Leukocytosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2] Lakshmi Gopalakrishnan, M.B.B.S. [3]

Synonyms and Keywords: Elevated white blood cell count; Right-shift leukocytosis; Left-leukocytosis

Overview

Leukocytosis is an elevation of the white blood cell count above the normal range (greater than 11,000 per mm3). Leukocytosis is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasitic infections, bone tumors, strenuous exercise, emotional stress, pregnancy, anesthesia, and epinephrine administration. Leukocytosis may be classified into 5 subtypes: neutrophilia (most common), lymphocytosis, monocytosis, eosinophilia, and basophilia. Other classification, include: Left shift or right shift leucocytosis. The pathogenesis of leukocytosis is characterized by the increase of leukocytes (primarily neutrophils), followed by the proliferation and release of granulocyte and monocyte precursors in the bone marrow which is stimulated by several products of inflammation including C3a and G-CSF.[1]

Historical Perspective

  • Leukocytosis was first discovered by Paul Kautchakoff, in 1846.[1]

Classification

  • Leukocytosis may be classified into 5 subtypes:[2]
  • Leukocytosis may also be classified into 2 groups:[2]
  • Left shift (most common)
  • Immature leukocytes increase
  • Proliferation and release of granulocyte and monocyte precursors in the bone marrow
  • Usually stimulated by several products of inflammation including C3a and G-CSF
  • Right shift
  • Another variant of leukocytosis is the leukemoid reaction.
  • The image below demonstrates a graphic figure that illustrates hematopoietic growth factors in leukocytosis.[3]
Hematopoietic growth factors in leukocytosis, Courtesy of Wikipedia

Pathophysiology

  • The pathogenesis of leukocytosis is characterized by:[2]
  • An increased release of leukocytes from bone marrow storage pools
  • Decreased margination of leukocytes onto vessel walls
  • Decreased extravasation of leukocytes from the vessels into tissues
  • Increase in number of precursor cells in the bone marrow

Causes

  • To see a comprehensive list of all causes of leukocytosis, please click here
Causes of leukocytosis
Neutrophilic
leukocytosis
(neutrophilia)
Eosinophilic
leukocytosis
(eosinophilia)
Basophilic
leukocytosis
Basophilia
Monocytosis
Lymphocytosis

Epidemiology and Demographics

  • Leukocytosis is very common.[2]

Age

  • Patients of all age groups may develop leukocytosis.
  • Normal white blood count differential changes with age.
  • Leukocytosis in neonates is more common, compared to children and adults.[2]

Gender

  • Leukocytosis affects men and women equally.

Race

  • There is no racial predilection for leukocytosis.

Risk Factors

  • Common risk factors in the development of leukocytosis, include:[2]

Natural History, Complications and Prognosis

  • The majority of patients with leukocytosis are initially symptomatic.[3]
  • Early clinical features, include:[3]
  • Common complications of leukocytosis, include:[3]
  • Prognosis is generally depends on the underlying etiologies.[3]

Diagnosis

Symptoms

  • Leukocytosis is usually symptomatic.
  • Symptoms of leukocytosis are often unspecific, such as:[3]
  • Obtain history of the following:
  • Clinical features
  • Duration (e.g. days, weeks, months)
  • Remainder of complete blood count

Laboratory Findings

  • Laboratory findings consistent with the diagnosis of leukocytosis, include:[3]
  • Greater than 11,000 per mm3

Differentiating Leukocytosis from Other Diseases

Category Condition Etiology Mechanism Congenital Acquried Clinical manifestations Para−clinical findings Gold standard Associated findings
Demography History Symptoms Signs
Lab Findings
Physiologic Increased bone marrow production Demargination of peripheral blood neutrophils Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other CBC PBS Bone marrow exam ESR/CRP BUN/Cr LFT
Autonomous Reactive WBC HB Plt
Hematologic Hereditary neutrophilia[4] + + Rare autosomal dominant genetic disorder
  • Positive family history
Normal Nl + Nl Nl Nl Nl Nl Nl Molecular testing
Myeloproliferative neoplasms[5] + + + Elderly Exposure to ± + Nl + ↑/↓ ↑/↓ Nl Nl Bone marrow examination + clinical manifestation
Polycythemia vera[6] + + Mean age >60 years old + + Nl to ↑
  • Elevated normochromic, normocytic RBCs
  • Thrombocytosis
  • ≥ 10% immature myeloid precursors
  • Leukoerythroblastic picture
Nl Nl Nl Bone marrow examination + clinical manifestation
Microangiopathic hemolytic anemia (MAHA)[7] + + + Any + + + NA Bone marrow examination + clinical manifestation
Leukoerythroblastosis[8] + + Any + Nl + Nl Bone marrow biopsy
Immunology/

Rheumatology

Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings
Leukocyte adhesion deficiency[9] + + Rare autosomal recessive, LAD II more in Middle East and Brazil
  • Positive family history
+ Nl ↓/↑
  • Leukocytosis
  • Leukocytosis
Nl Nl Nl Flow cytometry
Cryopyrin-associated periodic syndromes[10] + + Autosomal dominant autoinflammatory syndrome
  • Positive family history
+ Nl + ↓/↑
  • Leukocytosis
  • Leukocytosis
Nl Genetic tests
Rheumatoid arthritis[11][12] + + Any, more in young women, between 30-60 years old + Nl +
  • Leukocytosis
NA Nl Nl Clinical manifestation + positive anti-CCP antibodies
Juvenile onset rheumatoid arthritis[13] + + Children under the age of 16
  • Positive family history
  • Blotchy rash on a child's arms and legs
+ Nl + +
  • Leukocytosis
NA Nl Nl Clinical manifestation + laboratory findings
Adult Still's disease[14] + + Rare autoimmune disease NA + Nl + +
  • Leukocytosis
NA Nl Nl Diagnosis of exclusion
Kawasaki disease[15] + + Autoimmune disease, more in Asian ethnicity boys NA + + Nl + +
  • Leukocytosis
NA Nl Nl Diagnostic criteria
IBD[16] + + Autoimmune disease, more in young
  • Stress
  • Positive family history
+ + Nl + + +
  • Leukocytosis
NA Nl Nl Colonoscopy and biopsy
Sarcoidosis[17] + + Autoimmune disease, more in young African American women
  • Positive family history
+ + Nl + +

Bilateral hilar adenopathy

+
  • Leukocytosis
NA Nl Nl Diagnosis of exclusion
Chronic hepatitis[18] + + Elderly + + + + +
  • Leukocytosis
NA Liver biopsy
Sweet syndrome[19] + + Rare + + Nl + +
  • Leukocytosis
Nl Nl Diagnostic criteria
Acute gout[20] + + Older males + +
  • Leukocytosis
NA Nl Clinical manifestation
Medication Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings
Steroid[21] + + + Any + Nl to ↓ Nl to ↓ Nl Clinical manifestation + history of drug consumption
Filgrastim (Myeloid growth factor)[22] + + + Any + Nl to ↓ + Nl to ↓ NA NA Nl Nl Clinical manifestation + history of drug consumption
Lithium[23]
  • Unknown
+ + + Any Nl Nl to ↓ NA NA Nl Nl Clinical manifestation + history of drug consumption
Catecholamines

(epinephrine)[24]

  • Stimulation of bone marrow myelopoiesis
  • Egress into the circulation
+ + + Any Nl to ↓ Nl Nl Clinical manifestation + history of drug consumption
ATRA[25] + + + Any Nl Nl Nl NA NA Nl Clinical manifestation + history of drug consumption
Other Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings
Infections[26] + + + + Any
  • Acutely ill
+ + Nl to ↓ ± ± ± Nl Nl Clinical manifestation+ culture
  • Depends on etiology
Allergy[27]
  • Unknown
  • Activation of chloride transport
+ + + + Any Nl to ↓ Nl Nl Clinical manifestation
Post splenectomy[28]
  • Unknown
+ + + Any
  • Normal
± Nl + Nl Nl Clinical manifestation
Cigarette smoking[29] + + + Any Nl NA NA Nl Nl Nl Clinical manifestation
Stress/exercise[30]
  • Reduced plasma volume
+ + + Athlete
  • Normal
Nl Nl Nl Clinical manifestation
Infancy[31] Physiologic + + Infancy
  • Normal
Nl NA NA Nl Nl Nl Clinical manifestation
Pregnancy[32] Physiologic + + Pregnancy
  • Normal
Nl NA NA Nl Nl Nl Clinical manifestation
Platelet clumping[33] Spurious + Any
  • Normal
Nl Nl Nl Nl Nl Nl Clinical manifestation
Mixed cryoglobulinemia[34] Spurious + Any Nl + Nl to ↓ Nl Nl Nl Nl Skin biopsy
Category Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings

References

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  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016
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