What is Agranulocytosis?
Neutrophils are a type of white blood cell that are very important in protecting our bodies from infection. Agranulocytosis is a serious condition where a person has dangerously low levels of neutrophils, fewer than 100 in each tiny drop of blood. This puts them at high risk of severe infection. This condition can be a result of inherited genetic issues or other acquired diseases. Signs of agranulocytosis may include fever, chills, or a sore throat. It’s a potentially deadly issue that requires quick diagnosis and treatment.
What Causes Agranulocytosis?
Agranulocytosis, a condition where the body has a low count of white blood cells, falls into two main categories, inherited and acquired. The inherited type is usually because of gene mutations in the molecule that builds neutrophils, a type of white blood cell. The most common mutations occur at a specific splice site within the gene. Acquired agranulocytosis can result from factors such as certain medications, chemicals, autoimmune diseases, and infections.
There is a list of common medications associated with this condition:
* Medicines used to treat cancer
* Pain relievers and anti-inflammatory drugs (gold, naproxen, and penicillamine)
* Medications for thyroid conditions (carbimazole, propylthiouracil)
* Drugs for irregular heartbeats (quinidine, procainamide)
* Blood pressure medications (captopril, enalapril, nifedipine)
* Antidepressants and other mental health drugs (clozapine, amitriptyline, dosulepin, mianserin)
* Drugs used to prevent or treat malaria (pyrimethamine, dapsone, sulfadoxine, chloroquine)
* Medicines for seizures (phenytoin, sodium valproate, carbamazepine)
* Antibiotics (sulphonamides, penicillin, cephalosporins)
Certain other medications (cimetidine, ranitidine, chloropropamide, zidovudine) may also be related to the condition.
Various infections have also been linked to agranulocytosis, including:
* Bacteria-related (typhoid fever, shigella enteritis, brucellosis, tularemia, tuberculosis)
* Rickettsial (a type of bacteria, causes conditions like rickettsialpox, human granulocytic anaplasmosis, Rocky Mountain spotted fever)
* Parasitic (kala-azar, malaria)
* Viruses (human immune deficiency, Epstein-Barr virus, cytomegalovirus, hepatitis viruses, human herpesvirus 6)
In addition, autoimmune conditions such as lupus and rheumatoid arthritis and bone marrow diseases like myelodysplastic syndrome and leukemia are often associated with agranulocytosis.
Risk Factors and Frequency for Agranulocytosis
Agranulocytosis is a rare medical condition that can occur at any age. Each year, there are between 6 and 8 cases for every million people. It’s been found that 70% of those cases are connected with the use of medication. Moreover, women are likely to experience it more often than men, possibly because women use more medication or have a higher rate of autoimmune diseases. The condition does not favor any race.
- Agranulocytosis is a rare condition that can affect people of all age groups.
- There are about 6 to 8 cases per million people each year.
- Approximately 70% of cases are associated with the use of medication.
- Women are more likely to develop agranulocytosis than men, possibly due to higher medication usage or increased prevalence of autoimmune diseases.
- The condition does not preferentially affect any particular race.
Signs and Symptoms of Agranulocytosis
Agranulocytosis is a condition often linked to the use of new medications, changes in medication, exposure to certain chemicals or physical agents, or recent infections. Individuals with this condition might also have a history of autoimmune diseases or a strong family history of frequent infections from early childhood onwards. The beginning symptoms of agranulocytosis usually include fatigue, fever, chills, or infections often presenting as ulcers, decaying gum lesions, or sore areas in the mouth. The condition might also manifest as a sore throat, issues with swallowing, and multiple skin abscesses. Agranulocytosis can begin suddenly, with sepsis as an initial presentation. Warning signs on examination typically include a high fever, a rapid heart rate, fast breathing, and low blood pressure.
- New or changed medication use
- Recent exposure to certain chemicals or physical agents
- History of autoimmune disease
- Family history of recurrent infections from early childhood
- Fatigue
- Fever
- Chills
- Mouth infections presenting as ulcers or lesions on gums or other areas of the mouth
- Sore throat with difficulty swallowing
- Multiple skin abscesses
- Sudden onset, potentially evidenced by sepsis
- High fever, usually over 40 degrees Celsius
- Rapid heart rate
- Fast breathing
- Low blood pressure
Testing for Agranulocytosis
Agranulocytosis is a health condition that requires a careful examination for diagnosis. The patient’s symptoms, use of medication, exposure to chemicals, and any recent infections are often taken into account. To begin the investigation, a doctor will typically order a complete blood count. This test counts the cells in the blood, and a diagnosis of agranulocytosis is made if there are less than 100 neutrophils (a type of white blood cell) in each microlitre of blood.
Also, the shape and structure of neutrophils are looked at in a blood smear test. A stain called Wright-stain is used to highlight these cells, which will most likely be scarce or completely absent in those suffering from agranulocytosis.
Several other tests may also be necessary, especially if the patient has a relevant medical history. These can include checks for the erythrocyte sedimentation rate, C-reactive protein, blood clotting factors, lactate dehydrogenase, antinuclear antibody, rheumatoid factor, liver and kidney function, and urine analysis. If the patient has a fever, the doctor may also test samples from the blood, urine, and sputum (mucus from the lungs), as well as from any other areas that might be infected.
Although imaging techniques can’t diagnose agranulocytosis, a chest X-ray may be taken as part of the initial investigation. If the blood smear test shows unusual results, the patient might need a bone marrow test, where a small sample of bone marrow is taken for examination.
Treatment Options for Agranulocytosis
Agranulocytosis, a serious condition where the body has a fewer number of white blood cells, needs immediate treatment. If the condition is thought to be caused by certain medications or substances, these should be stopped immediately, regardless of whether the patient is showing symptoms. This is because if the agranulocytosis is due to these substances, it is likely to improve between one and three weeks after the substance is stopped. In the meantime, general care actions such as maintaining good oral hygiene to avoid infection, controlling pain associated with mouth and gum lesions with gel, and using gargles can be beneficial. If the patient is suffering from constipation, stool softeners can help.
Certain medical substances can help speed up the production and effectiveness of white blood cells in the body. Filgrastim, sargramostim, and pegfilgrastim are some of the substances used in this case.
If there is an infection, antibiotics will be started immediately. These could include cefepime, different types of carbapenems like meropenem or imipenem-cilastatin, or piperacillin-tazobactam. In cases where the bacteria might be resistant, other drugs such as vancomycin or linezolid can be used. For example, linezolid or daptomycin can be used if the bacteria are resistant to vancomycin. Carbapenems can be used against certain types of gram-negative bacteria. In cases where the patient’s fever is not responding within four to five days or if the fever returns even when broad-spectrum antibiotics are given, antifungal coverage may be added. Examples of antifungals that may be used include amphotericin B, a broad-spectrum azole like voriconazole, or an echinocandin like caspofungin.
What else can Agranulocytosis be?
When a doctor suspects agranulocytosis, which is a very low count of white blood cells, they need to rule out several other conditions that affect your immune system or blood cells. These can include:
- Aplastic anemia: This is a condition where the bone marrow doesn’t make enough new blood cells. Signs can include feeling very tired, having pale skin, and experiencing unusual bleeding or bruising.
- Acute myeloid leukemia (AML) and Acute lymphoblastic leukemia (ALL): These are types of cancer that affect the bone marrow and blood. Signs are often similar to aplastic anemia, but can also include fevers, aches, and weight loss.
- Human immune deficiency virus (HIV): This is a virus that damages your immune system, making it harder for the body to fight off diseases and infections. Symptoms can range from flu-like illness and regular infections to more serious issues.
- Epstein-Barr virus (EBV) infectious mononucleosis: Also known as “mono” or “the kissing disease,” this condition makes you feel very tired and weak for weeks or even months. It also shows up with a sore throat, fever, and swollen glands.
- Bacterial sepsis: This is a potentially life-threatening condition where an infection spreads throughout the body. Its signs can include fever, chills, rapid breathing, and confusion.
Doctors will take a detailed medical history and run necessary tests to differentiate agranulocytosis from these conditions and come up with the best treatment plan.
What to expect with Agranulocytosis
There are several elements that can worsen the prognosis for patients suffering from agranulocytosis. These factors include:
* Being older than 65 years
* Having an absolute neutrophil count lower than 100/microlitre at the time of diagnosis
* Contracting serious concurrent infections such as septicemia or septic shock
* Having pre-existing medical conditions like kidney, heart, lung diseases, or systemic inflammatory diseases.
Possible Complications When Diagnosed with Agranulocytosis
Agranulocytosis is a condition where the risk of infection is significant, and the level of risk directly relates to the duration and severity of the condition. Specifically, if the count of a certain type of blood cells called ANC is less than 100 per microliter of blood for a period of 3-4 weeks, the chances of getting an infection is nearly 100%.
Sepsis, a condition where the body has an extreme response to an infection, is another major risk. With agranulocytosis, the body doesn’t have enough mature granulocytes, which are key cells involved in fighting infections. This makes it hard for the body to battle against infectious agents, increasing the chances of developing sepsis, a blood infection (bacteremia), or a more severe condition called septic shock. Septic shock is a serious medical condition brought on by an infection where abnormal metabolism and circulation occurs in the body, and it has a high mortality rate.
Preventing Agranulocytosis
When patients start a new medication, or change their existing one, that’s known to potentially cause a condition called agranulocytosis, it’s crucial that they understand this possible side effect. They should also know how important it is to have frequent blood tests, called CBC tests, when they first start taking the medication. These tests can help show whether a critical type of white blood cell, known as ANC, has dropped below a safe level. If this happens, it is essential to stop taking the medication that’s causing the issue, even if the patient isn’t showing signs of agranulocytosis.
Also, these patients should try to avoid coming into contact with people who have infections of the respiratory tract, steer clear of crowded places, and take protective measures when they must be in a crowd. This could include wearing a face mask and using hand sanitizer.
