Symptoms
Typical symptoms of agranulocytosis include fever, chills, feeling ill, tonsillitis, sore throat, difficulty swallowing, and lesions and bleeding of the oral, nasal, pharyngeal, genital, or anal mucosa. The disease can lead to dangerous infections and blood poisoning and, if left untreated, can relatively often be fatal. Agranulocytosis usually occurs rarely to very rarely as a side effect of medications.
Causes
Agranulocytosis manifests as a severe drop in the number of granulocytes in the bloodstream (number <500 per µl). Granulocytes are white blood cells (leukocytes) that play a central role in immune defense. A distinction is made between neutrophils, basophils and eosinophils. Agranulocytosis can be triggered by various drugs through immunogenic or cytotoxic mechanisms. The best known risk drugs include clozapine, metamizole, the thyrostatic drugs and sulfasalazine. The following list shows a selection of agents that can cause agranulocytosis as an adverse effect. The original drugs are shown in parentheses. Generic drugs are also available:
- Clozapine (Leponex).
- Diclofenac (Voltaren)
- Fluconazole (Diflucan)
- Furosemide (Lasix)
- Infliximab (Remicade)
- Lamotrigine (Lamictal)
- Levamisole (used for stretching illicit cocaine).
- Metamizole (Novalgin, Minalgin).
- Mianserin (Tolvon)
- Penicillamine (out of trade)
- Penicillins
- Phenylbutazone (out of trade)
- Spironolactone (Aldactone)
- Sulfasalazine (Salazopyrin)
- Terbinafine (Lamisil)
- Thyrostatic agents: Carbimazole (Néo-Mercazole), propylthiouracil (Propycil), thiamazole (D).
- Ticlopidine (out of trade).
- Trimethoprim and sulfamethoxazole (Bactrim).
- Vancomycin (Vancocin)
- Cytostatics
Diagnosis
If the symptoms described occur while taking high-risk medications, patients and professionals should think of agranulocytosis. Diagnosis is made under medical care on the basis of symptoms, physical examination, and with blood testing. Other possible causes must be excluded.
Prevention and early detection
Patients should be informed of the risk and possible symptoms before starting and during treatment. If appropriate disorders occur, they should seek medical treatment.
- Patients who have already experienced agranulocytosis on any drug should not receive it.
- Whenever possible, high-risk drugs should be administered as second-line agents and only for approved indications.
For high-risk medications such as clozapine, additional blood count monitoring is required. When levels drop, therapy is discontinued.
Treatment
The offending drug is identified and promptly discontinued. Parenteral antibiotics are administered for treatment. Hospitalization is usually necessary. The use of G-CSF such as filgrastim is mentioned in the literature.
Appendix for Health Care Professionals
Patient Information Template: “This drug can rarely cause a life-threatening change in the blood count. Typical symptoms include:
- Fever, chills
- Feeling sick
- Tonsillitis
- Sore throat
- Mucosal changes
Seek medical attention immediately if such symptoms occur.”
