What is agranulocytosis
Agranulocytosis is an acute pathological condition that causes a severe reduction in white blood cells circulating in the blood. The result of this alteration determines, in particular, a deficiency of polymorphonuclear leukocytes (or granulocytes), a particular type of white blood cells that intervene in the defense of the organism.
In the presence of agranulocytosis, the concentration of granulocytes (neutrophils, basophils and eosinophils) falls to levels below 100 cells / mm³ of blood.
At the basis of agranulocytosis there may be an alteration of marrow myelopoiesis (the bone marrow fails to produce a sufficient number of granulocytes) or an increased destruction of these blood cells.
Acquired agranulocytosis occurs more often as a result of drug therapy, while the congenital form is present from birth.
The pathogenetic mechanisms of agranulocytosis can be determined by:
- Granulocyte production defects;
- Abnorme distribution;
- Reduced survival due to increased destruction (eg hypersplenism) or increased use (ie consumption, due to bacterial or viral infections).
Acquired agranulocytosis can be caused by a variety of factors, including:
- Autoimmune diseases;
- Tumors, inflammation, myelofibrosis and other bone marrow diseases;
- Aplastic anemia;
- Some drugs or treatments:
- Bone marrow transplant (or preparation for a bone marrow transplant);
- Drugs such as: rituximab, penicillin, captopril, ranitidine, cimetidine, methimazole and propylthiouracil;
- Cytostatic drugs such as clozapine or nitroxide.
Sometimes, agranulocytosis is present from birth. This condition can in fact be caused by some rather rare genetic alterations, which can be inherited from parents making it common within the same family.
The following factors increase the likelihood of developing agranulocytosis:
- Chemotherapy treatment for cancer;
- Taking some medications;
- Exposure to certain chemical toxins or radiation;
- Autoimmune diseases;
- Enlarged spleen;
- Vitamin B12 or folate deficiency;
- Leukemia or myelodysplastic syndrome;
- Aplastic anemia or other bone marrow diseases;
- Genetic predisposition.
Agranulocytosis may be asymptomatic, or may present clinically with sudden fever, chills and sore throat. Infection of any organ (pneumonia, infections of the urinary tract or skin) can be rapidly progressive and also develop into a septicemia. Agranulocytosis is also associated with gum disease.
The following symptoms may occur when suffering from agranulocytosis:
- Leukopenia (reduction in the number of circulating white blood cells);
- Fever, chills, muscle aches, weakness or sore throat;
- Bacterial pneumonia;
- Mouth ulcers;
- Bleeding gums, increased saliva, halitosis and destruction of the periodontal ligament;
- Fungal or bacterial infections.
Investigations that can help doctors diagnose agranulocytosis may include:
- Complete blood test to determine the granulocyte count;
- Urine or other biological samples can be analyzed to determine the presence of infectious agents;
- biopsy or needle aspiration of hematopoietic cord.
To formally diagnose agranulocytosis, other pathologies with a similar presentation must be excluded, such as myelodysplasia, leukemia and aplastic anemia. The differential diagnosis requires cytological and histological examination of the bone marrow, which shows an alteration of the promyelocytes, while other types of cells are present in normal values.
In some cases, more in-depth examinations may be required:
- Genetic tests;
- Dosage of anti-granulocyte autoantibodies in people with autoimmune diseases;
The treatment of agranulocytosis depends on the cause and the severity of the condition. In patients who do not have symptoms of infection, management consists of close monitoring with serial blood counts and elimination of the factor responsible for the primary disorder (for example, replacing a particular drug).
Treatment options include:
- Transfusion therapy
If necessary, the patient can undergo granulocyte transfusion. However, white blood cells tend to rapidly lose their functionality and the therapeutic effect produced is of short duration. Furthermore, there are many complications associated with this procedure.
- Antibiotic treatment
Some antibiotics may be prescribed to eradicate the causative agent of agranulocytosis or to prevent any infections that may be favored by leukopenia.
- G-CSF injection (stimulating factors)
Depending on the cause, some people may benefit from injections with granulocyte colony stimulating factor (G-CSF), in order to stimulate the marrow to produce more white blood cells. In case of agranulocytosis, the administration of recombinant G-CSF (filgrastim) often results in hematological recovery.
- Bone marrow transplant
In the most severe cases of agranulocytosis, a bone marrow (or stem cell) transplant may be necessary.