Introduction:
Neutrophils are leukocytes (white blood cells) that help fight against infections and injuries. They act as the first line of defense in protecting the body against disease-causing organisms. Generally, WBC (white blood cells) are divided into granulocytes and agranulocytes. Eosinophils, basophils, and neutrophils constitute granulocytes, lymphocytes, and monocytes together constitute agranulocytes. These neutrophils catch and engulf the disease-causing microorganisms entering the body. The primary function of neutrophils is tissue repair and wound healing.
What Is Neutropenia?
For the normal functioning of the body, the neutrophil count should remain in a specific range, the absolute neutrophil count (ANC) in a healthy person should range from 2500 to 6000 cells per cubic millimeter of blood, but in certain conditions, the neutrophils count may differ, any condition that causes the infection-fighting neutrophils count to fall less than 500 cells per cubic millimeter of blood is known as neutropenia. Neutropenia is a fatal condition mainly because of chemotherapy (a type of cancer treatment), certain infections, autoimmune diseases, and certain medications. Too low a neutrophil count causes the loss of defense mechanisms, and the body is prone to repeated infections.
What Is Drug-Induced Neutropenia?
Drug-induced neutropenia is a life-threatening condition that occurs mainly because of the low count of neutrophils. Usually, neutropenia arises mainly because of two conditions, namely:
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Decreased Production of Neutrophils: Decreased production of neutrophils is usually seen in cancer-suffering people receiving chemotherapy (cancer treatment by using medication). These chemotherapeutic drugs suppress the myeloid progenitor cells in the bone marrow. These myeloid progenitor cells are considered precursors of RBC (red blood cells), granulocytes (neutrophils, basophils, acidophils), monocytes, and platelets. Hence the suppression of myeloid cells causes decreased production of neutrophils.
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Increased Destruction of Neutrophils: Increased destruction of neutrophils is caused by idiosyncratic (peculiar or particular) responses to certain types of drugs (non-chemotherapeutic drugs).
What Are The Common Non-Chemotherapeutic Drugs That Cause Neutropenia?
Various drugs are known to induce neutropenia, but the common drugs include:
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Antipsychotic Drugs: Drugs such as Clozapine are used to treat schizophrenia (a chronic brain disorder that results in loss of thinking, disability, hallucinations, and delusions). Patients who are receiving Clozapine are at the highest risk of developing neutropenia, and hence frequent monitoring is necessary for these patients. The depletion of neutrophils is mainly because of the neutrophils' apoptosis (organized cell death).
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Drugs Used in the Treatment of Rheumatoid Arthritis: Levamisole, Sulfasalazine are the drugs of choice in the treatment of inflammatory conditions such as rheumatoid arthritis (autoimmune disease mainly attacking the joints and causing pain), nephrotic syndrome (kidney disorder), Crohn’s disease (inflammatory disease of the gastrointestinal tract), and ulcerative colitis (an immune-related condition causing ulcers in the inner lining of large intestine). Agranulocytosis (decreased count of granulocytes such as neutrophils, basophils, and acidophils) is usually seen in people using Levamisole and Sulfasalazine. Neutrophil autoantibodies (antibodies that are produced against the person’s neutrophils) are the main cause of neutropenia in these patients.
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Vancomycin Therapy: Antibiotic Vancomycin therapy is generally used to treat gram-positive bacterial infections. Vancomycin initiates antibody-mediated destruction of neutrophils leading to neutropenia. Neutropenia gets reversed once the patient discontinues the drug.
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Hyperthyroidism: Methimazole, Carbimazole, and Propylthiouracil used in treating hyperthyroidism are known to cause neutropenia. These drugs act by decreasing the amount of thyroid hormone levels in the body. Anti-neutrophil antibodies are the cause of neutropenia in these drug users.
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Narcotic Drugs: Narcotic drugs such as Cocaine and Heroin are also known to cause neutropenia.
What Are Chemotherapeutic Drugs That Cause Neutropenia?
Neutropenia caused due to non-chemotherapeutic drugs is less common when compared to chemotherapeutic drugs. Chemotherapeutic drugs that cause neutropenia include:
Rituximab: This is a monoclonal antibody exclusively used in the treatment of malignant conditions such as non-hodgkin’s lymphoma (cancer of leukocytes), chronic lymphocytic leukemia (cancer of blood and bone marrow), and follicular lymphoma (cancer that starts in the B lymphocytes which are considered as fighting cells against infection). Rituximab is also prescribed for certain inflammatory conditions such as rheumatoid arthritis. Depending on the clinical manifestations, Rituximab can be used singly or in combination with other chemotherapeutic drugs. Rituximab is known to cause severe neutropenia leading to fevers that require hospitalization. Neutropenia occurs within 10 to 14 days following the Rituximab administration and occurs after every treatment cycle. The neutrophil recovery takes about 21 to 28 days to reach its original count.
How to Treat Chemotherapeutic Drug-Induced Neutropenia?
Prolonged neutropenia that occurs because of Rituximab leads to severe infectious complications such as fever, sore throat, skin, and soft tissue infections. These complications could be managed by using the following drugs
1. Antimicrobial Drugs: Cefepime, Ceftazidime, Meropenem, and Imipenem are antimicrobial drugs used to treat drug-induced infections.
2. G-CSF (Granulocyte Colony Stimulating Factors: Granulocyte-colony stimulating factors is a growth factor prescribed after chemotherapy to replace white blood cells. After certain cancer treatments, patients are more prone to infections because of the decreased amount of white blood cells. G-CSF helps in the increased production of white blood cells that help in fighting against disease-causing bacteria, and it also helps in the movement of stem cells from the bone marrow to blood circulation. G-CSF is induced intravenously or as an injection underneath the skin. Different types of G-CSF include:
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Filgrastim: A synthetic drug that helps prevent neutropenia after cancer treatments.
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Lenograstim: This is a granulocyte colony-stimulating factor that helps in the stimulation of the production of neutrophils. This also mobilizes the neutrophils from the bone marrow into the bloodstream.
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Pegylated Filgrastim (Long-Acting Drug): This drug, also called Pegfilgrastim, is considered a long-acting type of Filgrastim. The long-lasting action of pegylated agents is mainly because of heat resistance, resistance against enzyme activity, prolonged shelf-life, and stability in plasma concentrations. This long-lasting Pegfilgrastim is indicated in breast cancer (seen in women where the cells in the breast grow out of control), lung cancers (cancer that begins in the lungs), non-hodgkin’s lymphoma (cancer that attacks the white blood cells which play an important role in the defense mechanism of the body).
3. Blood Transfusions: Granulocyte concentrates are used in blood transfusion in severe infections. Recurrent reinfusion and the short granulocyte span have decreased the granulocyte transfusion rate.
Along with the above treatments, patients are also advised to maintain proper personal hygiene, brush their teeth regularly, and use stool softeners to reduce the strain during defecation. These measures help in the prevention of infections.
Conclusion:
Drug-induced neutropenia (low count of neutrophils) is a life-threatening condition that occurs secondary to using certain drugs. Drug-induced neutropenia is commonly seen among cancer patients who are undergoing chemotherapy. Non-chemotherapeutic drugs such as Clozapine, Levamisole, and certain antibiotics also cause neutropenia. In most cases, neutropenia is reversed by discontinuing the drug known to cause neutropenia.
