Neutropenia and drug-induced agranulocytosis !

Too few neutrophils, the white cells that fight bacteria. When a medicine wipes them out almost completely, a simple sore throat can turn into sepsis.

Updated 2026-11-01

Structures involved

Tap one to see what it is and open it in 3D.

Why it happens

What it is

Neutropenia is an absolute neutrophil count (ANC) below the normal range, usually under 1500 cells/µL in adults; it is severe below 500/µL. Agranulocytosis is the near-total absence of neutrophils, most often an idiosyncratic reaction to a non-chemotherapy drug, and is a medical emergency because of the risk of overwhelming infection.

Who gets it

Chemotherapy is the commonest cause of neutropenia overall. Idiosyncratic drug-induced agranulocytosis is rare, affects older adults and women more often, and usually starts within the first weeks to three months of a new drug. In Latin America, including Colombia, metamizole (dipyrone), an analgesic sold widely without restriction, is a classic culprit alongside antithyroid drugs and clozapine. Some people of African or Middle Eastern descent have a lifelong mild, harmless low count (Duffy-null associated neutrophil count).

Causes

Non-chemotherapy drugs: antithyroid drugs (methimazole, propylthiouracil), clozapine, metamizole, sulfonamides and sulfasalazine, some beta-lactams, carbamazepine, ticlopidine, dapsone
Cytotoxic chemotherapy and immunosuppressants (predictable, dose-related marrow suppression)
Infections: viral (EBV, HIV, hepatitis, dengue), severe sepsis, tuberculosis, typhoid, malaria and leishmaniasis
Nutritional: vitamin B12, folate or copper deficiency
Marrow failure or infiltration: aplastic anaemia, leukaemia, myelodysplasia, metastatic cancer
Immune destruction: autoimmune neutropenia, lupus, Felty syndrome (rheumatoid arthritis with splenomegaly), large granular lymphocyte leukaemia
Congenital forms: severe congenital neutropenia and cyclic neutropenia (ELANE mutations)

Risk factors

Starting a high-risk drug in the previous three months
Older age and female sex
Previous reaction to the same drug (re-exposure can cause a rapid relapse)
Kidney failure, which raises drug levels
Autoimmune disease or splenomegaly

Pathophysiology

Neutrophils live only hours in the blood, so any fall in marrow output or rise in destruction shows up quickly. Drugs act in two ways: some act as haptens on the neutrophil surface and trigger antibodies that destroy mature cells within days, while others, or their reactive metabolites, are directly toxic to myeloid precursors after weeks of use. Without neutrophils the body cannot contain bacteria and fungi from the mouth, gut and skin; pus and local inflammation are reduced, so infections spread with few signs other than fever. Infection risk rises sharply below 500/µL and is highest below 100/µL.

Classification

Mild: ANC 1000–1500/µL
Moderate: ANC 500–1000/µL
Severe: ANC below 500/µL
Agranulocytosis: ANC below 100–500/µL, usually drug-induced
By mechanism: reduced production, peripheral destruction, or pooling (margination, splenic sequestration)

Symptoms and signs

Often no symptoms until an infection appears
Sudden high fever, chills and malaise
Severe sore throat, painful swallowing and mouth ulcers
Gum inflammation and recurrent skin or perianal infections
Pneumonia or sepsis in severe cases

Diagnosis

Clinical: Suspect it in any febrile patient taking a high-risk drug. Ask about every medicine started in recent months, including over-the-counter analgesics, and look for oral ulcers, pharyngitis, skin and perianal infection. Neutropenic patients may have pneumonia without much on the chest X-ray and infection without pus.
Tests: Full blood count with differential to calculate the ANC, and a blood smear. Blood and urine cultures before antibiotics when there is fever. Repeat counts after the drug is stopped. If the cause is not clear: vitamin B12, folate and copper levels, HIV and hepatitis serology, antinuclear antibodies, and bone marrow aspirate and biopsy (marrow typically shows absent mature myeloid cells with preserved earlier precursors in drug reactions).
Imaging: Chest X-ray or CT and other imaging guided by the suspected site of infection; abdominal ultrasound for splenomegaly.

Differential diagnosis

Chemotherapy-induced (febrile) neutropenia
Aplastic anaemia
Acute leukaemia or myelodysplastic syndrome
Viral or severe bacterial infection with transient neutropenia
Duffy-null associated (benign ethnic) neutropenia
Hypersplenism and Felty syndrome

Goal of treatment

Remove the cause, treat infection fast and protect the patient until the neutrophil count recovers.

Treatment

Acute: Stop the suspected drug at once and do not restart it or drugs of the same class; record the reaction as an allergy.
Acute: Fever with severe neutropenia is treated as an emergency: cultures, then empiric broad-spectrum intravenous antibiotics within the first hour, with antifungals if fever persists.
Medical: Granulocyte colony-stimulating factor (G-CSF) may shorten recovery in severe agranulocytosis; treat underlying causes such as vitamin deficiency or autoimmune disease.
Follow-up: Counts usually recover one to three weeks after the drug is stopped. Clozapine requires regular ANC monitoring by protocol; patients on antithyroid drugs are taught to stop the drug and get a blood count if fever or sore throat appears.
Follow-up: Nursing care: neutropenic precautions with strict hand hygiene, avoiding rectal temperatures and enemas, daily inspection of mouth, skin and catheter sites, oral hygiene, frequent vital signs and early report of any fever.

Drugs for this condition

Filgrastim

Complications

Sepsis and septic shock
Pneumonia, pharyngeal and deep neck infections
Perianal abscess and neutropenic enterocolitis
Invasive fungal infection with prolonged neutropenia
Death, reported in up to about one in five cases of drug-induced agranulocytosis

Prognosis

Drug-induced agranulocytosis usually reverses fully when the drug is stopped and infections are treated early; mortality is higher in older patients, with kidney failure or septic shock. Congenital and marrow-failure forms depend on the underlying disease.

Prevention

Avoiding unnecessary use of high-risk drugs such as metamizole
Teaching patients on antithyroid drugs or clozapine to report fever or sore throat immediately
Scheduled blood count monitoring where protocols require it
Never re-exposing a patient to a drug that caused agranulocytosis

Test yourself

Think of the answer, then tap the question to see it.

A woman on methimazole for Graves disease develops fever and a sore throat. What is the first step?

Stop methimazole and check a full blood count with differential urgently; if the ANC is very low, give empiric broad-spectrum antibiotics.

Which antipsychotic requires mandatory regular neutrophil count monitoring?

Clozapine, because of its risk of agranulocytosis.

What ANC defines severe neutropenia?

An absolute neutrophil count below 500 cells/µL.

Which widely used analgesic in Latin America is a classic cause of agranulocytosis?

Metamizole (dipyrone).

What is a key nursing precaution for a patient with severe neutropenia?

Strict hand hygiene with no rectal temperatures or enemas, and immediate report of any fever.

Add to my cards (5)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: Agranulocytosis (MedlinePlus (U.S. National Library of Medicine), 2026); Acute Iatrogenic Agranulocytosis: A Rare and Dire Case of an Adverse Drug Reaction to Be Aware (Case Reports in Hematology (PubMed Central), 2020).

← All conditions

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.

Sternum highlighted on the Durgical 3D model