin structures that can bind microorganisms and thus render them harmless. These functions are limited in neutropenia due to the lack of neutrophil granulocytes. Normally, one microliter of blood contains 1800 to 8000 neutrophils. At 500 to 1000 neutrophils per microliter of blood, moderate neutropenia is present. Severe neutropenia begins at a neutrophil count below 500 per microliter of blood.

Causes

The cause of neutropenia may be at different levels. First, decreased formation of granulocytes may be responsible for neutropenia. The most important cause of such impaired formation is damage to the bone marrow. In this case, the bone marrow can be damaged by chemicals, toxic plants or by drugs such as diuretics, griseofulvin, chemotherapeutic agents, antibiotics, chloramphenicol or sulfonamides. Infections can also cause bone marrow damage. Bone marrow damage often occurs after infections with parvoviruses, in panleukopenias, or in feline leukemia virus. Immune-related or neoplastic bone marrow damage can also cause neutropenia. Neoplasms associated with bone marrow damage include leukemias or myelofibrosis. Increased granulocyte consumption can also lead to neutropenia. Neutrophil granulocytes are consumed particularly during acute inflammation. If the demand exceeds the production capacity of the bone marrow, there is a decrease in neutrophils in the blood. In this process, a so-called left shift occurs for a short time, in which only immature neutrophils and their precursor cells are released over a certain period of time. Neutropenia due to increased consumption occurs mainly in very severe diseases such as sepsis, metritis or peritonitis. So-called dysgranulopoiesis can also cause neutropenia. In dysgranulopoiesis, the formation of neutrophil granulocytes is disturbed. The cause may be in the developmental cycle of the immune cells or in reduced release. Dysgranulopoiesis may underlie acute myeloid leukemias, AIDS, feline leukemia, or myelodysplasias. Acute but transient neutropenia may be caused by a shift of neutrophil granulocytes into the neutrophil pool. Triggers for such a shift are endotoxins or anaphylaxis in the context of a severe allergic reaction. Congenital neutropenias occur rarely. Examples of such congenital neutropenias are Kostmann syndrome and glycogenosis type 1b.

Symptoms, complaints, and signs

Neutrophil leukocyte deficiency does not initially cause symptoms. However, affected individuals are significantly more susceptible to infections because the deficiency limits the functioning of the immune system. Severe neutropenia can thus lead to life-threatening infections. In addition, patients feel tired, weary and weak. They suffer from fever, occasionally in combination with chills. Painful ulcerations of the oral mucosa or gums are characteristic of neutropenia. These are often caused by a fungal infection called candidiasis.

Diagnosis and course of the disease

Increased susceptibility to infection quickly raises suspicion of a leukocyte deficiency. If the physician suspects neutropenia, he or she will have a blood sample tested in the laboratory. In the differential blood count, the individual blood cells are counted. In neutropenia, the blood count shows a clear deficiency of neutrophil granulocytes.In severe cases, there are only 500 neutrophils per microliter of blood. Once the diagnosis of neutropenia has been made, the cause must be identified as quickly as possible. The history and clinical examination provide clues to the disease of origin. Other symptoms such as weakness, shortness of breath, bone pain or a feeling of pressure in the abdomen may indicate leukemia. It may even be possible to palpate an enlarged spleen. A bone marrow biopsy can be taken from the pelvic bone to rule out an educational disorder in the bone marrow as the cause.

Complications

Neutropenia carries a high risk of serious bacterial infections because the immune response is markedly decreased due to the reduced number of neutrophil granulocytes. However, infection with viruses is not more likely. It is a clinical picture which, in addition to congenital causes, is often in turn a complication of an underlying disease. Furthermore, it can also be a consequence of taking certain medications or undergoing certain treatments. These risk factors can even lead to the complete loss of neutrophil granulocytes with devastating effects. The complete absence of the corresponding granulocytes, also known as agranulocytosis, is characterized by a very severe clinical picture with chills, fever and greatly increased heart rate. This is caused by a regular bacterial invasion of the body with bacteria. With the absence of neutrophil granulocytes, the body’s initial defense against these invaders is also absent. In addition to the fever and chills, there is death of the mucous membranes in the pharynx (throat), tonsils (tonsils) and even in the anal as well as genital area. This is accompanied by local swelling of the lymph nodes. In the mouth area, painful aphthae develop in the form of stomatitis aphtosa. Agranulocytosis can in turn lead to life-threatening sepsis. To save patients’ lives, strict infection control and discontinuation of precipitating drugs are required in addition to the use of broad-spectrum antibiotics.

When should you go to the doctor?

Low blood pressure, fever, and chills are signs of neutropenia. Anyone who notices these symptoms should consult their primary care physician. Medical advice is especially needed for complaints that seem to occur for no reason and are associated with physical malaise. In these cases, neutropenia may be the underlying cause, which, if left untreated, can lead to further physical problems. If signs of infection are noticed, a hospital visit is recommended. People who suffer from the above-mentioned complaints in connection with chemotherapy or radiotherapy should inform the responsible physician. People with an immune disorder also belong to the risk groups and it is best to consult the family doctor quickly. The physician can diagnose neutropenia and initiate treatment. People with a relevant medical history (low blood pressure, cardiovascular disease, etc.) should also seek medical advice. In addition to the family doctor’s office, the cardiologist or an internist can be consulted. Depending on the cause, physiotherapists and alternative doctors may also be involved in the treatment. Children are best presented to the pediatrician when the aforementioned symptoms occur.

Treatment and therapy

Therapy depends on the underlying disease. For symptomatic treatment, patients receive granulocyte colony-stimulating factor (G-CSF). G-CSF is a peptide hormone that stimulates granulocyte formation. The drug is produced from either E. coli or CHO cells. The four major cancer societies recommend preventive treatment with G-CSF when the risk of neutropenia is 20 percent. Reverse isolation may be required. Reverse isolation involves isolating people with weak immune systems. Staying in special isolation wards in hospitals is intended to protect patients from infectious diseases. In isolation wards, there are locks outside patients’ rooms. Staff and visitors are allowed to enter the rooms only with protection and after certain disinfection measures. Causative therapy must be given regardless of symptomatic therapy. If the neutropenia is due to a severe infectious disease, the blood values will return to normal after the infection has subsided.Diseases of the bone marrow, on the other hand, require special treatment.

Outlook and prognosis

The clarification of the cause in neutropenia is crucial for the further course of the disease and thus for the prognosis. Frequently, a determination of the health condition occurs only after a long period of time. Patients usually suffer from an increased susceptibility to infections, so that the actual diagnosis of neutropenia usually takes place very late. The earlier the cause can be determined, the better the further course. A special therapy is necessary to treat the patient in the best possible way. Drug therapy can provide considerable relief from the symptoms. In addition, in some cases a bone marrow transplant is necessary to achieve an improvement of the general health condition. A complete recovery is not achieved in many patients despite all efforts. The treatment is associated with numerous complications, so that a cure is not always given. The patient requires long-term treatment as well as regular medical check-ups to ensure that the organism is supported in the best possible way. Since the disease is associated with a number of impairments, it represents an immense burden for the patient as well as his relatives. Everyday life has to be adapted to the physical conditions. This often leads to the affected person reporting a reduced sense of well-being in the long term, and psychological secondary disorders are possible. Often, stays in isolated wards are necessary to achieve improvements.

Prevention

Most neutropenias cannot be prevented. If there is an increased risk with chemotherapy, G-CSF can be given as a preventive measure.

Follow-up

In most cases, the measures and options for follow-up care in neutropenia are significantly limited. For this reason, the affected person should seek immediate medical attention at the first signs and symptoms of the disease to prevent the further occurrence of other complications and symptoms. It is not possible for the disease to heal on its own, so medical treatment is unavoidable. Most patients are dependent on regular checks and examinations by a doctor during treatment in order to detect and remove further tumors at an early stage. Neutropenia patients should protect themselves particularly well against various infections. Often, care and support from one’s own family is also very important, which can alleviate the development of depression and other psychological upsets. The patient should rest and take it easy, refraining from exertion and from physical activities in order not to put unnecessary strain on the body. In some cases, neutropenia can also reduce the life expectancy of the affected person. Further measures of aftercare are usually not available to the patient in this case.