Agranulocytosis is a serious condition characterized by a dangerously low count of neutrophils, a specific type of white blood cell. This severe reduction significantly impairs the body’s ability to fight off infections, leaving individuals highly vulnerable to pathogens. The condition can arise from various factors, requiring prompt identification and management to prevent severe complications.
Understanding Agranulocytosis
Neutrophils are the most abundant type of white blood cell, playing a primary role in the body’s immune system. These cells act as first responders, quickly migrating to sites of infection to engulf and destroy invading microorganisms like bacteria and fungi. They are an important component of the innate immune response, providing defense against harmful agents.
Agranulocytosis is a severe deficiency where the absolute neutrophil count (ANC) drops below 100 cells per microliter of blood. This is much lower than general neutropenia, which is any abnormally low neutrophil level. When neutrophil levels are this low, the body’s primary defense mechanism is compromised, making even minor infections potentially life-threatening.
Causes and Risk Factors
Agranulocytosis has various causes, with drug-induced reactions being the most common, accounting for up to 70% of cases. Many medications can trigger this effect, including certain antipsychotics like clozapine, and antithyroid drugs such as methimazole and propylthiouracil. Antibiotics like trimethoprim/sulfamethoxazole and sulfasalazine, as well as some anti-inflammatory drugs, have also been implicated.
Drugs can interfere with neutrophil production in the bone marrow or lead to their rapid destruction, often through an immune-mediated mechanism. Beyond medications, autoimmune disorders such as lupus and rheumatoid arthritis can cause the immune system to attack neutrophils. Certain infections, including severe viral infections, malaria, or tuberculosis, may also suppress bone marrow activity.
Less commonly, underlying bone marrow diseases like aplastic anemia or leukemia can impair neutrophil production. Rare inherited conditions, such as Kostmann syndrome, prevent the bone marrow from producing enough neutrophils from birth. Exposure to specific chemicals or toxins can also damage bone marrow cells, reducing neutrophil counts.
Recognizing Symptoms and Complications
The symptoms of agranulocytosis are related to the body’s inability to fight infections. Individuals often experience a sudden onset of fever, chills, and a sore throat, indicating infection. Other common signs include painful mouth sores or ulcers, fatigue, and general malaise.
As the condition progresses, severe infection symptoms can emerge, such as rapid heart rate, accelerated breathing, and a drop in blood pressure. Minor cuts or abrasions may become infected, and skin abscesses can develop due to compromised immune defenses. With few infection-fighting cells, even common bacteria can lead to serious illnesses.
The main complication of agranulocytosis is the development of severe infections, leading to sepsis. Sepsis is a life-threatening systemic response to infection that can lead to organ damage and failure. The risk of such severe infections increases significantly if the neutrophil count remains dangerously low for an extended period.
Diagnosis and Management
Diagnosis begins with a complete blood count (CBC) with differential, which measures blood cell levels, including neutrophils. An absolute neutrophil count (ANC) below 100 cells per microliter indicates agranulocytosis. Further diagnostic steps may include a bone marrow examination to assess neutrophil production and to identify underlying causes like bone marrow disorders or genetic conditions.
Immediate management focuses on protecting the individual from infection and treating any existing infections. This involves the prompt administration of broad-spectrum antibiotics, even before the specific type of infection is identified, to cover potential bacterial pathogens. If a medication is suspected as the cause, discontinuing the offending drug is a primary intervention.
Supportive care measures are also important, including maintaining a sterile environment to minimize pathogen exposure. Granulocyte colony-stimulating factors (G-CSFs), such as filgrastim or pegfilgrastim, are often used to stimulate neutrophil production. These growth factors can help shorten the duration of severe neutropenia, reducing the risk of severe infections. In cases where an autoimmune disorder is the cause, immunosuppressive medications may modulate the immune response.