What can cause neutropenia with a normal White Blood Cell (WBC) count?

From the Guidelines

Neutropenia with a normal White Blood Cell (WBC) count can be caused by several conditions, including certain medications such as antipsychotics, particularly clozapine, as well as viral infections, autoimmune disorders, bone marrow disorders, nutritional deficiencies, and genetic conditions. According to the study by 1, clozapine has significant side effects, including agranulocytosis, which occurs in approximately 1% of patients and is potentially fatal. This highlights the importance of monitoring blood cell counts in patients taking clozapine.

Some key points to consider when evaluating neutropenia with a normal WBC count include:

• Reviewing medications, such as antibiotics, chemotherapy drugs, and antipsychotics, which can cause neutropenia
• Checking for infections, such as viral or bacterial infections, which can also cause neutropenia
• Undergoing blood tests, including complete blood count with differential, vitamin levels, and sometimes bone marrow examination, to determine the underlying cause of neutropenia
• Considering autoimmune disorders, bone marrow disorders, nutritional deficiencies, and genetic conditions as potential causes of neutropenia

It's also important to note that the normal WBC count suggests that other white blood cell types, such as lymphocytes, monocytes, eosinophils, and basophils, are compensating for the low neutrophils, maintaining overall white cell numbers while neutrophil production or survival is specifically affected, as mentioned in the study by 1. Additionally, the study by 1 highlights the importance of preventing and treating cancer-related infections in patients with neutropenia.

In terms of specific conditions that can cause neutropenia with a normal WBC count, some examples include:

• Viral infections, such as HIV, hepatitis, or influenza
• Autoimmune disorders, such as lupus or rheumatoid arthritis
• Bone marrow disorders, including leukemia and myelodysplastic syndromes
• Nutritional deficiencies, such as vitamin B12 or folate deficiency
• Genetic conditions, such as cyclic neutropenia
• Ethnic neutropenia, which is common in people of African, Middle Eastern, or Mediterranean descent, representing a benign variation rather than a disease.

From the FDA Drug Label

Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia

Neutropenia can occur with a normal White Blood Cell (WBC) count due to a decrease in the absolute neutrophil count, which is a type of white blood cell. This can be caused by:

• Agranulocytosis: a potentially life-threatening reduction in white blood cells, including neutrophils 2
• Aplastic anemia: a condition where the bone marrow fails to produce enough blood cells, including neutrophils 2, 2, 3
• Bone marrow suppression: a condition where the bone marrow is unable to produce enough blood cells, including neutrophils, which can be caused by certain medications, including sulfamethoxazole and trimethoprim 2, 2, 3
• Other blood dyscrasias: a group of disorders that affect the blood and bone marrow, including neutropenia 2, 2

From the Research

Causes of Neutropenia with Normal WBC Count

• Neutropenia can occur with a normal White Blood Cell (WBC) count due to various reasons, including:
  • Benign ethnic neutropenia, which is a common condition in certain ethnic groups, particularly those of African descent, where individuals have consistently low absolute neutrophil counts without increased susceptibility to infection 4
  • Drug-induced immune neutropenia, where certain medications can cause the formation of antibodies against neutrophils, leading to their destruction 5
  • Pancytopenia, a condition characterized by a reduction in all blood cell types, including neutrophils, which can be caused by various factors such as vitamin deficiencies, drugs, or bone marrow failure syndrome 6
• In some cases, neutropenia can be masked by a normal WBC count, as the WBC count only provides a total count of all white blood cells, and not a specific count of neutrophils 7
• It is essential to consider the absolute neutrophil count (ANC) when evaluating neutropenia, as it provides a more accurate measure of the number of neutrophils in the blood 7

Factors Contributing to Neutropenia

• Certain medications, such as dipyrone, diclofenac, and ticlopidine, can increase the risk of neutropenia 5
• Vitamin deficiencies, such as vitamin B12 or folic acid deficiency, can also contribute to neutropenia 6
• Bone marrow failure syndrome, such as aplastic anemia, can lead to neutropenia due to impaired production of blood cells 6
• Ethnicity can also play a role in neutropenia, with certain ethnic groups being more prone to benign ethnic neutropenia 4