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==Overview==
==Overview==
* The term '''leukemoid reaction''', also referred to as '''transient myeloproliferative disorder''', describes an elevated [[white blood cell]] count, or [[leukocytosis]], that is a physiologic response to stress or infection (as opposed to a primary blood [[Cancer|malignancy]], such as [[leukemia]]).
Leukemoid reaction is a reversible increase in production of [[white blood cells]] in response to a stimulus, with white blood cell count of more than 25000-30000 per mm<sup>3</sup> [[Leukocytosis]] is increase in white blood cell count of more than 10000 per mm3 and when the count exceeds 25000, with more than 2% immature white blood cells but absence of any [[Blast|blast cells]], differentiating it from [[Leukemia|leukemias]]. Leukemoid reaction is classified according to the type of [[Hematopoiesis|hematopoietic]] lineage of the [[bone marrow]]. Leukemoid reactions are mostly triggered by [[Bacteria|bacterial]] or [[Virus|viral]] infections. Leukemoid reaction is differentiated from leukemias by the absence of [[Blast|blast cells]] on peripheral blood film and high [[Leukocyte alkaline phosphatase|LAP]] score. Leukemoid reaction can lead to serious complications such as [[tumor lysis syndrome]] and [[Disseminated intravascular coagulation|DIC]]. The treatment includes treating the underlying cause and [[leukapheresis]].


==Historical Perspective==
==Historical Perspective==
*[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
*Leukemoid reaction was discovered in 1926 by Krumbharr.
*The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
*In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
*In [year], [gene] mutations were first implicated in the pathogenesis of [disease name]


==Classification==
==Classification==
Leukemoid reaction can be classified according to the course of the disease and the type of hematopoietic lineage of the bone marrow.
Leukemoid reaction can be classified according to the type of [[Hematopoiesis|hematopoietic]] lineage of the bone marrow.
* According to the course of the disease:
# Reactions of [[myeloid]] type
# Phase of expressed manifestations
## [[Neutropenia|Neutrophilic]] leukemoid reactions
# Phase of recession 
## [[Eosinophilic]] leukemoid reactions
# Phase of normalization with trace reactions.
# Reactions of [[Lymphatic system|lymphoid]] type
* According to the type of  hematopoietic lineage of the bone marrow :
## Lymphomonocytic leukemoid reactions
1. Reactions of myeloid type
## [[Lymphocyte|Lymphocytic]] leukemoid reactions
 
## Plasmocytic leukemoid reactions
1.1. Neutrophilicleukemoid reactions  
# Leukemoid reaction with blast cells
 
# Secondary (reactive) [[thrombocytosis]]
1.2. Eosinophilic leukemoid reactions  
# Secondary [[Polycythemia|erythrocytosis]]
 
# Mixed forms of leukemoid reactions
2. Reactions of lymphoid type  
# Rare forms of leukemoid reaction
 
# Leukemoid reactions of [[basophilic]] type.
2.1. Lymphomonocytic leukemoid reactions  
 
2.2. Lymphocytic leukemoid reactions
 
2.3. Plasmocyticleukemoid reactions  
 
2.4. Leukemoid reaction with blast cells  
 
3. Secondary (reactive) thrombocytosis  
 
4. Secondary erythrocytosis  
 
5. Mixed forms of leukemoid reactions  
 
6. Rare forms of leukemoid reaction  
 
6.1. Cytopenia
 
6.2. Leukemoid reactions of basophilic type.


==Pathophysiology==
==Pathophysiology==
* Leukemoid reaction is a reversible increase in production of white blood cells in response to a stimulus.
* Leukemoid reaction is a reversible increase in production of [[white blood cells]] in response to a stimulus, with white blood cell count of more than 25000-30000 per mm<sup>3.</sup>
* Leukemoid reaction is classified acoording to the type of hematopoietic lineage of the bone marrow.
* [[Leukocytosis]] is increase in white blood cell count of more than 10000 per mm3 and when the count exceeds 25000, with more than 2% immature white blood cells but absence of any blasts, differentiating it from [[Leukemia|leukemias]].
* It is a reactive, functional condition of hematopoietic, lymphatic and immune systems secondary to various diseases accompanied by the development of immature white blood cells in the peripheral blood, the number may exceed 50000 per 1 mm3
* Leukemoid reaction is classified according to the type of [[Hematopoiesis|hematopoietic]] lineage of the bone marrow.
* Leukemoid reaction is diagnosed after the exclusion of a malignant hematological disorder.  
* It is a reactive, functional condition of [[Hematopoiesis|hematopoietic]], [[Lymphatic system|lymphatic]] and [[Immunity (medical)|immune]] systems secondary to various diseases accompanied by the development of immature white blood cells in the peripheral blood.
* Leukemoid reaction is diagnosed after the exclusion of a [[malignant]] [[Blood|hematological]] disorder.  
* Changes in blood are transient and blood levels return to normal when the causes disappear.
* Changes in blood are transient and blood levels return to normal when the causes disappear.
* There are no signs of inhibition of normal hematopoiesis.
* There are no signs of inhibition of normal [[hematopoiesis]].
* Leukemoid reactions are mostly triggered by bacterial or viral infections, emergency stress irritants and also by various bacterial and nonbacterial stimulants causing sensitization.
* Leukemoid reactions are mostly triggered by bacterial or viral infections, emergency stress irritants and also by various bacterial and nonbacterial stimulants causing sensitization.
* The sensitization causes upregulation of growth or survival factors (eg, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, c-kit ligand), adhesion molecules (eg, CD11b/CD18), and various cytokines (eg, interleukin-1, interleukin-3, interleukin-6, interleukin-8, tumor necrosis factor).
* The sensitization causes upregulation of growth or survival factors (eg, [[granulocyte colony-stimulating factor]], [[granulocyte-macrophage colony-stimulating factor]], c-kit ligand), [[adhesion]] molecules (eg, [[Integrin alpha M|CD11b]]/CD18), and various [[Cytokine|cytokines]] (eg, [[Interleukin 1|interleukin-1]], [[Interleukin 3|interleukin-3]], [[Interleukin 6|interleukin-6]], [[Interleukin 8|interleukin-8]], [[Tumour necrosis factor|tumor necrosis factor]]).
* There is activation of normal hematopoiesis and excessive blood cells output to peripheral blood (reactive hyperplasia of leukopoietic tissue) and output of immature blood cells into peripheral blood.
* There is activation of normal [[hematopoiesis]] and excessive blood cells output to peripheral blood (reactive [[hyperplasia]] of leukopoietic tissue) and output of immature blood cells into peripheral blood.
* Reactions of myeloid type are characterized by a shift to the left, from an increased number of stab cells to singular blast cells with presence of all intermediate forms.
* Reactions of [[myeloid]] type are characterized by a shift to the left, from an increased number of stab cells to singular blast cells with presence of all intermediate forms.
* There is an increase in immature granulocytes of myeloid lineage.
* There is an increase in immature [[Granulocyte|granulocytes]] of [[myeloid]] lineage.
** Neutrophilic leukemoid reactions develop in Infections (sepsis, scarlet fever, purulent processes, diphtheria, lobar pneumonia, tuberculosis, dysentery, etc), exposure to ionizing radiation, Injuries of the skull, intoxication (uremia, CO poisoning), bone marrow metastases of malignant tumors.
** [[Neutrophilic leukopenia|Neutrophilic]] leukemoid reactions develop in Infections ([[sepsis]], [[scarlet fever]], [[abscess]], [[diphtheria]], [[Pneumonia|lobar pneumonia]], [[tuberculosis]], [[dysentery]], etc), exposure to ionizing [[Radiation therapy|radiation]], Injuries of the skull, intoxication ([[Chronic renal failure pathophysiology|uremia]], [[Carbon monoxide poisoning|CO poisoning]]), bone marrow [[Metastasis|metastases]] of malignant tumors.
** Eosinophilic reactions develop in allergic processes or in diseases with allergies, as well as in parasitic diseases. They are characterized by the development of a great number of eosinophils, about 90% of leukocytes.
** [[Eosinophilic]] reactions develop in [[Allergy|allergic]] processes or in diseases with [[Allergy|allergies]], as well as in [[Parasitism|parasitic]] diseases. They are characterized by the development of a great number of [[eosinophils]], about 90% of leukocytes.
* Lymphomonocytic leukemoid reactions develop in infectious mononucleosis, there are atypical mononuclear cells, called "lymphomonocytes" which are modulated T- and NK-lymphocytes, which get to the bloodstream by initiation of B lymphocytes.The number of atypical mononuclear cells can be increased in any viral infection.
* Lymphomonocytic leukemoid reactions develop in [[Mononucleosis|infectious mononucleosis]], there are atypical mononuclear cells, called "lymphomonocytes" which are modulated [[T cell|T-]] and [[Nk-cell lineage granular lymphocyte proliferative disorder|NK-lymphocytes]], which get to the bloodstream by initiation of [[B cell|B lymphocytes]].The number of atypical mononuclear cells can be increased in any [[Virus|viral]] infection.
* Lymphocytic leukemoid reactions develop in acute viral and bacterial infections and are characterized by leukocytosis with absolute lymphocytosis.
* Lymphocytic leukemoid reactions develop in acute viral and bacterial infections and are characterized by [[leukocytosis]] with absolute [[lymphocytosis]].
* Plasmocytic leukemoid reactions occur in diseases caused by protozoa (toxoplasmosis), viral infections (chickenpox, measles, rubella). Increased level of plasma cells (2%) in splenomegaly, blood and bone marrow.
* Plasmocytic leukemoid reactions occur in diseases caused by [[protozoa]] ([[toxoplasmosis]]), [[Virus|viral infections]] ([[chickenpox]], [[measles]], [[rubella]]). Increased level of plasma cells (2%) in [[splenomegaly]], [[blood]] and [[bone marrow]].
* Leukemoid reactions with blast cells develop in severe viral infections (cytomegalovirus, etc.). Blast transformation of B-lymphocytes may be observed in the bone marrow, lymph nodes and peripheral blood.
* Leukemoid reactions with blast cells develop in severe viral infections ([[cytomegalovirus]], etc.). Blast transformation of [[B cell|B-lymphocytes]] may be observed in the bone marrow, lymph nodes and peripheral blood.
* Secondary absolute erythrocytosis is caused by increased erythropoiesis, relative hemoconcentration and polycythemia. It is characterized by increased red blood cell count.
* Secondary absolute [[Polycythemia|erythrocytosis]] is caused by increased [[erythropoiesis]], relative hemoconcentration and [[polycythemia]]. It is characterized by increased red blood cell count.
* Secondary thrombocytosis is possible in malignant tumors, inflammatory diseases, following bleeding, hemolytic crises, after surgical operations and splenectomy.
* Secondary [[thrombocytosis]] is possible in [[malignant]] tumors, [[Inflammation|inflammatory diseases]], following [[bleeding]], [[Hemolysis|hemolytic]] crises, after surgical operations and [[splenectomy]].


==Causes==
==Causes==
* Neutrophilic leukemoid reactions :
* Neutrophilic leukemoid reactions :
** Infections - sepsis, scarlet fever, purulent processes, diphtheria, lobar pneumonia, tuberculosis and dysentery.
** Infections - [[sepsis]], [[scarlet fever]], [[abscess]], [[diphtheria]], [[Pneumonia|lobar pneumonia]], [[tuberculosis]], [[dysentery]]
** Exposure to ionizing radiation.
** Exposure to ionizing [[Radiation therapy|radiation]].
** Injuries of the skull.
** Injuries of the skull.
** Intoxication (uremia, CO poisoning).
** Intoxication ([[Chronic renal failure pathophysiology|uremia]], CO poisoning).
** Bone marrow metastases of malignant tumors - Lymphogranulomatosis
** Bone marrow metastases of malignant tumors - [[Lymphogranulomatosis X T-cell lymphoma|Lymphogranulomatosis]]
** Steroid hormones therapy
** [[Steroid]] hormones therapy
* Eosinophilic reactions :
* Eosinophilic reactions :
** Allergic processes or in diseases with allergies, as well as in parasitic diseases.  
** Allergic processes or in diseases with [[Allergy|allergies]], as well as in [[Parasitism|parasitic]] diseases.  
* Lymphomonocytic leukemoid reactions:  
* Lymphomonocytic leukemoid reactions:  
** Infectious mononucleosis.
** [[Mononucleosis|Infectious mononucleosis]].
* Lymphocytic leukemoid reaction:
* Lymphocytic leukemoid reaction:
** Acute viral and bacterial infections
** Acute [[Virus|viral]] and [[Bacteria|bacterial]] infections
* Plasmocytic leukemoid reactions:
* Plasmocytic leukemoid reactions:
** Diseases caused by protozoa (toxoplasmosis), and viral infections (chickenpox, measles, rubella).
** Diseases caused by [[protozoa]] ([[toxoplasmosis]]), and viral infections ([[chickenpox]], [[measles]], [[rubella]]).
* Thrombocytosis:
* [[Thrombocytosis]]:
** Primary thrombocytosis- chronic myeloproliferative diseases.
** Primary thrombocytosis- chronic [[Myeloproliferative neoplasm|myeloproliferative]] diseases.
** Secondary thrombocytosis-
** Secondary [[thrombocytosis]]-
*** Malignant tumors
*** Malignant tumors
*** Inflammatory diseases
*** Inflammatory diseases
Line 96: Line 75:
* Leukemoid reactions of basophilic type:
* Leukemoid reactions of basophilic type:
** [[Allergy|Allergic]] reactions
** [[Allergy|Allergic]] reactions
** Hemolytic anemia
** [[Hemolytic anemia]]
** Ulcerative colitis
** [[Ulcerative colitis]]
** Hypothyroidism
** [[Hypothyroidism]]
** Leukemia.
** [[Leukemia]].


==Differentiating Leukemoid reaction from Other Diseases==
==Differentiating Leukemoid reaction from Other Diseases==
Line 155: Line 134:


==Epidemiology and Demographics==
==Epidemiology and Demographics==
=== Age ===
* Patients of all age groups may develop leukemoid reaction.
* Normal white blood count differential changes with age.
* Leukemoid reaction in neonates is more common, compared to children and adults.
=== Gender ===
* Leukemoid reaction affects men and women equally.
=== Race ===
* There is no racial predilection for the development of leukemoid reaction.


==Risk Factors==
==Risk Factors==
 
*Common risk factors in the development of leukocytosis, include:<ref name="pmid11087187">{{cite journal |vauthors=Abramson N, Melton B |title=Leukocytosis: basics of clinical assessment |journal=Am Fam Physician |volume=62 |issue=9 |pages=2053–60 |year=2000 |pmid=11087187 |doi= |url=}}</ref>
**Physiologic processes (eg, stress, exercise, [[pregnancy]])
**Drugs (e.g.[[Corticosteroid|corticosteroids]])
**Trauma
==Screening==
==Screening==
No screening is done for leukemoid reaction.


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
===Natural History===


=== History ===
*The majority of patients with leukemoid reaction are initially symptomatic.<ref name="wiki" />
*Early clinical features, include:<ref name="wiki">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016</ref>
**[[Fever]]
**[[Hyperhidrosis]]
**[[Fatigue]]
===Complications===
===Complications===
*Common complications of leukemoid reaction, include:<ref name="wiki" />
**[[Tumor lysis syndrome]]
**[[Disseminated intravascular coagulation|Disseminated intravascular coagulopathy]]
**[[Acute respiratory failure]]
**[[Pulmonary hemorrhage]]
**[[CNS infarction]]
**Splenic infarction
**[[Myocardial ischemia]]
**[[Renal failure]]


===Prognosis===
=== Prognosis ===
 
*Prognosis generally depends on the underlying etiologies.
*If the white blood cell count reaches more than 50000 per mm3, life threatening complications can ocuur.
==Diagnosis==
==Diagnosis==
===Diagnostic Criteria===
===Symptoms===
 
*Leukemoid reaction is usually symptomatic.
===History and Symptoms===
*Symptoms of leukemoid reaction are often unspecific, such as:<ref name="wiki2">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016</ref>
 
**[[Weight loss]]
===Physical Examination===
**[[Fevers of unknown origin]]
 
**[[Hyperhidrosis]]
===Laboratory Findings===
**Chronic pain
Conventionally, a leukocytosis exceeding 50,000 WBC/mm<sup>3</sup> with a significant increase in early [[neutrophil]] precursors is referred to as a leukemoid reaction.<ref>{{cite book | author = Ronald Hoffman et al. | title = Hematology: basic principles and practice | publisher = Elsevier Churchill Livingstone | location = St. Louis, Mo | year = 2005 | id = ISBN 0-443-06628-0}} p. 803.</ref> The peripheral blood smear may show [[myelocyte]]s, [[metamyelocyte]]s, [[promyelocyte]]s, and even [[myeloblasts]]; however, there is a mix of early mature neutrophil precursors, in contrast to the immature forms typically seen in [[acute leukemia]]. The [[bone marrow]] in a leukemoid reaction, if [[bone marrow biopsy|examined]], may be hypercellular but is otherwise typically unremarkable.
**[[Fatigue]]
 
**[[Dyspnea]]
Leukemoid reactions are generally benign and are not dangerous in and of themselves, although they are often a response to a significant disease state (see ''Causes'' below). However, leukemoid reactions can resemble more serious conditions such as [[chronic myelogenous leukemia]] (CML), which can present with identical findings on peripheral blood smear.
**[[Malaise]]


Historically, various clues including the [[leukocyte alkaline phosphatase]] score and the presence of [[basophilia]] were used to distinguish CML from a leukemoid reaction. However, at present the test of choice in adults to distinguish CML is an assay for the presence of the [[Philadelphia chromosome]], either via [[cytogenetics]] and [[Fluorescent in situ hybridization|FISH]], or via [[PCR]] for the Bcr/abl fusion protein. The LAP (Leukocyte Alkaline Phosphatase) score is high in reactive states but is low in CML.  In cases where the diagnosis is uncertain, a qualified [[hematologist]] or [[oncologist]] should be consulted.
*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 leukemoid reaction, include:<ref name="wiki3">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016</ref>
**White blood cell count above the normal range, greater than 25000 per mm<sup>3</sup>.
**Bone marrow aspiration reveals hyperplasia of normal [[Hematopoiesis|hematopoietic]] cells in proliferative reactions. The presence of blast and immature forms of [[leukocyte]], [[platelet]] and erythrocyte hematopoiesis in the proliferative reactions.
**The peripheral blood smear shows [[myelocyte]]s, [[metamyelocyte]]s, [[promyelocyte]]s, and small amount of [[myeloblasts|myeloblasts.]]
**[[leukocyte alkaline phosphatase]] score is more than 100.
===Electrocardiogram===
===Electrocardiogram===
No specific ECG changes in leukemoid reaction.


===X-Ray===
===X-Ray===
No specific x ray changes in leukemoid reaction.


===Echocardiograph and Ultrasound===
===Echocardiograph and Ultrasound===
No echocardiography and ultrasound findings.


===CT===
===CT===
No CT scan findings in leukemoid reaction.


===MRI===
===MRI===
 
No specific MRI findings in leukemoid reaction.
===Imaging Findings===
 
===Other Diagnostic Studies===


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
* The treatment of leukemoid reaction depends on the underlying cause.
* Measures to reduce white blood cell count include:
** [[Leukapheresis]] or exchange blood transfusion.
** [[Hydration]]
** Urine alkalinization
** Administration of [[allopurinol]] or [[rasburicase]] to reduce serum [[uric acid]] and minimize [[tumor lysis syndrome]].


===Surgery===
=== Surgery ===
The treatment depends on the underlying cause.


===Primary Prevention===
=== Primary prevention ===
Prevention and treatment of [[Infection|infections]].


===Secondary Prevention===
=== Secondary prevention ===
Treatment of underlying cause and reduction of [[white blood cell count]].


==See also==
==See also==

Revision as of 19:24, 9 October 2018

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Overview

Leukemoid reaction is a reversible increase in production of white blood cells in response to a stimulus, with white blood cell count of more than 25000-30000 per mm3 Leukocytosis is increase in white blood cell count of more than 10000 per mm3 and when the count exceeds 25000, with more than 2% immature white blood cells but absence of any blast cells, differentiating it from leukemias. Leukemoid reaction is classified according to the type of hematopoietic lineage of the bone marrow. Leukemoid reactions are mostly triggered by bacterial or viral infections. Leukemoid reaction is differentiated from leukemias by the absence of blast cells on peripheral blood film and high LAP score. Leukemoid reaction can lead to serious complications such as tumor lysis syndrome and DIC. The treatment includes treating the underlying cause and leukapheresis.

Historical Perspective

  • Leukemoid reaction was discovered in 1926 by Krumbharr.

Classification

Leukemoid reaction can be classified according to the type of hematopoietic lineage of the bone marrow.

  1. Reactions of myeloid type
    1. Neutrophilic leukemoid reactions
    2. Eosinophilic leukemoid reactions
  2. Reactions of lymphoid type
    1. Lymphomonocytic leukemoid reactions
    2. Lymphocytic leukemoid reactions
    3. Plasmocytic leukemoid reactions
  3. Leukemoid reaction with blast cells
  4. Secondary (reactive) thrombocytosis
  5. Secondary erythrocytosis
  6. Mixed forms of leukemoid reactions
  7. Rare forms of leukemoid reaction
  8. Leukemoid reactions of basophilic type.

Pathophysiology

Causes

Differentiating Leukemoid reaction from Other Diseases

Leukemoid reaction is differentiated from leukemia by following ways:

Leukemia vs leukemoid reaction
Differentiating features Leukemia Leukemoid reaction
Causes Carcinogens Infectious agents, biologically active substances and

products of tissue destruction

Pathogenesis The transformation of normal haematopoietic

cells to a tumor

Activation of normal hematopoiesis and exit of immature leukocytes

into the bloodstream.

Duration Chronic Temporary and reversible
Genetic level Defect No defect
Splenomegaly Present Not present
Peripheral blood Immature cells, pancytopenia Mature and immature granulocytes with left shift
Bone marrow Increase in blasts and immature cells Myeloid hyperplasia and normal morphology
LAP score Low High
Toxic granules 
(suggestive of infection)
Absent Present
Dohle inclusion bodies Absent Present

Epidemiology and Demographics

Age

  • Patients of all age groups may develop leukemoid reaction.
  • Normal white blood count differential changes with age.
  • Leukemoid reaction in neonates is more common, compared to children and adults.

Gender

  • Leukemoid reaction affects men and women equally.

Race

  • There is no racial predilection for the development of leukemoid reaction.

Risk Factors

  • Common risk factors in the development of leukocytosis, include:[1]

Screening

No screening is done for leukemoid reaction.

Natural History, Complications, and Prognosis

History

Complications

Prognosis

  • Prognosis generally depends on the underlying etiologies.
  • If the white blood cell count reaches more than 50000 per mm3, life threatening complications can ocuur.

Diagnosis

Symptoms

  • Obtain history of the following:
    • Clinical features
    • Duration (e.g. days, weeks, months)
    • Remainder of complete blood count

Laboratory findings

Electrocardiogram

No specific ECG changes in leukemoid reaction.

X-Ray

No specific x ray changes in leukemoid reaction.

Echocardiograph and Ultrasound

No echocardiography and ultrasound findings.

CT

No CT scan findings in leukemoid reaction.

MRI

No specific MRI findings in leukemoid reaction.

Treatment

Medical Therapy

Surgery

The treatment depends on the underlying cause.

Primary prevention

Prevention and treatment of infections.

Secondary prevention

Treatment of underlying cause and reduction of white blood cell count.

See also

References

  1. ↑ Abramson N, Melton B (2000). "Leukocytosis: basics of clinical assessment". Am Fam Physician. 62 (9): 2053–60. PMID 11087187.
  2. ↑ 2.0 2.1 2.2 Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016
  3. ↑ Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016
  4. ↑ Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016


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