What is the cause of leukocytosis (elevated white blood cell count) in a 28-year-old male?

From the Guidelines

Leukocytosis in a 28-year-old male requires immediate attention to rule out life-threatening conditions such as leukemia, and the initial management should include a complete blood count with differential and targeted testing based on symptoms, with consideration of referral to hematology if the cause is unclear or if accompanied by anemia, thrombocytopenia, or abnormal cells on peripheral smear. The patient's symptoms, medical history, and medication use should be thoroughly evaluated to determine the underlying cause of leukocytosis. Common causes in a young adult include infection, inflammation, stress, medication effects, allergic reactions, or less commonly, hematologic disorders. If the patient has symptoms such as fever, chills, or localized pain, targeted testing should be performed including blood cultures, urinalysis, chest X-ray, or other imaging based on symptoms. For mild to moderate asymptomatic leukocytosis (WBC count <15,000/μL), watchful waiting with repeat CBC in 2-4 weeks may be appropriate, but for significant leukocytosis (>20,000/μL) or concerning symptoms, prompt evaluation is necessary 1.

If infection is suspected, empiric antibiotics may be started based on the likely source, with adjustment once culture results are available. Medications that commonly cause leukocytosis include corticosteroids, epinephrine, lithium, and some antibiotics, so medication review is important. In cases of hyperleukocytosis, defined as a WBC count more than 100 10^9/L, immediate medical treatment is required to prevent complications such as hemorrhagic events, tumor lysis syndrome, and infections, and hydroxyurea may be used to lower the WBC count, as recommended by the European LeukemiaNet 1.

Key considerations in the management of leukocytosis include:

• Thorough evaluation of symptoms, medical history, and medication use
• Targeted testing based on symptoms
• Referral to hematology if the cause is unclear or if accompanied by anemia, thrombocytopenia, or abnormal cells on peripheral smear
• Consideration of empiric antibiotics if infection is suspected
• Medication review to identify potential causes of leukocytosis
• Immediate medical treatment for hyperleukocytosis to prevent life-threatening complications.

From the FDA Drug Label

Hematological changes Isolated cases of agranulocytosis (< 500/mm3) have been reported, most of them after 10 days of treatment and following total doses of 20 grams or more. Other rarely observed adverse reactions (<0. 1%) include abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, biliary lithiasis, bronchospasm, colitis, dyspepsia, epistaxis, flatulence, gallbladder sludge, glycosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, a decrease in the prothrombin time, renal precipitations, seizures, and serum sickness

Leukocytosis is listed as a rarely observed adverse reaction (<0.1%) in the ceftriaxone drug label 2. This suggests that ceftriaxone may be associated with an increased white blood cell count in some patients. However, the exact incidence and clinical significance of this adverse reaction are not well established.

From the Research

Causes of Leukocytosis

• Leukocytosis can be caused by relatively benign conditions such as infections or inflammatory processes 3
• It can also be caused by primary bone marrow disorders, which are less common but more serious 3
• Physical stress, emotional stress, and certain medications such as corticosteroids, lithium, and beta agonists can also elevate white blood cell counts 3
• Increased eosinophil or basophil counts can lead to leukocytosis in some patients, resulting from various infections, allergic reactions, and other causes 3

Evaluation of Leukocytosis

• A thorough history, physical examination, and peripheral blood smear are the basis of the initial evaluation of leukocytosis 4
• Constitutional symptoms along with an abnormal peripheral blood smear result indicate the need for evaluation for malignancy 4
• 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 5
• The leukocyte differential may show eosinophilia in parasitic or allergic conditions, or it may reveal lymphocytosis in childhood viral illnesses 5

Symptoms and Referral

• Symptoms suggestive of a hematologic malignancy include fever, weight loss, bruising, or fatigue 5
• If malignancy cannot be excluded or another more likely cause is not suspected, referral to a hematologist/oncologist is indicated 5
• Urgent referral to a hematology subspecialist is indicated in cases of suspected acute leukemia 4
• White blood cell counts above 100,000 per mm3 (100 x 10(9) per L) represent a medical emergency because of the risk of brain infarction and hemorrhage 3

Other Considerations

• Leukocytosis can be a common sign of infection, particularly bacterial, and should prompt physicians to identify other signs and symptoms of infection 5
• Certain medications, asplenia, smoking, obesity, and chronic inflammatory conditions can also cause leukocytosis 5
• The presence of blasts is concerning for acute leukemia and may require bone marrow biopsy 6