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Agranulocytosis: Causes, Symptoms and Treatment

Agranulocytosis is a severe deficiency of neutrophil granulocytes in the blood, which critically weakens the immune system and can cause life-threatening infections.

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Things worth knowing about "Agranulocytosis"

Agranulocytosis is a severe deficiency of neutrophil granulocytes in the blood, which critically weakens the immune system and can cause life-threatening infections.

What is Agranulocytosis?

Agranulocytosis is a serious blood disorder characterized by an extreme reduction or complete absence of neutrophil granulocytes – a critical type of white blood cell. Neutrophils are a key component of the human immune system and play an essential role in defending the body against bacterial and fungal infections. A severe deficiency of these cells leaves the body almost defenseless against pathogens and can rapidly lead to life-threatening conditions.

Medically, agranulocytosis is defined as a neutrophil count below 500 cells per microliter of blood. When levels fall below 100 cells per microliter, the condition is considered especially dangerous.

Causes

Agranulocytosis can arise from various causes. A fundamental distinction is made between drug-induced and non-drug-induced forms.

Drug-Induced Agranulocytosis

This is the most common cause. Certain medications can inhibit the production of granulocytes in the bone marrow or trigger an immune-mediated destruction of these cells. Drug groups most frequently involved include:

Antipsychotics (e.g., clozapine)
Antithyroid drugs (e.g., methimazole, propylthiouracil)
Antibiotics (e.g., cotrimoxazole, chloramphenicol)
Non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., metamizole)
Cytostatic agents (cancer medications)

Other Causes

Autoimmune diseases (e.g., systemic lupus erythematosus)
Viral infections (e.g., Epstein-Barr virus, HIV)
Bone marrow disorders (e.g., aplastic anemia, leukemia)
Severe sepsis
Congenital forms (e.g., severe congenital neutropenia)

Symptoms

The symptoms of agranulocytosis primarily result from the loss of immune defense. Since the body is no longer able to effectively fight pathogens, severe infections develop rapidly. Typical signs include:

High fever (often the first warning sign)
Chills and rigors
Severe sore throat and inflammation of the oral mucosa (mucositis)
Ulcers in the mouth and throat area
General weakness and fatigue
Rapidly progressing infections of the skin, lungs, or other organs
In the worst case: sepsis (blood poisoning)

Important note: Because the inflammatory response is severely impaired, typical signs of infection (e.g., pus formation) may be absent or very mild.

Diagnosis

Agranulocytosis is diagnosed through a blood test using a differential blood count, which identifies and quantifies the different types of white blood cells. A diagnosis is confirmed when neutrophil counts are found to be critically low.

To determine the underlying cause, additional investigations may be required:

Bone marrow biopsy (to assess blood cell production)
Testing for autoantibodies
Virological testing
Detailed medication history (review of all current and recent drugs)

Treatment

Treatment of agranulocytosis depends on the underlying cause and the severity of the condition.

Immediate Measures

Discontinuation of the causative drug (if drug-induced)
Hospital admission
Protective measures against infection (isolation, strict hygiene protocols)

Medical Therapy

Broad-spectrum intravenous antibiotics in the presence of fever or signs of infection
G-CSF (granulocyte colony-stimulating factor): medication to stimulate granulocyte production in the bone marrow (e.g., filgrastim)
Antifungal therapy in case of fungal infections
In severe cases: bone marrow transplantation

When detected early and treated promptly, the prognosis for agranulocytosis is favorable in many cases. However, without treatment, the condition can become life-threatening very quickly.

References

Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Annals of Internal Medicine, 2007; 146(9): 657-665.
Kaufman DW, Kelly JP, Levy M, Shapiro S. The Drug Etiology of Agranulocytosis and Aplastic Anemia. Oxford University Press, 1991.
Dale DC. How I manage patients with neutropenia. British Journal of Haematology, 2023; 200(3): 264-275.

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