What is Neutropenia

Neutropenia is a disorder of the blood, with low levels of a special type of cell called the neutrophil. There are many types of cells in the blood, but the two main kinds are red blood cells and white blood cells.
A neutrophil is a type of white blood cell, which helps destroy bacteria in the body. Therefore someone who has low levels of neutrophils is more likely to get bacterial infections. There are many causes for neutropenia – sometimes it can occur after an infection, ingestion of a particular drug or some people can be born with it. If the neutrophil levels fall extremely low, the condition is called agranulocytosis.

Statistics on Neutropenia

Internationally the incidence of agranulocytosis is 3.4 cases per million persons per year. The incidence of drug-induced neutropenia is 1 case per million persons per year.

Risk Factors for Neutropenia

Patients can be at increased risk of neutropenia due to congenital (patient is born with the condition) or acquired causes.
Congenital:

  • Chronic benign neutropenia: This group of people can be born with low levels of neutrophils and experience only mild infections.

 

  • Congenital immune defects: These patients have abnormal levels of immunoglobulins (part of a group of large proteins secreted by white cells, called plasma cells, that play an important part in our body’s immune response) and have a high infection risk.

 
 

  • Congenital or chronic neutropenias: This group includes Kostmann syndrome, which is a severe neutropenia apparent in babies by age 3 months, with the child experiencing recurrent bacterial infections.

 
 

  • Idiopathic chronic severe neutropenia: Some cases of neutropenia occur when there is no known or apparent cause.

 
 

  • Neutropenia associated with phenotypic (observable physical features of an organism, as determined by both genetic makeup and environmental factors) abnormalities: there are some conditions such as Shwachman syndrome and Barth syndrome, which are associated with specific physical abnormalities and a moderate to severe neutropenia.

 
 

  • Metabolic diseases: These include glycogen storage diseases. Variable neutrophil counts are observed.

 
 

  • Immune mediated neutropenia: Here, the immune system produces antibodies to immunoglobulins, which results in severe neutropenia.Acquired Neutropenias:
    • The most common cause of acquired neutropenia are infections.

 
 

  • Vitamin B12, folate, copper and low levels of other nutrients can cause neutropenia.

 
 

  • Many drugs and chemicals can be involved:

 

  • Medications for the thyroid gland, and certain types of antibiotics are most frequently involved.
  • Antibiotics include – cephalosporins, penicillin, gentamicin, clindamycin, trimethoprim and vancomycin.
  • Anti-inflammatory agents and pain killers such as – ibuprofen, acetylsalicylic acid and aminopyrine are involved.
  • Antidepressants and antipsychotics including phenothiazines (chlorpromazine), clozapine, risperidone, imipramine and desipramine may be seen to produce neutropenia.
  • Drugs for the thyroid gland include – carbimazole, thiouracil, propylthiouracil and methimazole.
  • Drugs involved with the heart – procainamide, propranolol, captopril, aprindine, hydralazine, methyldopa and nifedipine may be implicated.
  • Heavy metals such as gold and mercury should be considered.
  • Drugs used in cancer patients for chemotherapy & radiotherapy – Most chemotherapy agents are myelosuppressive, (they suppress bone marrow function) and thus production of white blood cells including neutrophils.

Progression of Neutropenia

If you have been diagnosed with neutropaenia, your body is more likely to develop bacterial infections. Prolonged neutropaenia also increases the risk of widepspread infection with fungi. Neutropaenia alone does not place you at increased risk of parasitic or viral infections.

Symptoms of Neutropenia

Patients with low levels of neutrophils can have many problems. If you are affected by this condition, there may be signs of infection such as fever (temperature above 38.5C), aches and pains, shortness of breath, productive coughing, chest pain, ear pain, sore throat, headache, etc. The lower the neutrophil count, the greater the risk of infection. Other symptoms may be a result of low levels of other cells that have been affected. This can produce anaemia symptoms such as tiredness, weakness and shortness of breath. If there are low platelets (cells which help the body’s blood to clot) there may be bruising and increased nose bleeds. It is important to remember that every person with neutropenia is unique and will experience different symptoms.
It may be important to tell your doctor what medications you are taking, as these may have an effect on the condition. A family history may reveal that some other people in your family experienced similar problems.
If you have had any tests done, the results of these tests should be obtained and passed on to the doctor. These results can help in telling the doctor how long your neutropenia has been going on for.

Clinical Examination of Neutropenia

People with neutropenia get many infections. During your examination, the doctor may find some signs of infections. Most infections occur in the mouth, lungs and skin.

  • Examination of the mouth area may reveal some signs of thrush (eg. white coating on tongue), gum infections and painful mouth ulcers.
  • Abnormal lumps, which may be enlarged glands may indicate spread of infection or, possibly, malignancy.
  • There may be some rashes, ulcers, or abnormal sores on your skin.
  • If needed, the area around your buttocks and rectum may be examined for sores, rashes or enlarged nodes.

How is Neutropenia Diagnosed?

The following tests may be ordered as the doctor sees appropriate:

The severity of neutropenia depends on the absolute neutrophil count (ANC) and is categorised as follows:

  • Mild – ANC of 1000-1500 cells per mm3.
  • Moderate – ANC falls between 500 – 1000 cells per mm3.
  • Severe – ANC falls below 500 per mm3.

 

  • In patients with fevers, the following tests may be obtained:
    • 2 sets of blood taken for cultures (a procedure to see if any organisms are grown in the blood).
    • Urine for investigation.
    • Chest x-ray – looking for signs of chest infections.
    • Sputum analysis – looking for any growths of organisms.

     

  • HIV testing may be carried out, if suspected in the patient.
  • If low levels of blood and low platelets are present, Vitamin B12 and folate levels may be obtained. Obtaining bone marrow from within our bones helps assess for any problems within the marrow.

    Prognosis of Neutropenia

    It is hard to predict what might happen to the patient with this condition. Infections obtained in people with low levels of neutrophils are usually severe and can be life threatening. Any sick patients with neutropenia should be treated with an antibiotic with a wide range of activity if there are any signs of infection.

    How is Neutropenia Treated?

    If you are affected by neutropenia, the doctor will provide supportive care such as oxygen, pain or fever relief and education. Care may vary depending on the cause, severity and duration of your neutropenia.
    Antibacterial (Antibiotic) Therapy:
    If you have neutropenia, you are more likely to become infected with a wide variety of bacteria. Antibiotic therapy targeting these bacteria should be started immediately if there are any signs of infection. You are susceptible to many bacteria normally found on the skin and in the bowel. There are a few rules that may guide your treatment:

    1. The doctor should give you antibiotics active against bacteria that could be causing your infection.
    2. The antibiotics used should target the bacteria commonly found in the hospital you are staying in.
    3. If you are already receiving antibiotics, the choice of subsequent antibiotics to treat any bacterial infections should target resistant organisms. Organisms known to cause infections in patients being treated with antibiotics already given should also be targeted.

    The initial antibiotic treatment should be reviewed on the basis of test results.
    Antifungal Therapy:
    If you are a cancer patient, fungal infections are most often associated with neutropenia. You are predisposed to the development of invasive fungal infections, most commonly those due to Candida and Aspergillus species.
    Conventionally, it has been common clinical practice to add an anti-fungal drug called Amphotericin B to treatment regimens, if a neutropenic patient continues to have a fever after 4 to 7 days of treatment. This is because it is difficult to grow fungi before the onset of widespread disease, which is associated with a high mortality.
    Fluconazole is another anti-fungal drug which has demonstrated efficacy against infections due to many Candida species. However it has no activity against some fungal species like Aspergillus. Newer anti-fungal drugs can target a wider spectrum of fungi (eg. Voriconazole), thus providing another option for the treatment of fungal infections.
    Antiviral Therapy:
    If you are a cancer patient, viral infections can cause large problems. There has been increasing availability of drugs with activity against Herpes group viruses. Serious infections due to Herpes viruses and Cytomegalovirus have been well documented, and Varicella Zoster virus (implicated in chicken pox and Shingles) infections may be fatal in patients receiving chemotherapy. Acyclovir is an antiviral drug that is well known, which can be used for treatment or prevention of infection.
    Other Therapeutic Modalities:
    Another option in treating your neutropenia is to replenish the amount of neutrophils in the body. Transfusing the cells that neutrophils are produced from helps treat some bacterial infections. However, this treatment is expensive and associated with side effects. This treatment is usually reserved for patients who are unresponsive to antibiotics.

    Neutropenia References

    1. Godwin JE, Shin JJ. Neutropenia 2005 E-medicine [serial online]. 2005 [cited 29th April 2006]. Available from URL: www.emedicine.com/MED/topic1640.htm
    2. Kasper DL. Harrisons Principles of Internal Medicine. New York: The McGraw-Hill Companies; 2006
    3. Kumar V, Abbas A K & Fausto N. Robbins & Cotran Pathologic Basis of Disease. China: Elseiver Saunders; 2005
    4. Kumar P, Clark M. Clinical Medicine United Kingdom: WB Saunders; 2002.
    5. Peakman M, Vergani D. Basic and Clinical Immunology: USA; Churchill Livingstone, 2000.