What causes acute viral infections with neutropenia (low neutrophil count) and bicytopenia?

From the Guidelines

Acute viral infections with neutropenia and bicytopenia are primarily caused by reactivation of latent herpes viruses, such as varicella zoster virus (VZV) and cytomegalovirus (CMV), in patients with haematologic malignancies or solid tumours 1.

Causes of Acute Viral Infections

The main risk factor for clinically relevant reactivation is profound disruption of cellular immune response, with the duration and severity of neutropenia being of lesser importance 1.

• Reactivation of latent herpes viruses, such as VZV and CMV, is the primary cause of acute viral infections in patients with haematologic malignancies or solid tumours.
• Exogenous respiratory tract infections caused by influenza, parainfluenza, or respiratory syncytial virus (RSV) are less common.
• The risk of viral disease increases with the intensity and duration of functional T-cell suppression.

Management of Neutropenia and Bicytopenia

For neutropenia:

• Monitor complete blood count (CBC) regularly
• Maintain good hygiene to prevent secondary infections
• Consider granulocyte colony-stimulating factor (G-CSF) if severe (ANC <500/μL) or prolonged
• Dose: Filgrastim 5 μg/kg/day subcutaneously until neutrophil recovery For bicytopenia:
• Treat as above if neutropenia is present
• If anemia is present, consider transfusion if hemoglobin <7 g/dL or symptomatic
• If thrombocytopenia, transfuse platelets if count <10,000/μL or bleeding Antiviral treatment depends on the specific virus identified, such as:
• Influenza: Oseltamivir 75 mg twice daily for 5 days
• CMV: Ganciclovir 5 mg/kg IV every 12 hours for 14-21 days Most cases resolve as the viral infection clears, and persistent cytopenias warrant further investigation for underlying hematologic disorders 1.

Prevention of Viral Reactivation

Strategies for individual patient cohorts are based on their respective risk of viral reactivation or infection, and are outlined in the guidelines of the Infectious Diseases Working Party of the German Society for Hematology and Oncology 1.

• Patients with active malignant disease are at higher risk for upper respiratory tract infection due to influenza, parainfluenza, or RSV, and should receive immunoprophylaxis with the influenza vaccine.
• Patients with positive HBsAg or chronic hepatitis B, as well as patients who have already had an episode of HBV reactivation, should receive lamivudine 100 mg qd to prevent HBV reactivation.

From the FDA Drug Label

Cytopenias resulting from an antibody response to exogenous growth factors have been reported on rare occasions in patients treated with other recombinant growth factors.

The cause of acute viral infections with neutropenia (low neutrophil count) and bicytopenia is not directly stated in the provided drug label. However, it mentions that cytopenias, which include neutropenia, can result from an antibody response to exogenous growth factors, but this is related to treatment with other recombinant growth factors, not directly to acute viral infections. Key points:

• The label does not directly address the cause of acute viral infections with neutropenia and bicytopenia.
• Cytopenias can occur due to an antibody response to exogenous growth factors, but this is not directly related to the question. 2

From the Research

Causes of Acute Viral Infections with Neutropenia and Bicytopenia

• Viral infections can cause neutropenia, as seen in a case report of an 8-month-old male infant with autoimmune neutropenia associated with influenza virus infection 3.
• Neutropenia can also be caused by other factors, such as vancomycin therapy, which is an antibiotic commonly used for management of severe gram-positive infections 4.
• The risk of infection in immunocompromised patients is determined by the nature, degree, and duration of the immunosuppressive disease or therapy, and viral infections are predominantly associated with defects in cellular immune function 5.
• In adults with influenza A or B, neutropenia is common, with 15.3% of patients developing neutropenia, and the incidence is higher in association with influenza B than influenza A 6.
• In children, febrile neutropenia can be associated with invasive bacterial infection, but in otherwise healthy children and youth with fever and neutropenia, the risk for invasive bacterial infection is low, and most cases are caused by viral infections 7.

Bicytopenia

• Bicytopenia, which is a condition characterized by a reduction in two or more blood cell types, can be caused by vancomycin therapy, as seen in a case report of a 46-year-old woman who developed neutropenia, thrombocytopenia, and eosinophilia while on long-term vancomycin therapy 4.
• The mechanism of vancomycin-induced bicytopenia is poorly understood, but it is considered an immune-mediated phenomenon 4.
• Routine blood analysis during long-term vancomycin therapy is crucial to identifying hematologic suppression early, and prompt discontinuation of vancomycin is key to the management of the condition 4.