What is the cause of an elevated white blood cell (WBC) count in the absence of infection, accompanied by mild anemia?

From the Guidelines

An elevated white blood cell count without infection, accompanied by mild anemia, warrants immediate medical evaluation to rule out underlying bone marrow disorders, such as myeloproliferative neoplasm or leukemia, as suggested by recent guidelines 1. This combination of findings may indicate a reactive process like inflammation or stress response, and it is crucial to characterize the specific white cell elevation pattern. I recommend a complete blood count with differential, along with peripheral blood smear examination, to guide further testing and management. Additional testing should include inflammatory markers (ESR, CRP), iron studies, vitamin B12 and folate levels, and possibly bone marrow examination depending on initial results, as outlined in the guidelines for myelodysplastic syndromes 1. These abnormalities warrant prompt follow-up with a hematologist, especially if symptoms like fatigue, unexplained fever, night sweats, weight loss, or easy bruising are present, which can be indicative of chronic myeloid leukemia, as described in the ESMO clinical practice guidelines 1. The white blood cell elevation may represent a reactive leukocytosis due to stress, medications (like corticosteroids), or underlying inflammatory conditions, while anemia could result from chronic disease, nutritional deficiencies, or bone marrow dysfunction, as discussed in the context of cancer- and chemotherapy-induced anemia 1. The relationship between these findings is important as they may represent different manifestations of a single underlying disorder affecting blood cell production. Key considerations in the management of these patients include:

• Regular monitoring of blood counts to detect worsening cytopenias
• Prompt initiation of broad-spectrum antibiotics in case of symptoms of infection
• Bone marrow examination, with or without karyotype, triggered by worsening of cytopenias or the appearance of circulating blasts
• Referral to a hematologist for further evaluation and management, as emphasized in the guidelines for myelodysplastic syndromes 1 and chronic myeloid leukemia 1.

From the FDA Drug Label

Hydroxyurea causes severe myelosuppression. Treatment with hydroxyurea should not be initiated if bone marrow function is markedly depressed. Bone marrow suppression may occur, and leukopenia is generally its first and most common manifestation. Thrombocytopenia and anemia occur less often and are seldom seen without a preceding leukopenia Bone marrow depression is more likely in patients who have previously received radiotherapy or cytotoxic cancer chemotherapeutic agents; use hydroxyurea cautiously in such patients. Evaluate hematologic status prior to and during treatment with hydroxyurea capsules. Provide supportive care and modify dose or discontinue hydroxyurea as needed.

The patient has an elevated white count in the absence of infection and is a little bit anemic. Hydroxyurea can cause myelosuppression, which may lead to leukopenia, thrombocytopenia, and anemia.

• The elevated white count may not be directly related to hydroxyurea, as hydroxyurea typically causes leukopenia.
• The anemia could be related to hydroxyurea, as it is a known side effect of the medication. It is essential to monitor hematologic status and modify the dose or discontinue hydroxyurea as needed to minimize the risk of further myelosuppression 2.

From the Research

Elevated White Count and Anemia

• An elevated white blood cell count can have various causes, including malignant and nonmalignant conditions 3.
• In the absence of infection, other potential causes of leukocytosis should be considered, such as stress, certain medications, or chronic inflammatory conditions 3, 4.
• Anemia can be a concurrent finding with leukocytosis, and its presence may suggest a underlying bone marrow disorder or other conditions such as myeloproliferative neoplasms 5, 6.

Diagnostic Approach

• A repeat complete blood count with peripheral smear may provide helpful information, such as types and maturity of white blood cells, uniformity of white blood cells, and toxic granulations 3.
• The leukocyte differential may show eosinophilia or lymphocytosis, which can help narrow down the potential causes of leukocytosis 3, 7.
• A bone marrow biopsy may be necessary to diagnose certain conditions, such as myeloproliferative neoplasms or primary bone marrow disorders 5, 4.

Potential Causes

• Myeloproliferative neoplasms, such as polycythemia vera or essential thrombocythemia, can cause leukocytosis and anemia 5.
• Reactive leukocytosis can occur in response to stress, infection, or inflammation, and can be distinguished from malignant leukocytosis through examination of the peripheral blood smear and other diagnostic tests 4, 7.
• Other potential causes of leukocytosis and anemia include chronic inflammatory conditions, certain medications, or bone marrow disorders such as leukemia or lymphoma 3, 6.