Agranulocytosis, also known as agranulosis, is an acute condition involving a severe and dangerous leukopenia, most commonly of neutrophils, causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells. People with this condition are at very high risk of serious infections due to their suppressed immune system.
In agranulocytosis, the concentration of granulocytes (a major class of white blood cells that includes neutrophils, basophils, and eosinophils) drops below 100 cells/mm³ of blood, which is less than 5% of the normal value. Agranulocytosis is more severe than granulocytopenia and may involve more sub-types of white blood cells than neutropenia.
The term derives from the Greek: a, meaning without; granulocyte, a particular kind of cell; osis, from the Greek, meaning condition [esp. disorder]. Consequently, granulocytosis is sometimes described as "no granulocytes", but a total absence is not required for diagnosis.
The terms agranulocytosis, granulocytopenia and neutropenia are sometimes used interchangeably. Agranulocytosis implies a more severe deficiency than granulocytopenia. Neutropenia indicates a deficiency of neutrophils (the most common granulocyte cell) only.
To be precise, neutropenia is the term normally used to describe absolute neutrophil counts (ANC) of less than 500 cells per microlitre, whereas agranulocytosis is reserved for cases with ANC of less than 100 cells per microlitre.
The following terms can be used to specify the type of granulocyte referenced:
- Inadequate numbers of neutrophils: neutropenia (most common)
- Inadequate numbers of eosinophils: eosinopenia (uncommon)
- Inadequate numbers of basophils: basopenia (very rare)
Signs and symptoms
Agranulocytosis may be asymptomatic, but may clinically present with sudden fever, rigors and sore throat. Infection of any organ may be rapidly progressive (e.g., pneumonia, urinary tract infection). Septicemia may also progress rapidly.
Neutropenia and agranulocytosis are associated with gum disease such as gingival bleeding, saliva increase, halitosis, osteoporosis, and destruction of periodontal ligament.
A large number of drugs have been associated with agranulocytosis, including antiepileptics, antithyroid drugs (carbimazole, methimazole, and propylthiouracil), antibiotics (penicillin, chloramphenicol and co-trimoxazole), cytotoxic drugs, gold, NSAIDs (indomethacin, naproxen, phenylbutazone), mebendazole, the antidepressant mirtazapine, and some antipsychotics (the atypical antipsychotic clozapine). Clozapine users in the US must be nationally registered for monitoring of low WBC and absolute neutrophil counts (ANC).
Although the reaction is generally idiosyncratic rather than proportional, experts recommend that patients using these drugs be told about the symptoms of agranulocytosis-related infection, such as a sore throat and a fever.
The diagnosis is made after a complete blood count, a routine blood test. The absolute neutrophil count in this test will be below 500, and can reach 0 cells/mm3. Other kinds of blood cells are typically present in normal numbers.
To formally diagnose agranulocytosis, other pathologies with a similar presentation must be excluded, such as aplastic anemia, paroxysmal nocturnal hemoglobinuria, myelodysplasia and leukemias. This requires a bone marrow examination that shows normocellular (normal amounts and types of cells) blood marrow with underdeveloped promyelocytes. These underdeveloped promyelocytes, if fully matured, would have been the missing granulocytes.
In patients that have no symptoms of infection, management consists of close monitoring with serial blood counts, withdrawal of the offending agent (e.g., medication), and general advice on the significance of fever.
Infection in patients with low white blood cell counts is usually treated urgently, and usually includes a broad-spectrum penicillin or cephalosporin (piperacillin-tazobactam, ceftazidime or ticarcillin clavulanate), or meropenem in combination with gentamycin or amikacin.
If the patient remains febrile after 4-5 days and no causative organism for the infection has been identified, antibiotics are, in general, changed to a glycopeptide (e.g., vancomycin), and subsequently an antifungal agent (e.g., amphotericin B) is added to the regimen. In agranulocytosis, the use of recombinant G-CSF (filgrastim) often results in hematologic recovery.
Transfusion of granulocytes would have been a solution to the problem. However, granulocytes live only ~10 hours in the circulation (for days in spleen or other tissue), which gives a very short-lasting effect. In addition, there are many complications of such a procedure.