What causes monocytopenia (low monocyte count)?

Causes of Monocytopenia (Low Monocyte Count)

Monocytopenia is most commonly caused by hematologic malignancies, bone marrow disorders, autoimmune conditions, severe infections, and certain medications that suppress bone marrow function.

Primary Causes of Monocytopenia

Hematologic Malignancies and Bone Marrow Disorders

• Myelodysplastic syndromes (MDS): Monocytopenia is present in approximately 29.5% of MDS patients and correlates with higher-risk disease categories and poorer prognosis 1
• Acute leukemias: Particularly B-lymphoblastic leukemia, where monocytopenia can be an important diagnostic clue even when circulating blasts are rare (≤1%) 2
• MonoMAC syndrome: A rare genetic immunodeficiency characterized by severe monocytopenia, NK- and B-lymphocytopenia, with risk of progression to MDS/AML 3

Autoimmune Disorders

• Systemic lupus erythematosus (SLE)
• Autoimmune lymphoproliferative syndrome
• Autoimmune cytopenias associated with chronic lymphocytic leukemia (CLL) 4

Infections

• Severe COVID-19 infection: Monocytopenia is observed in patients with severe infection and may be a marker for poor survival 5
• HIV infection
• Hepatitis C virus (HCV)
• Tuberculosis
• Other severe bacterial or viral infections

Medications and Treatments

• Chemotherapeutic agents
• Immunosuppressive drugs
• Certain antibiotics
• Radiation therapy: Acute radiation syndrome affects lymphocytes and monocytes at doses >1 Gy 4

Primary Immunodeficiencies

• DiGeorge syndrome
• Cartilage-hair hypoplasia
• Schimke syndrome
• Wiskott-Aldrich syndrome 4

Diagnostic Approach for Monocytopenia

Initial Evaluation

1. Complete blood count with differential to assess for isolated monocytopenia or pancytopenia
2. Peripheral blood smear examination to evaluate cell morphology
3. Review of medication history for potential bone marrow suppressants

Secondary Evaluation

1. Bone marrow examination: Essential when monocytopenia is persistent or associated with other cytopenias

   • Aspiration and biopsy to evaluate cellularity, dysplasia, and presence of abnormal cells
   • Flow cytometry to identify abnormal cell populations
   • Cytogenetic studies for suspected myeloid neoplasms 6, 4

2. Infectious disease workup:

   • HIV and HCV testing (recommended regardless of risk factors) 6
   • Testing for tuberculosis if clinically indicated

3. Autoimmune evaluation:

   • Antinuclear antibodies (ANA)
   • Antiphospholipid antibodies

Clinical Significance and Monitoring

• In MDS, monocytopenia is associated with lower overall survival (32.0 versus 65.0 months) and lower leukemia-free survival 1
• In COVID-19, developing or persistent monocytopenia is associated with severe disease and decreased survival time 5
• In pediatric patients with cytopenias, monocytes <1% by flow cytometry or absolute monocyte count <100 cells/μL may indicate occult leukemia even when peripheral blood flow cytometry is negative for blasts 2

Management Considerations

• Treatment should target the underlying cause of monocytopenia
• For MDS-associated monocytopenia, consider disease-modifying therapies based on risk stratification
• For medication-induced monocytopenia, consider dose adjustment or alternative medications when possible
• Monitor for infections, which may be more severe due to compromised innate immunity
• In cases of MonoMAC syndrome, consider evaluation for hematopoietic stem cell transplantation

Remember that monocytopenia can be an early warning sign of serious underlying conditions, particularly hematologic malignancies, and warrants thorough investigation when persistent or associated with other cytopenias.