Leukocytosis
Susan R. Rheingold, MD
Leukocytosis - BASICS
Leukocytosis - description
An increase in WBC count above normal for age
Leukocytosis - risk factors
- Allergic disorders
- Hematologic disorders
- Immunodeficiencies
- Inflammatory disorders
- Malignancy
- Rheumatologic diagnoses
Leukocytosis - pathophysiology
Most frequent cause is an increase in the total neutrophil count, but leukocytosis may result from an increase in any type of WBC, such as lymphocytosis, monocytosis, eosinophilia, or basophilia.
Leukocytosis - etiology associated-conditions
- Causes of neutrophilia:
- Bacterial infections
- Inflammatory states
- Acute hemorrhage
- Stress
- Drugs: Corticosteroids, epinephrine
- Metabolic disorders: Uremia, acidosis
- Myeloproliferative disorders: Myelofibrosis, polycythemia vera, chronic myelogenous leukemia
- Sickle cell disease
- Causes of lymphocytosis:
- Viral infections: Cytomegalovirus, Epstein-Barr virus, pertussis, hepatitis, toxoplasmosis
- Acute infectious lymphocytosis
- Chronic infections: Tuberculosis, brucellosis
- Syphilis
- Malignancy: Acute lymphoblastic leukemia, lymphoma
- Relative lymphocytosis: Addison disease, thyrotoxicosis, splenic sequestration
- Causes of eosinophilia:
- Allergic disorders: Asthma, urticaria, drug hypersensitivity
- Skin disorders: Eczema, psoriasis, pemphigus
- Parasitic infections
- Fungal infections
- Immunologic disorders: Rheumatoid arthritis, systemic lupus erythematosus, eosinophilia–myalgia syndrome
- Malignancies: Non-Hodgkin lymphoma, Hodgkin disease
- Myeloproliferative disorders: Chronic myelogenous leukemia, polycythemia vera, myelofibrosis
- Hypereosinophilic syndromes
- Hereditary eosinophilia
- Hematologic disorders: Fanconi anemia, thrombocytopenia with absent radii
- Congenital neutropenias
- Inflammatory disorders: GI, sarcoidosis, polyarteritis nodosa
- Causes of monocytosis:
- Infection
- Tuberculosis
- Malaria
- Brucellosis
- Bacterial endocarditis
- Inflammatory disease
- Collagen vascular disease
- Sarcoid
- Rheumatoid arthritis
- Crohn disease, ulcerative colitis
- Systemic lupus erythematosus
- Malignancy
- Hodgkin disease
- Acute myelocytic leukemia
- Myelodysplastic syndromes
Leukocytosis - DIAGNOSIS
Leukocytosis - signs & symptoms
- Phase 1: Which WBC line is elevated?
- Elevated neutrophil count is more likely with bacterial infections; lymphocytosis is usually associated with viral infections.
- Eosinophilia often indicates an allergic disorder.
- Phase 2: Degree of elevation can be indicative of the diagnosis:
- Most elevations of WBC count are in the 10,000–20,000/mm3 range.
- WBC count in the 30,000/mm3 range is more consistent with pertussis, pneumococcal infection, or acute infectious lymphocytosis.
- Higher counts are worrisome for malignant processes or leukemoid reactions.
- Phase 3: Is the WBC count dangerously elevated?
- WBC of 100,000/mm3 can increase blood viscosity, causing stroke or infarct of end organs.
- Patients with WBC counts this high almost always have a malignant bone marrow process (leukemia, myeloproliferative disorder) and should be referred immediately to a hospital with a pediatric oncologist.
- Children with elevated WBC counts and concurrent anemia and/or thrombocytopenia should also be referred to a pediatric hematologist/oncologist to evaluate for malignancy.
Many laboratories provide only machine-generated differentials. If there are any abnormalities, a manual differential must be obtained. It may be necessary to review the smear with a hematologist or pathologist.
Leukocytosis - history
- Evidence for infection, such as fever, rash, or swelling:
- Infection is the most common cause for leukocytosis.
- Thorough history should be taken for apparent or occult infections.
- Fever can also be a symptom of inflammatory diseases.
- Other complaints:
- Infectious etiologies tend to present acutely.
- If a patient has long-term complaints, broaden the differential or focus it based on specific complaints: Chronic cough may point to tuberculosis, whereas a whooping cough may indicate pertussis.
- Other medical problems:
- Patients with sickle cell disease have an elevated WBC count probably secondary to chronic inflammation or marrow expansion.
- Children with Down syndrome can have a benign leukemoid reaction (especially in the 1st few months of life) that resolves spontaneously.
- Medications:
- Corticosteroids will increase the neutrophil precursors.
- Epinephrine can cause a transitory increase in neutrophil count.
- Familial history of inflammatory diseases: For example, collagen vascular disease such as rheumatoid arthritis, thyroiditis, Crohn disease
- If patient has lost weight, been fatigued, had night sweats, or been pale, malignancy must be ruled out.
Leukocytosis - physical exam
- Foci of infection:
- Look for cellulitis, otitis, pharyngitis, or abscesses on examination.
- A careful lung examination is necessary as pneumonia can cause a WBC count as high as 30,000–40,000/mm3.
- A murmur or gallop may be a sign of bacterial endocarditis.
- UTIs present with dysuria and cloudy urine.
- Lymphadenopathy or hepatosplenomegaly points toward a possible viral etiology but is also of concern for malignancy.
- Tender or swollen joints may indicate juvenile rheumatoid arthritis, septic arthritis, or systemic lupus erythematosus.
- Stigmata of Down syndrome
Leukocytosis - tests
Leukocytosis - lab
- WBC count including differential:
- If neutrophilia is present, think of bacterial infections.
- Pneumonia, urinary tract infections, and soft tissue infections are the most likely to cause leukocytosis.
- May also see Döhle bodies, toxic granulations, or vacuolization in WBCs in bacteremia
- Recovering or stressed marrow may have an increase in monocytes or eosinophils.
- Look for leukemic blasts.
- Hemoglobin/Platelet count: If either is low, consider a marrow-infiltrative process or a marrow that is hyperstimulated and overproducing WBCs as part of a response to a low hemoglobin or platelet count.
- Chemistry panel:
- Evaluate liver function tests for possible viral etiology.
- Uric acid and lactate dehydrogenase are elevated in leukemia and lymphoma.
- Cultures: Blood, urine, stool, throat, and others
- Mono spot, heterophil antibodies, Epstein-Barr virus titers:
- Screen for infectious mononucleosis.
- Mono spot can be falsely negative in younger children.
- Leukocyte alkaline phosphatase:
- Elevated in infection but not in leukemia
- Helps to differentiate chronic myelogenous leukemia from a leukemoid reaction
- Antinuclear antibody: Screen for rheumatologic etiology.
Leukocytosis - imaging
Chest radiograph for pneumonia, tuberculosis
Leukocytosis - diag proced-surgery
Bone marrow biopsy and aspirate:
- Necessary if any other blood cell line is abnormally low or if the WBCs appear dysmorphic
- Need to rule out malignancy, myelodysplasia, or other marrow processes: Send cytogenetics when possible.
Leukocytosis - differencial diagnosis
- Infectious:
- Bacterial:
- Streptococcus (especially pneumoniae)
- Staphylococcus aureus
- Haemophilus
- Neisseria
- Brucella
- Bartonella (cat-scratch disease)
- Clostridium difficile
- Pertussis
- Viral:
- Infectious mononucleosis
- Cytomegalovirus
- Rubella
- Mumps
- Hepatitis
- Fungal: Aspergillus
- Parasitic:
- Toxocara
- Toxoplasma
- Trichinella
- Tapeworms
- Strongyloides
- Coccidioidomycosis
- Tuberculosis
- Syphilis
- Acute infectious lymphocytosis
- Benign viral mediated lymphocytosis (often >25,000/mm3)
- Kawasaki disease
- Congenital/Anatomic:
- Down syndrome
- Sickle cell disease
- Fanconi anemia
- Thrombocytopenia with absent radii
- Leukocyte adhesion deficiency
- Drugs:
- Corticosteroids
- Beta-agonists
- Epinephrine
- Lithium
- Granulocyte colony-stimulating factor
- Granulocyte–macrophage colony-stimulating factor
- Trauma:
- Acute hemorrhage
- Severe burns
- Splenectomy
- Tumor:
- Leukemia
- Lymphoma
- Myeloproliferative disorders
- Genetic/Metabolic:
- Inflammatory:
- Juvenile rheumatoid arthritis
- Rheumatoid arthritis
- Inflammatory bowel disease
- Chronic granulomatous disease
- Pulmonary eosinophilic syndromes: Transient infiltrates associated with a peripheral eosinophilia
- Allergic:
- Asthma
- Seasonal or drug allergies
- Eczema
- Psoriasis
- Hematologic: Severe hemolysis
- Stress:
- Anxiety
- Overexertion/Exercise
- Seizures
- Anesthesia
- Artifactual:
- Nucleated RBCs
- Clumped platelets on a mechanical differential
- Issues for referral:
- WBC counts >50,000/mm3
- Associated thrombocytopenia or anemia
- Any indication of malignancy
- Any indication of a rheumatologic etiology
- Inability to find an etiology with a persistent leukocytosis
Beware of any differential that has a high percentage of monocytes or atypical lymphocytes, whether machine generated or manual. Leukemic blasts can be mistaken for these cell types under the microscope.
Leukocytosis - TREATMENT
- Antibiotics immediately if a child appears septic, otherwise tailor antibiotics to the underlying infectious diagnosis.
- If an underlying rheumatologic, hematologic, or genetic cause is suspected, refer to the appropriate specialist.
- If leukemia is suspected, start hyperhydration with fluids containing bicarbonate and no potassium, and administer oral allopurinol or urate oxidase.
- If the leukocytosis is >100,000/mm3 and the patient has symptoms of end organ failure, emergent leukapheresis should be considered.
- If the patient’s condition is hemodynamically stable, avoid red cell transfusions, which will increase the blood viscosity.
- If the platelet count is <20,000/mm3, transfuse platelets to prevent hemorrhagic complications of hyperviscosity.
Leukocytosis - bibliography
- Abramson N, Melton B. Leukocytosis: Basics of clinical assessment. Am Fam Physician. 2000;62:2053–2060.
- Lowe EJ, Pui CH, Hancock ML, et al. Early complications in children with acute lymphoblastic leukemia presenting with hyperleukocytosis. Pediatr Blood Cancer. 2005;45(1):10–15.
- Peterson L, Hrisinko MA. Benign lymphocytosis and reactive neutrophilia. Clin Lab Med. 1993;13:863–877.
- Shah SS, Shofer FS, Seidel JS, et al. Significance of extreme leukocytosis in the evaluation of febrile children. Pediatr Infect Dis J. 2005;24(7):627–630.
Leukocytosis - CODES
Leukocytosis - icd9
288.60 Leukocytosis, unspecified
Leukocytosis - FAQ
- Q: What does “left-shifted” mean?
- A: Increased numbers of early granulocyte precursors (metamyelocytes, myelocytes, bands) are seen in the peripheral smear with a bandemia and neutrophilia. They are often seen with bacterial infections or marrow recovery from a suppressing drug/virus.
- Q: Infectious mononucleosis and acute lymphocytic leukemia have many similar signs and symptoms. How can I differentiate them?
- A: Both can present with fever, malaise, headache, prominent lymphadenopathy, organomegaly, and suppressed hemoglobin and platelet counts. Infectious mononucleosis tends to be associated with a sore throat, and children with acute lymphocytic leukemia are more likely to complain of bone pain. The easiest way to differentiate the two is a careful exam of the peripheral smear. A heterophil AB or mono spot can be sent and, if positive, help with the diagnosis of infectious mononucleosis.
- Q: What are the signs and symptoms of acute infectious lymphocytosis?
- A: Acute infectious lymphocytosis is probably caused by several viruses from which the child can be totally asymptomatic except for a significant lymphocytosis (40,000–80,000/mm3). On review of the peripheral smear, there is a prevalence of small, mature lymphocytes. There can also be an eosinophilia. As a rule, there is no anemia or thrombocytopenia. The lymphocytosis resolves spontaneously.
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
Other Book Chapters Related to Leukocytosis
Read excerpts from these other book chapters related to Leukocytosis:
Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Williams & Wilkins.
More About Causes of Leukocytosis
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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Medications causing Leukocytosis
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