Basics
Description
Definition:
- Any elevation of total number of white blood cells (WBCs) beyond expected value
- Normal range for total WBCs (/mm3):
- Adults: 4,500 " 11,000
- Children: WBC count decreases with age:
- Infant, 1 wk old: 5,000 " 21,000
- Toddler, 1 yr old: 6,000 " 17,500
- Child, 4 yr old: 5,500 " 15,500
- Pregnancy:
- 1st trimester: 5,000 " 14,000
- 2nd trimester: 5,000 " 15,000
- 3rd trimester: 5,000 " 17,000
- Normal ranges shift upward with:
- Exercise
- Female gender
- Smoking
- Daytime hours
- Given wide range of normal values, numbers must be interpreted in clinical context
- Specific subsets
- Neutrophil predominance (neutrophilia):
- Absolute neutrophil count >7,500/mm3
- Half of circulating neutrophils are adherent to blood vessel walls. They can be rapidly released (demarginate) in response to acute stressors. This can double the WBC count.
- An additional pool of mature neutrophils, immature metamyelocytes, and band neutrophils are stored in the bone marrow. These can be released increasing the neutrophil count typically during inflammation or infection. Release of immature forms results in a "left shift. "
- Lymphocyte predominance (lymphocytosis)
- Absolute lymphocyte count >4,000/mm3
- Stored in the spleen, lymph nodes, thymus, and bone marrow. They are typically released in response to foreign antigens or viral infections
- Hyperleukocytosis (WBC >100,000/mm3):
- Seen primarily in hematologic malignancies
- Associated with leukostasis which can lead to cerebral infarction, pulmonary insufficiency, death
Epidemiology
- CBC most common test ordered from the emergency department
- Leukocytosis is one of the most commonly found lab abnormalities.
- Elevated WBC count can be found in 17% of ED patients in whom a CBC is checked (Callaham)
Etiology
- Neutrophil predominance:
- Demargination/stress reaction:
- Stress
- Exercise
- Surgery
- Seizures
- Trauma
- Hypoxia
- Pain
- Vomiting
- Inflammation:
- Rheumatoid arthritis
- Gout
- Inflammatory bowel disease
- Infection, generally bacterial
- Lab error
- Labor
- Leukemoid reaction (TB, Hodgkin, sepsis, metastatic CA)
- Medications:
- ²-Agonist (epinephrine, cocaine, parenteral albuterol)
- Corticosteroids
- Lithium
- Granulocyte colony stimulating factor
- Metabolic disorders:
- Malignancy, nonhematogenous
- Myeloproliferative disorders:
- Chronic myeloid leukemia
- Polycythemia vera
- Pregnancy
- Rapid RBC turnover:
- Tissue necrosis:
- Lymphocyte predominance:
- Infection, generally viral, early stages:
- Mononucleosis
- VZV
- CMV
- Viral hepatitis
- Bacterial infection, specifically:
- Pertussis
- TB
- Syphilis
- Rickettsia
- Babesia
- Bartonella
- Hypothyroidism
- Immunologic responses:
- Immunization
- Autoimmune diseases
- Graft rejection
- Lymphoproliferative disease:
- Acute lymphocytic leukemia
- Chronic lymphocytic leukemia
- Non-Hodgkin lymphoma
- Splenectomy
Diagnosis
Signs and Symptoms
History
- Depends upon presenting complaint
- Symptoms suggestive of infection:
- Cough
- Fever
- Rash
- GI symptoms
- Symptoms suggestive of long-term inflammation:
- Symptoms suggestive of malignancy:
- Weight loss
- Fatigue
- Night sweats
Physical Exam
- Focal signs of infection:
- Cellulitis/abscess
- Otitis
- Pharyngitis
- Pneumonia
- Signs of malignancy:
- Hepatosplenomegaly
- Lymphadenopathy
- Pallor
- Bleeding
- Signs of chronic inflammatory conditions:
- Joint pain and swelling
- Rash
Diagnosis Tests & Interpretation
- Interpretation of leukocytosis:
- Elevated WBC counts are highly nonspecific and rarely change management. They have equal chances of appropriately and inappropriately influencing care
- Duration of leukocytosis:
- Hours to days: More likely to be acute event (infection, acute leukemia)
- Months to years: Chronic inflammatory states or hematologic malignancies (rheumatoid arthritis, solid organ tumors, chromic leukemias, lymphomas)
- Cell count and differential:
- If obtained be sure to evaluate absolute cell counts, percentile counts will be spuriously elevated if other cell lines are low
- Look for the presence of a "left shift " (immature cells in circulation). Normal ratio is 1 band cell for every 10 neutrophils in circulation. This may indicate acute infection, or malignancy. Demargination should not cause a left shift.
- Differential rarely provides additional helpful information and cannot reliably distinguish between bacterial and viral infections.
- Manual differential or peripheral blood smear:
- Can be ordered if concern for lab error. Nucleated RBCs, or clumped platelets may cause spurious results in automated tests.
- RBC and platelet counts:
- Low counts may suggest malignancy or bone marrow infiltration
- Pediatrics:
- Evaluation of young febrile children (<36 mo):
- WBC >15,000 is associated with a high risk of serious bacterial infection and in the appropriate clinical context should prompt clinicians to consider antibiotics, blood cultures, and possible admission.
- Providers should not be reassured by only moderately elevated WBC counts 15 " 25,000
- Conversely, the presence of a significantly elevated WBC count >25,000 does not signify more significant illness
- Crying shown to elevate WBC count 113%
Essential Workup
- Dependent upon clinical scenario
- Cell count differential with absolute cell counts may be helpful if the etiology is not apparent based on history and physical exam alone, or if hematologic malignancy is considered
- If hematologic malignancy is suspected patients will require peripheral blood smear and bone marrow biopsy following admission
Differential Diagnosis
See etiology. Narrow diagnosis based on corresponding clinical presentation.
Treatment
- Based on underlying disease process.
- Leukostasis secondary to the extremely high WBC counts of malignancy may require acute management with:
- IV hydration
- Transfusion
- Allopurinol
- Hydroxyurea
- Hematology consult for leukapheresis
Follow-Up
Disposition
Dependent upon clinical scenario. Avoid making disposition decisions based solely on the WBC count.
Pearls and Pitfalls
- Be aware that the decision making of health care providers is significantly influenced by the presence of a leukocytosis
- Increased admission rate
- Increased number of tests and cost
- Wide variety of conditions can cause a leukocytosis, including normal variants
- Poor sensitivity and specificity for predicting severity of illness
- Extremely high WBC counts typically in the setting of hematologic malignancy can be associated with leukostasis which can be life threatening and require emergent therapy
Additional Reading
- Callaham M. Inaccuracy and expense of the leukocyte count in making urgent clinical decisions. Ann Emerg Med. 1986;15(7):774 " 781.
- Cerny J, Rosmarin AG. Why does my patient have leukocytosis? Hematol Oncol Clin North Am. 2012;26:303 " 319.
- Janz TG, Hamilton GC. Anemia, polycythemia, and white blood cells disorders. In: Marx JA, Hockberger RS, Walls RM, et al., eds. Rosens Emergency Medicine: Concepts and Clinical Practice. 7th ed. Philadelphia, PA: Mosby Elsevier; 2009.
- Shah SS. Clinical significance of extreme leukocytosis in the emergency department evaluation of young febrile children. Acad Emerg Med. 2003;10(5):443 " 444.
Codes
ICD9
- 288.8 Other specified disease of white blood cells
- 288.60 Leukocytosis, unspecified
- 288.61 Lymphocytosis (symptomatic)
ICD10
- D72.820 Lymphocytosis (symptomatic)
- D72.828 Other elevated white blood cell count
- D72.829 Elevated white blood cell count, unspecified
SNOMED
- 111583006 Leukocytosis (disorder)
- 414850009 neutrophilia (disorder)
- 67023009 Lymphocytosis (disorder)