What is agranulocytosis?

From the Guidelines

Agranulocytosis is a serious and potentially life-threatening blood disorder characterized by a severe reduction in the number of granulocytes, a type of white blood cell crucial for fighting infections. This condition occurs when the neutrophil count falls below 500 cells per microliter of blood, severely compromising the immune system 1. Agranulocytosis can develop as an adverse reaction to certain medications, including some antibiotics, antipsychotics, antithyroid drugs, and certain chemotherapy agents, as noted in guidelines for managing non-tuberculous mycobacterial pulmonary disease 1. It can also result from bone marrow disorders, autoimmune conditions, or severe infections. Patients with agranulocytosis typically experience symptoms such as:

• Fever
• Sore throat
• Mouth ulcers
• Recurrent infections that can rapidly become life-threatening Treatment usually involves immediately stopping the causative medication, administering broad-spectrum antibiotics for infections, and sometimes using granulocyte colony-stimulating factors like filgrastim to stimulate neutrophil production, as suggested by the management of subclinical thyroid disease 1. Regular blood monitoring is essential for patients taking medications known to cause this condition, as early detection can prevent serious complications. The body normally produces granulocytes in the bone marrow, but in agranulocytosis, this production is disrupted, leaving the body vulnerable to infections that would normally be controlled by these important immune cells. The most critical step in managing agranulocytosis is prompt recognition and intervention to prevent morbidity and mortality, emphasizing the importance of monitoring and early detection 1.

From the FDA Drug Label

Agranulocytosis occurs in approximately 0.2% to 0. 5% of patients and is a potentially life-threatening side effect of propylthiouracil therapy. Agranulocytosis typically occurs within the first 3 months of therapy. Agranulocytosis is the most serious effect. Inhibition of myelopoiesis (agranulocytosis, granulopenia, and thrombocytopenia), aplastic anemia, drug fever, a lupus-like syndrome (including splenomegaly and vasculitis), hepatitis, periartentis, and hypoprothrombinemia and bleeding have been reported.

Agranulocytosis is a potentially life-threatening side effect of propylthiouracil therapy, occurring in approximately 0.2% to 0.5% of patients, typically within the first 3 months of therapy. It is characterized by a decrease in the number of granulocytes, a type of white blood cell, in the blood. Patients should be instructed to immediately report any symptoms suggestive of agranulocytosis, such as fever or sore throat 2.

From the Research

Definition of Agranulocytosis

Agranulocytosis is a rare but serious complication of antithyroid drug therapy, characterized by a significant decrease in the number of granulocytes, a type of white blood cell, in the blood 3, 4, 5, 6, 7. This condition can lead to an increased risk of infection and can be life-threatening if left untreated.

Causes of Agranulocytosis

The exact cause of agranulocytosis is not fully understood, but it is thought to be related to the use of antithyroid drugs, such as methimazole and propylthiouracil, which are used to treat hyperthyroidism 3, 4, 5. Other factors, such as genetic predisposition and immune system disorders, may also play a role in the development of agranulocytosis.

Symptoms of Agranulocytosis

The symptoms of agranulocytosis can vary, but common signs include:

• Fever
• Sore throat
• Diarrhea
• Fatigue
• Weakness
• Pale skin
• Shortness of breath
• Chest pain 3, 4, 5, 6, 7

Diagnosis of Agranulocytosis

Agranulocytosis is typically diagnosed through a combination of physical examination, medical history, and laboratory tests, including:

• Complete blood count (CBC)
• Differential count
• Blood cultures
• Imaging studies, such as chest X-rays or computed tomography (CT) scans 3, 4, 5, 6, 7

Treatment of Agranulocytosis

Treatment for agranulocytosis typically involves:

• Discontinuation of the offending antithyroid drug
• Administration of broad-spectrum antibiotics
• Supportive care, such as hydration and oxygen therapy
• Granulocyte-colony stimulating factor (G-CSF) therapy to stimulate the production of white blood cells 3, 4, 5, 6, 7
• In some cases, total thyroidectomy may be necessary to control thyrotoxicosis 7