Leukemoid reaction: Difference between revisions

Jump to navigation Jump to search
 
(17 intermediate revisions by 3 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{SI}}
{{SI}}
{{CMG}}
{{CMG}} {{shyam}} {{AE}} {{JSS}}
 
{{PleaseHelp}}


==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 25,000-30,000 per mm<sup>3</sup> . [[Leukocytosis]] is increase in white blood cell count of more than 10,000 per mm<sup>3</sup> and when the count exceeds 25,000 per mm<sup>3</sup>, 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 [[Leukemia|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]]<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>.
* 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
* Leukemoid reaction with blast cells
* Secondary (reactive) [[thrombocytosis]]
* Secondary [[Polycythemia|erythrocytosis]]
* Mixed forms of leukemoid reactions
* Rare forms of leukemoid reaction
* Leukemoid reactions of [[basophilic]] type.


1.1. Neutrophilicleukemoid reactions
==Pathophysiology==
 
* 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><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>.
1.2. Eosinophilic leukemoid reactions
* [[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|blasts]], differentiating it from [[Leukemia|leukemias.]]<ref name="pmid5558646">{{cite journal| author=Ward HN, Reinhard EH| title=Chronic idiopathic leukocytosis. | journal=Ann Intern Med | year= 1971 | volume= 75 | issue= 2 | pages= 193-8 | pmid=5558646 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5558646  }} </ref>
 
* Leukemoid reaction is classified according to the type of [[Hematopoiesis|hematopoietic]] lineage of the bone marrow.
2. Reactions of lymphoid type
* 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 and is a transient condition. [[white blood cells]] return to normal when the underlying causes disappear.
2.1. Lymphomonocytic leukemoid reactions
* There are no signs of inhibition of normal [[hematopoiesis]].
 
* Leukemoid reactions are mostly triggered by bacterial or viral [[Infection|infections]], emergency stress irritants, and by various bacterial and non-bacterial stimulants causing '''sensitization'''.
2.2. Lymphocytic leukemoid reactions
* The sensitization causes up-regulation 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.
2.3. Plasmocyticleukemoid reactions
* The image below demonstrates a graphic figure that illustrates hematopoietic growth factors in [[leukocytosis]].<ref name="wiki">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016 </ref>
 
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
[[Image:Hematopoietic growth factors.png|600px|center|thumb|Hematopoietic growth factors in leukocytosis, By Hematopoietic_growth_factors.svg: Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007) Rang & Dale's pharmacology, Churchill Livingstone ISBN: 0-443-06911-5.User:Mikael Häggström and A. Radderivative work: Furfur - This file was derived from: Hematopoietic growth factors.svg:, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=31083166]]


6.2. Leukemoid reactions of basophilic type.


==Pathophysiology==
* 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.
* Leukemoid reaction is a reversible increase in production of white blood cells in response to a stimulus.
* There is an increase in immature [[Granulocyte|granulocytes]] of [[myeloid]] lineage.
* Leukemoid reaction is classified acoording to the type of hematopoietic lineage of the bone marrow.
** [[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<ref name="pmid12032893">{{cite journal| author=Wanahita A, Goldsmith EA, Musher DM| title=Conditions associated with leukocytosis in a tertiary care hospital, with particular attention to the role of infection caused by clostridium difficile. | journal=Clin Infect Dis | year= 2002 | volume= 34 | issue= 12 | pages= 1585-92 | pmid=12032893 | doi=10.1086/340536 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12032893  }} </ref><ref name="pmid17314214">{{cite journal| author=Lawrence YR, Raveh D, Rudensky B, Munter G| title=Extreme leukocytosis in the emergency department. | journal=QJM | year= 2007 | volume= 100 | issue= 4 | pages= 217-23 | pmid=17314214 | doi=10.1093/qjmed/hcm006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17314214  }} </ref>.
* 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
** [[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.
* Leukemoid reaction is diagnosed after the exclusion of a malignant hematological disorder.
* 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<ref name="pmid5635603">{{cite journal| author=McBride JA, Dacie JV, Shapley R| title=The effect of splenectomy on the leucocyte count. | journal=Br J Haematol | year= 1968 | volume= 14 | issue= 2 | pages= 225-31 | pmid=5635603 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5635603  }} </ref>.
* Changes in blood are transient and blood levels return to normal when the causes disappear.
* Lymphocytic leukemoid reactions develop in acute viral and bacterial infections and are characterized by [[leukocytosis]] with absolute [[lymphocytosis]].
* There are no signs of inhibition of normal hematopoiesis.
* 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 are mostly triggered by bacterial or viral infections, emergency stress irritants and also by various bacterial and nonbacterial stimulants causing sensitization.
* 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 node|lymph nodes]], and peripheral blood.
* 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).
* Secondary absolute [[Polycythemia|erythrocytosis]] is caused by increased [[erythropoiesis]], relative hemoconcentration and [[polycythemia]]. It is characterized by increased [[red blood cell]] count.
* 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.
* Secondary [[thrombocytosis]] is possible in [[malignant]] tumors, [[Inflammation|inflammatory diseases]], following [[bleeding]], [[Hemolysis|hemolytic]] crises, after surgical operations and [[splenectomy]].
* 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.
** 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.
** 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.
* 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.
* 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.
* 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.
* Secondary absolute 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.


==Causes==
==Causes==
* Neutrophilic leukemoid reactions :
* Neutrophilic leukemoid reactions <ref name="pmid5058244">{{cite journal| author=Spencer RP, McPhedran P, Finch SC, Morgan WS| title=Persistent neutrophilic leukocytosis associated with idiopathic functional asplenia. | journal=J Nucl Med | year= 1972 | volume= 13 | issue= 3 | pages= 224-6 | pmid=5058244 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5058244  }} </ref><ref name="pmid3804928">{{cite journal| author=Foster NK, Martyn JB, Rangno RE, Hogg JC, Pardy RL| title=Leukocytosis of exercise: role of cardiac output and catecholamines. | journal=J Appl Physiol (1985) | year= 1986 | volume= 61 | issue= 6 | pages= 2218-23 | pmid=3804928 | doi=10.1152/jappl.1986.61.6.2218 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3804928  }} </ref><ref name="pmid6444534">{{cite journal| author=Brodeur GM, Dahl GV, Williams DL, Tipton RE, Kalwinsky DK| title=Transient leukemoid reaction and trisomy 21 mosaicism in a phenotypically normal newborn. | journal=Blood | year= 1980 | volume= 55 | issue= 4 | pages= 691-3 | pmid=6444534 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6444534  }} </ref><ref name="pmid28699170">{{cite journal| author=Harvey Y, Bleakley S, Blombery P, Bain BJ| title=Marked leukemoid reaction in a patient with metastatic breast carcinoma. | journal=Am J Hematol | year= 2018 | volume= 93 | issue= 2 | pages= 306-307 | pmid=28699170 | doi=10.1002/ajh.24849 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28699170  }} </ref>:
** Infections - sepsis, scarlet fever, purulent processes, diphtheria, lobar pneumonia, tuberculosis and dysentery.
** [[Infection|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 95: Line 76:
*** After surgical operations and [[splenectomy]].  
*** After surgical operations and [[splenectomy]].  
* Leukemoid reactions of basophilic type:
* Leukemoid reactions of basophilic type:
** 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==


Leukemoid reaction is differentiated from leukemia by following ways:
Leukemoid reaction is differentiated from leukemia by following ways<ref name="pmid16962944">{{cite journal| author=Sakka V, Tsiodras S, Giamarellos-Bourboulis EJ, Giamarellou H| title=An update on the etiology and diagnostic evaluation of a leukemoid reaction. | journal=Eur J Intern Med | year= 2006 | volume= 17 | issue= 6 | pages= 394-8 | pmid=16962944 | doi=10.1016/j.ejim.2006.04.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16962944  }} </ref><ref name="pmid28656128">{{cite journal| author=Updyke KM, Morales-Lappot J, Lee T| title=Atypical Presentation of Chronic Myelogenous Leukemia. | journal=Cureus | year= 2017 | volume= 9 | issue= 5 | pages= e1280 | pmid=28656128 | doi=10.7759/cureus.1280 | pmc=5484601 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28656128  }} </ref>:


{| border="1"
{| class="wikitable" border="1"
|+ Leukemia vs leukemoid reaction
|+ Differential diagnosis of leukemia vs leukemoid reaction
! Differentiating features !! Leukemia !! Leukemoid reaction
! Differentiating features !! Leukemia !! Leukemoid reaction
|-
|-
Line 117: Line 98:
cells to a tumor
cells to a tumor
| Activation of normal hematopoiesis and exit of immature leukocytes
| Activation of normal hematopoiesis and exit of immature leukocytes
into the bloodstream
into the bloodstream
|-
|-
! Duration
! Duration
Line 143: Line 124:
| High
| High
|-
|-
! Toxic granules
! Toxic granules (suggestive of infection)
(suggestive of infection)
| Absent
| Absent
| Present
| Present
Line 152: Line 132:
| Present
| Present
|-
|-
|}
Leukemoid reaction should be differentiated from other causes of leucocytosis. The below table discusses different causes of leucocytosis:
{| class="wikitable"
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Category
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! colspan="4" rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Mechanism
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! colspan="11" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Clinical manifestations
! colspan="8" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Para−clinical findings
! colspan="1" rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptoms
! colspan="6" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Signs
|-
! colspan="8" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab Findings
|-
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physiologic
! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Increased bone marrow production
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demargination of peripheral blood neutrophils
! colspan="1" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Asplenia
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepatosplenomegaly
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lymphadenopathy
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Joint involvement
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |CBC
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |ESR/CRP
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Autonomous
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reactive
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
|-
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hematologic
! align="center" style="background:#DCDCDC;" |[[Granulocytosis|Hereditary neutrophilia]]<ref name="HerringSmith1974">{{cite journal|last1=Herring|first1=William Benjamin|last2=Smith|first2=Laurin Gresham|last3=Walker|first3=Richard Isley|last4=Herion|first4=John Carroll|title=Hereditary neutrophilia|journal=The American Journal of Medicine|volume=56|issue=5|year=1974|pages=729–734|issn=00029343|doi=10.1016/0002-9343(74)90642-1}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Unknown
* Germline [[mutation]] in [[CSF3R]]
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + |Rare [[Dominance relationship|autosomal dominant]] genetic disorder
| align="left" style="background:#F5F5F5;" + |
* Positive family history
| align="center" style="background:#F5F5F5;" + |Normal
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="left" style="background:#F5F5F5;" + |
* Normal [[Granulocyte|granulocytes]]
* [[Histiocyte|Histiocytes]] of Gaucher type
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Molecular testing
| align="left" style="background:#F5F5F5;" + |
* High [[leukocyte alkaline phosphatase]]
* Progress to [[leukemia]]
|-
! align="center" style="background:#DCDCDC;" |[[Myeloproliferative neoplasm|Myeloproliferative neoplasms]]<ref name="pmid20052751">{{cite journal |vauthors=Tefferi A |title=Leukocytosis as a risk factor for thrombosis in myeloproliferative neoplasms-biologically plausible but clinically uncertain |journal=Am. J. Hematol. |volume=85 |issue=2 |pages=93–4 |date=February 2010 |pmid=20052751 |doi=10.1002/ajh.21614 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |
*Unknown
*[[Mutation]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Elderly
| align="left" style="background:#F5F5F5;" + |Exposure to
*[[Chemotherapy]]
*[[Radiation therapy]]
*[[Tobacco smoking|Tobacco smoke]]
| align="left" style="background:#F5F5F5;" + |
* [[Petechia|Petechiae]]
* [[Purpura]]
* Diffuse erythematous [[rash]]
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*[[Shortness of breath]]
*[[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↑/↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑/↓
| align="left" style="background:#F5F5F5;" + |
*Large [[Platelet|platelets]]
*Ovalomacrocytosis
*Basophilic stippling
*[[Howell-Jolly body]]
*Pelger-Huet anomaly
*Ring [[Sideroblastic anemia|sideroblasts]]
| align="left" style="background:#F5F5F5;" + |
*Impaired [[myeloid]] maturation
*[[Congenital dyserythropoietic anemia|Dyserythropoiesis]]
*Dysgranulopoiesis
*Dysmegakaryocytopoiesis
*Hypercellular [[bone marrow]]
*[[Fibrosis]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Bone marrow examination]] + clinical manifestation
| align="left" style="background:#F5F5F5;" + |
*[[Thrombosis]] at unusual sites
*[[Thrombosis]] in younger patients
*Might transformed to [[acute leukemia]]
|-
! align="center" style="background:#DCDCDC;" |[[Polycythemia vera]]<ref name="pmid26336886">{{cite journal |vauthors=Boiocchi L, Gianelli U, Iurlo A, Fend F, Bonzheim I, Cattaneo D, Knowles DM, Orazi A |title=Neutrophilic leukocytosis in advanced stage polycythemia vera: hematopathologic features and prognostic implications |journal=Mod. Pathol. |volume=28 |issue=11 |pages=1448–57 |date=November 2015 |pmid=26336886 |doi=10.1038/modpathol.2015.100 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
*Autonomous [[Red blood cell|erythrocyte]] production
*[[JAK2]] mutation (> 95%)
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Mean age >60 years old
| align="left" style="background:#F5F5F5;" + |
*[[Stroke]]
*[[Visual system|Visual disturbance]]
| align="center" style="background:#F5F5F5;" + |
* Facial [[Hypervolemia|plethora]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*Painful [[erythema]]
| align="center" style="background:#F5F5F5;" + |Nl to ↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
*Elevated normochromic, normocytic [[Red blood cell|RBCs]]
*[[Thrombocytosis]]
*≥ 10% immature myeloid precursors
*Leukoerythroblastic picture
| align="left" style="background:#F5F5F5;" + |
* Increased [[myeloid]]:[[Red blood cell|erythroid]] ratio due to granulocytic proliferation
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Bone marrow examination]] + clinical manifestation
| align="left" style="background:#F5F5F5;" + |
*[[Stroke]]
*[[Venous thrombosis]]
*[[Myelofibrosis]]
*[[Acute leukemia]]
|-
! align="center" style="background:#DCDCDC;" |[[Microangiopathic hemolytic anemia]] (MAHA)<ref name="pmid27288467">{{cite journal |vauthors=Morton JM, George JN |title=Microangiopathic Hemolytic Anemia and Thrombocytopenia in Patients With Cancer |journal=J Oncol Pract |volume=12 |issue=6 |pages=523–30 |date=June 2016 |pmid=27288467 |doi=10.1200/JOP.2016.012096 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Microvascular disease|Microangiopathy]]
* [[Leukemoid reaction]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Coagulopathy|Bleeding disorder]]
* Positive family history
| align="left" style="background:#F5F5F5;" + |
* [[Pallor]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |
*[[Shortness of breath]]
*[[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Fragmented [[Red blood cell|RBCs]]
* [[Red blood cell|Schistocytes]]
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |[[Bone marrow examination]] + clinical manifestation
| align="left" style="background:#F5F5F5;" + |
* Non-immune [[hemolysis]]
* Elevated [[Lactate dehydrogenase|LDH]]
* Elevated [[alkaline phosphatase]]
* Negative [[Coombs test|direct Coomb's test]]
* [[Thrombosis]]
|-
! align="center" style="background:#DCDCDC;" |Leukoerythroblastosis<ref name="pmid25562031">{{cite journal |vauthors=Canbolat Ayhan A, Timur C, Ayhan Y, Kes G |title=Leukoerythroblastosis Mimicking Leukemia: A case report |journal=Iran J Pediatr |volume=24 |issue=3 |pages=332–3 |date=June 2014 |pmid=25562031 |pmc=4276592 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Space-occupying lesions in the [[bone marrow]]
* [[Infection]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Coagulopathy|Bleeding disorder]]
| align="left" style="background:#F5F5F5;" + |
* [[Pallor]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Satiety|Early satiety]]
* [[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
* Nucleated red cells
* [[Reticulocyte|Reticulocytosis]]
* [[Poikilocytosis|Poikilocytes]]
* Circulating immature [[White blood cells|white cells]], generally [[Myelocyte|myelocytes]] and [[Promyelocyte|promyelocytes]]
| align="left" style="background:#F5F5F5;" + |
* Circulating immature [[White blood cells|white cells]], generally [[Myelocyte|myelocytes]] and [[Promyelocyte|promyelocytes]]
* [[Myelofibrosis]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |[[Bone marrow examination|Bone marrow biopsy]]
| align="left" style="background:#F5F5F5;" + |
* [[Bone marrow|Marrow]] infiltrative disorders
* [[Physical trauma|Trauma]]
* [[Sepsis|Septicemia]]
* Massive [[hemolysis]]
* [[Macrocytic anemia|Megaloblastic anemia]]
* [[Hematopoiesis|Extramedullary hematopoiesis]]
|-
! rowspan="12" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Immunology/
Rheumatology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physiologic
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Autonomous increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reactive increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demargination of peripheral blood neutrophils
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Asplenia
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepatosplenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lymphadenopathy
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Joint involvement
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |ESR/CRP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! align="center" style="background:#DCDCDC;" |[[Leukocyte adhesion deficiency]]<ref name="pmid26434744">{{cite journal |vauthors=Levy-Mendelovich S, Rechavi E, Abuzaitoun O, Vernitsky H, Simon AJ, Lev A, Somech R |title=Highlighting the problematic reliance on CD18 for diagnosing leukocyte adhesion deficiency type 1 |journal=Immunol. Res. |volume=64 |issue=2 |pages=476–82 |date=April 2016 |pmid=26434744 |doi=10.1007/s12026-015-8706-5 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Primary immunodeficiency]]
* Failure to express [[CD18]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Rare [[autosomal recessive]], [[Leukocyte adhesion deficiency|LAD]] II more in Middle East and Brazil
| align="left" style="background:#F5F5F5;" + |
* Positive family history
| align="left" style="background:#F5F5F5;" + |
* Characteristic facial appearance, short stature, limb malformations, and severe [[Developmental disability|developmental delay]] in [[Leukocyte adhesion deficiency|LAD]] II
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* Signs of different [[Infection|infections]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓/↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Flow cytometry]]
| align="left" style="background:#F5F5F5;" + |
* Recurrent [[Infection|bacterial infections]]
* Delay in [[umbilical cord]] sloughing
* Inability to form [[Abscess|abscesses]]
|-
! align="center" style="background:#DCDCDC;" |Cryopyrin-associated periodic syndromes<ref name="pmid30035647">{{cite journal |vauthors=Labrousse M, Kevorkian-Verguet C, Boursier G, Rowczenio D, Maurier F, Lazaro E, Aggarwal M, Lemelle I, Mura T, Belot A, Touitou I, Sarrabay G |title=Mosaicism in autoinflammatory diseases: Cryopyrin-associated periodic syndromes (CAPS) and beyond. A systematic review |journal=Crit Rev Clin Lab Sci |volume=55 |issue=6 |pages=432–442 |date=September 2018 |pmid=30035647 |doi=10.1080/10408363.2018.1488805 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Unknown
* [[Mutation]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |[[Dominance relationship|Autosomal dominant]] autoinflammatory syndrome
| align="left" style="background:#F5F5F5;" + |
* Positive family history
| align="left" style="background:#F5F5F5;" + |
* [[Urticaria|Hive]]-like [[rash]] without [[Itch|itching]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* Red eyes
* [[Nausea and vomiting|Vomiting]]
* [[Headache]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓/↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |[[Genetic testing|Genetic tests]]
| align="left" style="background:#F5F5F5;" + |
* [[Blindness]]
* [[Hearing impairment|Hearing loss]]
|-
! align="center" style="background:#DCDCDC;" |[[Rheumatoid arthritis]]<ref name="pmid20870100">{{cite journal |vauthors=Scott DL, Wolfe F, Huizinga TW |title=Rheumatoid arthritis |journal=Lancet |volume=376 |issue=9746 |pages=1094–108 |date=September 2010 |pmid=20870100 |doi=10.1016/S0140-6736(10)60826-4 |url=}}</ref><ref name="pmid24568138">{{cite journal |vauthors=Glant TT, Mikecz K, Rauch TA |title=Epigenetics in the pathogenesis of rheumatoid arthritis |journal=BMC Med |volume=12 |issue= |pages=35 |date=February 2014 |pmid=24568138 |pmc=3936819 |doi=10.1186/1741-7015-12-35 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Immunity (medical)|Immune]] mediated
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any, more in young women, between 30-60 years old
| align="left" style="background:#F5F5F5;" + |
* Positive family history
* [[Smoking|Cigarette smoking]]
* [[Obesity]]
| align="left" style="background:#F5F5F5;" + |
* Deformed [[Joint|joints]]
* [[Rheumatoid nodule|Rheumatoid nodules]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Weight loss]]
* [[Fatigue]]
* [[Dry eyes]] and mouth
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + positive [[Anti-citrullinated protein antibody|anti-CCP antibodies]]
| align="left" style="background:#F5F5F5;" + |
* [[Osteoporosis]]
* [[Infection|Infections]]
* [[Carpal tunnel syndrome]]
* Multi-organ involvement
* [[Lymphoma]]
|-
! align="center" style="background:#DCDCDC;" |[[Juvenile rheumatoid arthritis|Juvenile onset rheumatoid arthritis]]<ref name="pmid23763801">{{cite journal |vauthors=Naz S, Mushtaq A, Rehman S, Bari A, Maqsud A, Khan MZ, Ahmad TM |title=Juvenile rheumatoid arthritis |journal=J Coll Physicians Surg Pak |volume=23 |issue=6 |pages=409–12 |date=June 2013 |pmid=23763801 |doi=06.2013/JCPSP.409412 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Immunity (medical)|Immune]] mediated
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Children under the age of 16
| align="left" style="background:#F5F5F5;" + |
* Positive family history
| align="left" style="background:#F5F5F5;" + |
*Blotchy [[rash]] on a child's arms and legs
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
* [[Dry eyes]] and mouth
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + laboratory findings
| align="left" style="background:#F5F5F5;" + |
* [[Uveitis]]
* [[Infection|Infections]]
* Multi-organ involvement
|-
! align="center" style="background:#DCDCDC;" |[[Still's disease|Adult Still's disease]]<ref name="pmid25613167">{{cite journal |vauthors=Kadavath S, Efthimiou P |title=Adult-onset Still's disease-pathogenesis, clinical manifestations, and new treatment options |journal=Ann. Med. |volume=47 |issue=1 |pages=6–14 |date=February 2015 |pmid=25613167 |doi=10.3109/07853890.2014.971052 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Immunity (medical)|Immune]] mediated
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Rare [[autoimmune disease]]
| align="center" style="background:#F5F5F5;" + |NA
| align="left" style="background:#F5F5F5;" + |
* Nonpruritic salmon-colored [[rash]] (usually over [[trunk]] or [[Limb (anatomy)|extremities]] while [[Fever|febrile]])
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Headache]]
* [[Pharyngitis|Sore throat]]
* [[Weight loss]]
* [[Muscle pain]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Diagnosis of exclusion
| align="left" style="background:#F5F5F5;" + |
* High [[ferritin]]
* Negative [[Antinuclear antibodies|ANA]]
* [[Meningitis|Aseptic meningitis]]
*[[Sensorineural hearing loss]]
|-
! align="center" style="background:#DCDCDC;" |[[Kawasaki disease]]<ref name="pmid25399940">{{cite journal |vauthors=Sundel RP |title=Kawasaki disease |journal=Rheum. Dis. Clin. North Am. |volume=41 |issue=1 |pages=63–73, viii |date=2015 |pmid=25399940 |doi=10.1016/j.rdc.2014.09.010 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Immunity (medical)|Immune]] mediated
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Autoimmune disease]], more in Asian ethnicity boys
| align="center" style="background:#F5F5F5;" + |NA
| align="left" style="background:#F5F5F5;" + |
* Diffuse [[maculopapular]] erythematous [[rash]] in the [[Sex organ|genital]] area, and red [[Eye|eyes]], [[Lip (disambiguation)|lips]], [[Hand|palms]] or [[Sole (foot)|soles]] of the feet
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* Strawberry [[tongue]]
* [[Pharyngitis|Sore throat]]
* [[Diarrhea]]
* Bilateral [[Conjunctiva|conjunctival]] inflammation
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Diagnostic criteria
| align="left" style="background:#F5F5F5;" + |
* Medium-sized-vessel [[vasculitis]]
* [[Coronary artery aneurysm]]
|-
! align="center" style="background:#DCDCDC;" |[[Inflammatory bowel disease|IBD]]<ref name="pmid24415861">{{cite journal |vauthors=Zhang YZ, Li YY |title=Inflammatory bowel disease: pathogenesis |journal=World J. Gastroenterol. |volume=20 |issue=1 |pages=91–9 |date=January 2014 |pmid=24415861 |pmc=3886036 |doi=10.3748/wjg.v20.i1.91 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Immunity (medical)|Immune]] mediated
* [[Mutation]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Autoimmune disease]], more in young
| align="left" style="background:#F5F5F5;" + |
* [[Stress (medicine)|Stress]]
* Positive family history
| align="left" style="background:#F5F5F5;" + |
* [[Pyoderma gangrenosum]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Nausea and vomiting|Vomiting]]
* [[Diarrhea]]
* [[Rectal bleeding]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Colonoscopy]] and [[biopsy]]
| align="left" style="background:#F5F5F5;" + |
* [[Primary sclerosing cholangitis]]
* [[Euthyroid sick syndrome|Non-thyroidal illness syndrome]]
* [[Deep vein thrombosis|DVT]]
* [[Cryptogenic organizing pneumonia|Bronchiolitis obliterans organizing pneumonia]]
|-
! align="center" style="background:#DCDCDC;" |[[Sarcoidosis]]<ref name="pmid25473783">{{cite journal |vauthors=Modaresi Esfeh J, Culver D, Plesec T, John B |title=Clinical presentation and protocol for management of hepatic sarcoidosis |journal=Expert Rev Gastroenterol Hepatol |volume=9 |issue=3 |pages=349–58 |date=March 2015 |pmid=25473783 |doi=10.1586/17474124.2015.958468 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Immunity (medical)|Immune]] mediated
* Unknown
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Autoimmune disease]], more in young African American women
| align="left" style="background:#F5F5F5;" + |
* Positive family history
| align="left" style="background:#F5F5F5;" + |
* [[Rash|Rashes]]
* [[Erythema nodosum]]
* [[Granuloma annulare]]
* [[Lupus pernio]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
Bilateral [[Hilar lymphadenopathy|hilar adenopathy]]
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
* [[Weight loss]]
* [[Blurred vision|Blurry vision]]
* [[Dyspnea|Shortness of breath]]
* [[Cough]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Diagnosis of exclusion
| align="left" style="background:#F5F5F5;" + |
* [[Interstitial lung disease]]
* Systemic [[Inflammation|inflammatory]] disease
|-
! align="center" style="background:#DCDCDC;" |[[Hepatitis|Chronic hepatitis]]<ref name="pmid26092643">{{cite journal |vauthors=Gish RG, Given BD, Lai CL, Locarnini SA, Lau JY, Lewis DL, Schluep T |title=Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities |journal=Antiviral Res. |volume=121 |issue= |pages=47–58 |date=September 2015 |pmid=26092643 |doi=10.1016/j.antiviral.2015.06.008 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Infection]]
* [[Autoimmunity|Autoimmune]]
* [[Ischemia|Ischemic]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Elderly
| align="left" style="background:#F5F5F5;" + |
* [[Alcoholism|Alcohol use]]
* Acute [[infection]]
| align="left" style="background:#F5F5F5;" + |
* [[Jaundice]]
* [[Ascites]] and [[peripheral edema]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
* [[Weight loss]]
* [[Nausea and vomiting]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |[[Liver biopsy]]
| align="left" style="background:#F5F5F5;" + |
* [[Hirsutism]]
* [[Amenorrhea]]
* [[Coagulopathy]]
* [[Hepatic encephalopathy]]
* [[Esophageal varices]]
* [[Hepatorenal syndrome]]
* [[Liver mass|Liver cancer]]
|-
! align="center" style="background:#DCDCDC;" |[[Sweet's syndrome|Sweet syndrome]]<ref name="pmid30247226">{{cite journal |vauthors=Das A, Burmeister R, Chhaya R, Eisenga B, Kumar A |title=Sweet Syndrome in a Patient With Systemic Lupus Erythematosus |journal=J Clin Rheumatol |volume= |issue= |pages= |date=September 2018 |pmid=30247226 |doi=10.1097/RHU.0000000000000904 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Immunity (medical)|Immune]] mediated
* Unknown
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Rare
| align="left" style="background:#F5F5F5;" + |
* [[Relapse]] and [[Remission (medicine)|remission]]
| align="left" style="background:#F5F5F5;" + |
* [[Tenderness (medicine)|Tender]], red, well-demarcated [[Papule|papules]] and [[Plaque|plaques]] on the [[head]], [[neck]], [[Leg|legs]], and arms
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Conjunctivitis]]
* [[Iridocyclitis]]
* [[Aphthous ulcer|Oral aphthae]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="left" style="background:#F5F5F5;" + |
* Papillary and mid-dermal mixed infiltrate of [[Neutrophil|polymorphonuclear]] leukocytes with nuclear fragmentation and [[Histiocytic|histiocytic cells]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Diagnostic criteria
| align="left" style="background:#F5F5F5;" + |
* Cutaneous marker of systemic disease
* [[Acute myeloid leukemia|Acute myelogenous leukemia]]
* Immunologic disease
* Slight increase in [[alkaline phosphatase]]
|-
! align="center" style="background:#DCDCDC;" |[[Gout|Acute gout]]<ref name="pmid24334652">{{cite journal |vauthors=Dalbeth N, Zhong CS, Grainger R, Khanna D, Khanna PP, Singh JA, McQueen FM, Taylor WJ |title=Outcome measures in acute gout: a systematic literature review |journal=J. Rheumatol. |volume=41 |issue=3 |pages=558–68 |date=March 2014 |pmid=24334652 |pmc=4217650 |doi=10.3899/jrheum.131244 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Elevated levels of [[uric acid]] in the [[blood]]
* [[Diet (nutrition)|Diet]]
* [[Genetics|Genetic]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Older males
| align="left" style="background:#F5F5F5;" + |
* [[Alcoholism|Alcohol use]]
* Acute [[infection]]
| align="left" style="background:#F5F5F5;" + |
* [[Tophus|Tophi]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="left" style="background:#F5F5F5;" + |
* [[Arthritis]]
* Urate [[nephropathy]]
|-
! rowspan="6" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Medication
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physiologic
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Autonomous increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reactive increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demargination of peripheral blood neutrophils
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Asplenia
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepatosplenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lymphadenopathy
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Joint involvement
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |ESR/CRP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! align="center" style="background:#DCDCDC;" |[[Steroid]]<ref name="pmid7304648">{{cite journal |vauthors=Shoenfeld Y, Gurewich Y, Gallant LA, Pinkhas J |title=Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis |journal=Am. J. Med. |volume=71 |issue=5 |pages=773–8 |date=November 1981 |pmid=7304648 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Release of [[Granulocyte|granulocytes]] from the [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Steroid]] use
* [[Autoimmune disease]]
* [[Cancer|Malignancy]]
| align="center" style="background:#F5F5F5;" + |
* [[Obesity|Obese]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Abdominal pain]]
* [[Muscle weakness]]
* [[Growth failure]]
* [[Pubertal delay]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Myelofibrosis|Megakaryocytic]]<nowiki/>fragments
* Large numbers of microspherocytes
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + history of drug consumption
| align="left" style="background:#F5F5F5;" + |
* [[Thrombosis|Thromboembolic]]<nowiki/>complications
* [[Cushing's syndrome|Cushing syndrome]]
* [[Diabetes mellitus]]
|-
! align="center" style="background:#DCDCDC;" |[[Filgrastim]] (Myeloid growth factor)<ref name="pmid24142827">{{cite journal |vauthors=Crawford J, Armitage J, Balducci L, Becker PS, Blayney DW, Cataland SR, Heaney ML, Hudock S, Kloth DD, Kuter DJ, Lyman GH, McMahon B, Rugo HS, Saad AA, Schwartzberg LS, Shayani S, Steensma DP, Talbott M, Vadhan-Raj S, Westervelt P, Westmoreland M, Dwyer M, Ho M |title=Myeloid growth factors |journal=J Natl Compr Canc Netw |volume=11 |issue=10 |pages=1266–90 |date=October 2013 |pmid=24142827 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Release of [[Granulocyte|granulocytes]] from the [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Cancer|Malignancy]]
* [[Neutropenia]]
| align="left" style="background:#F5F5F5;" + |
* [[Alopecia|Hair loss]]
* Local skin reactions at the site of [[Injection (medicine)|injection]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Cough]]
* [[Chest pain]]
* [[Nausea and vomiting|Vomiting]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="left" style="background:#F5F5F5;" + |Clinical manifestation + history of drug consumption
| align="left" style="background:#F5F5F5;" + |
* [[Alveolus|Alveolar]] hemorrhage
* [[Acute respiratory distress syndrome]]
|-
! align="center" style="background:#DCDCDC;" |[[Lithium]]<ref name="pmid25735990">{{cite journal |vauthors=Aiff H, Attman PO, Aurell M, Bendz H, Ramsauer B, Schön S, Svedlund J |title=Effects of 10 to 30 years of lithium treatment on kidney function |journal=J. Psychopharmacol. (Oxford) |volume=29 |issue=5 |pages=608–14 |date=May 2015 |pmid=25735990 |doi=10.1177/0269881115573808 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Unknown
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Bipolar disorder]]
| align="left" style="background:#F5F5F5;" + |
* [[Weight gain]]
* [[Acne vulgaris|Acne]]
* Hand [[tremor]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Confusion]]
* [[Constipation]] or [[diarrhea]]
* Decreased [[memory]]
* [[Xerostomia|Dry mouth]]
* [[Muscle weakness]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + history of drug consumption
| align="left" style="background:#F5F5F5;" + |
* [[Extrapyramidal system|Extrapyramidal side effects]]
* [[Goitre|Euthyroid goitre]]
* [[Hypothyroidism]]
* [[Renal insufficiency|Kidney damage]]
|-
! align="center" style="background:#DCDCDC;" |[[Catecholamine|Catecholamines]]
([[epinephrine]])<ref name="pmid12417430">{{cite journal |vauthors=Bedoui S, Lechner S, Gebhardt T, Nave H, Beck-Sickinger AG, Straub RH, Pabst R, von Hörsten S |title=NPY modulates epinephrine-induced leukocytosis via Y-1 and Y-5 receptor activation in vivo: sympathetic co-transmission during leukocyte mobilization |journal=J. Neuroimmunol. |volume=132 |issue=1-2 |pages=25–33 |date=November 2002 |pmid=12417430 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Stimulation of [[bone marrow]] myelopoiesis
* Egress into the circulation
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Anaphylaxis]]
* [[Respiratory disease|Respiratory diseases]]
| align="left" style="background:#F5F5F5;" + |
* Acutely ill
* [[Diaphoresis|Diaphoretic]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Dizziness]]
* [[Tremor]]
* [[Anxiety]]
* [[Dyspnea]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Myelofibrosis|Megakaryocytic]]<nowiki/>fragments
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + history of drug consumption
| align="left" style="background:#F5F5F5;" + |
* [[Thrombosis|Thromboembolic]]<nowiki/>complications
|-
! align="center" style="background:#DCDCDC;" |[[Tretinoin|ATRA]]<ref name="pmid17257495">{{cite journal |vauthors=Bi KH, Jiang GS |title=Relationship between cytokines and leukocytosis in patients with APL induced by all-trans retinoic acid or arsenic trioxide |journal=Cell. Mol. Immunol. |volume=3 |issue=6 |pages=421–7 |date=December 2006 |pmid=17257495 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Differentiating [[Promyelocyte|promyelocytes]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Acne vulgaris|Acne]]
* [[Acute promyelocytic leukemia]]
| align="left" style="background:#F5F5F5;" + |
* [[Xeroderma|Skin dryness]]
* [[Alopecia|Hair loss]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Dyspnea|Shortness of breath]]
* [[Headache]]
* [[Paresthesia|Numbness]]
* [[Depression]]
* [[Itch|Itchiness]]
* [[Nausea and vomiting|Vomiting]]
* [[Myalgia|Muscle pain]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + history of drug consumption
| align="left" style="background:#F5F5F5;" + |
* [[Teratology|Teratogen]]
* [[Thrombosis]]
* [[Idiopathic intracranial hypertension|Benign intracranial hypertension]]
* [[Hyperlipoproteinemia|Hypercholesterolemia]]
* [[Liver|Liver damage]]
|-
! rowspan="10" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physiologic
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Autonomous increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reactive increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demargination of peripheral blood neutrophils
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Asplenia
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepatosplenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lymphadenopathy
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Joint involvement
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |ESR/CRP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! align="center" style="background:#DCDCDC;" |[[Infection|Infections]]<ref name="pmid24012414">{{cite journal |vauthors=Horasan ES, Dağ A, Ersoz G, Kaya A |title=Surgical site infections and mortality in elderly patients |journal=Med Mal Infect |volume=43 |issue=10 |pages=417–22 |date=October 2013 |pmid=24012414 |doi=10.1016/j.medmal.2013.07.009 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |
* [[Infection]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* Close contact
* [[Immunodeficiency]]
| align="left" style="background:#F5F5F5;" + |
* Acutely ill
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |±
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
* [[Nausea and vomiting]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Howell-Jolly body|Howell-Jolly bodies]]
* Nucleated [[Red blood cell|RBCs]]
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation+ culture
| align="left" style="background:#F5F5F5;" + |
* Depends on etiology
|-
! align="center" style="background:#DCDCDC;" |[[Allergy]]<ref name="pmid29871797">{{cite journal |vauthors=Davis MDP, van der Hilst JCH |title=Mimickers of Urticaria: Urticarial Vasculitis and Autoinflammatory Diseases |journal=J Allergy Clin Immunol Pract |volume=6 |issue=4 |pages=1162–1170 |date=2018 |pmid=29871797 |doi=10.1016/j.jaip.2018.05.006 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Unknown
* Activation of [[chloride]] transport
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Anaphylaxis]]
* [[Respiratory|Respiratory diseases]]
| align="left" style="background:#F5F5F5;" + |
* Acutely ill
* [[Diaphoresis|Diaphoretic]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Dizziness]]
* [[Tremor]]
* [[Anxiety]]
* [[Dyspnea]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Myelofibrosis|Megakaryocytic]]<nowiki/>fragments
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |Post [[splenectomy]]<ref name="pmid29766137">{{cite journal |vauthors=Bilello JF, Sharp VL, Dirks RC, Kaups KL, Davis JW |title=After the embo: predicting non-hemorrhagic indications for splenectomy after angioembolization in patients with blunt trauma |journal=Trauma Surg Acute Care Open |volume=3 |issue=1 |pages=e000159 |date=2018 |pmid=29766137 |pmc=5887792 |doi=10.1136/tsaco-2017-000159 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Unknown
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* Prior surgical removal of the [[spleen]]
* [[Sickle-cell disease|Sickle cell disease]]
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Howell-Jolly body|Howell-Jolly bodies]]
* Nucleated [[Red blood cell|RBCs]]
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="left" style="background:#F5F5F5;" + |
* Incidental laboratory finding
* [[Thrombosis]]
|-
! align="center" style="background:#DCDCDC;" |[[Smoking|Cigarette smoking]]<ref name="pmid27688691">{{cite journal |vauthors=Lymperaki E, Makedou K, Iliadis S, Vagdatli E |title=Effects of acute cigarette smoking on total blood count and markers of oxidative stress in active and passive smokers |journal=Hippokratia |volume=19 |issue=4 |pages=293–7 |date=2015 |pmid=27688691 |pmc=5033137 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Reduced [[Blood plasma|plasma]] volume
* Accelerated [[erythropoiesis]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Smoking|Cigarette smoking]]
| align="left" style="background:#F5F5F5;" + |
* [[Cyanosis]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Cough]]
* [[Dyspnea]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |[[Stress (medicine)|Stress]]/[[Physical exercise|exercise]]<ref name="pmid26477922">{{cite journal |vauthors=Simpson RJ, Kunz H, Agha N, Graff R |title=Exercise and the Regulation of Immune Functions |journal=Prog Mol Biol Transl Sci |volume=135 |issue= |pages=355–80 |date=2015 |pmid=26477922 |doi=10.1016/bs.pmbts.2015.08.001 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Reduced plasma volume
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Athlete
| align="left" style="background:#F5F5F5;" + |
* [[Physical exercise|Exercise]]
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Howell-Jolly body|Howell-Jolly bodies]]
* Nucleated [[Red blood cell|RBCs]]
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |[[Infant|Infancy]]<ref name="pmid26580401">{{cite journal |vauthors=Nouatin O, Gbédandé K, Ibitokou S, Vianou B, Houngbegnon P, Ezinmegnon S, Borgella S, Akplogan C, Cottrell G, Varani S, Massougbodji A, Moutairou K, Troye-Blomberg M, Deloron P, Luty AJ, Fievet N |title=Infants' Peripheral Blood Lymphocyte Composition Reflects Both Maternal and Post-Natal Infection with Plasmodium falciparum |journal=PLoS ONE |volume=10 |issue=11 |pages=e0139606 |date=2015 |pmid=26580401 |pmc=4651557 |doi=10.1371/journal.pone.0139606 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |Physiologic
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Infant|Infancy]]
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |[[Pregnancy]]<ref name="pmid26621538">{{cite journal |vauthors=Perseghin P |title=Erythrocyte exchange and leukapheresis in pregnancy |journal=Transfus. Apher. Sci. |volume=53 |issue=3 |pages=279–82 |date=December 2015 |pmid=26621538 |doi=10.1016/j.transci.2015.11.007 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |Physiologic
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Pregnancy]]
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |[[Platelet]] clumping<ref name="pmid25369589">{{cite journal |vauthors=Castrillo A, Álvarez I, Tolksdorf F |title=In vitro evaluation of platelet concentrates suspended in additive solution and treated for pathogen reduction: effects of clumping formation |journal=Blood Transfus |volume=13 |issue=2 |pages=281–6 |date=April 2015 |pmid=25369589 |pmc=4385077 |doi=10.2450/2014.0162-14 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |Spurious
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Cytoplasm|Cytoplasmic]] fragments
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |[[Cryoglobulinemia|Mixed cryoglobulinemia]]<ref name="pmid25837517">{{cite journal |vauthors=Cacoub P, Comarmond C, Domont F, Savey L, Saadoun D |title=Cryoglobulinemia Vasculitis |journal=Am. J. Med. |volume=128 |issue=9 |pages=950–5 |date=September 2015 |pmid=25837517 |doi=10.1016/j.amjmed.2015.02.017 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |Spurious
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Cancer|Malignancy]]
* [[Autoimmune disease]]
* [[Infection]]
| align="left" style="background:#F5F5F5;" + |
* Atypical cutaneous [[Ulcer|ulcers]]
* Palpable [[purpura]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Headache]]
* [[Confusion]]
* Blurry or loss of [[Visual system|vision]]
* Generalized [[Muscle weakness|weakness]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Cytoplasm|Cytoplasmic]] fragments
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Skin biopsy]]
| align="left" style="background:#F5F5F5;" + |
* [[Vasculitis]]
* [[Neuropathy]]
* [[Raynaud's phenomenon|Raynaud phenomenon]]
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Category
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physiologic
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Autonomous increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reactive increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demargination of peripheral blood neutrophils
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Asplenia
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepatosplenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lymphadenopathy
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Joint involvement
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |ESR/CRP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|}
|}


==Epidemiology and Demographics==
==Epidemiology and Demographics==
=== Age ===
* Patients of all age groups may develop leukemoid reaction<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><ref name="pmid29696475">{{cite journal| author=Hoofien A, Yarden-Bilavski H, Ashkenazi S, Chodick G, Livni G| title=Leukemoid reaction in the pediatric population: etiologies, outcome, and implications. | journal=Eur J Pediatr | year= 2018 | volume= 177 | issue= 7 | pages= 1029-1036 | pmid=29696475 | doi=10.1007/s00431-018-3155-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29696475  }} </ref>.
* Normal [[White blood cells|white blood cell count]] 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 have the following complaints<ref name="pmid29366572">{{cite journal| author=Ellison TA, Mandal K| title=Leukemoid reaction: Case report. | journal=J Thorac Cardiovasc Surg | year= 2018 | volume= 155 | issue= 4 | pages= e117-e118 | pmid=29366572 | doi=10.1016/j.jtcvs.2017.08.125 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29366572  }} </ref><ref name="pmid27720771">{{cite journal| author=Wang Z, Cai Q, Li G, Jiang N, Niu Y| title=Giant Pheochromocytoma With Leukemoid Reaction: A Case Report. | journal=Urology | year= 2017 | volume= 99 | issue=  | pages= e17-e19 | pmid=27720771 | doi=10.1016/j.urology.2016.08.021 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27720771  }} </ref>
*Early clinical features, include:
**[[Fever]]
**[[Hyperhidrosis]]
**[[Fatigue]]
===Complications===
===Complications===
*Common complications of leukemoid reaction, include:
**[[Tumor lysis syndrome]]
**[[Disseminated intravascular coagulation|Disseminated intravascular coagulopathy]]
**[[Acute respiratory failure]]
**[[Pulmonary hemorrhage]]
**[[Stroke|CNS infarction]]
**[[Splenic infarction]]
**[[Myocardial ischemia]]
**[[Renal failure]]


===Prognosis===
=== Prognosis ===
 
*Prognosis generally depends on the underlying etiologies.
*If the [[Neutrophil|white blood cell count]] reaches more than 50,000 per mm3, life threatening complications can occur.
==Diagnosis==
==Diagnosis==
===Diagnostic Criteria===
===Symptoms===
 
*Leukemoid reaction is usually symptomatic.
===History and Symptoms===
*Symptoms of leukemoid reaction are often unspecific, such as<ref name="pmid27057215">{{cite journal| author=Agrawal D, Kurwale N, Sharma BS| title=Leukocytosis after routine cranial surgery: A potential marker for brain damage in intracranial surgery. | journal=Asian J Neurosurg | year= 2016 | volume= 11 | issue= 2 | pages= 109-13 | pmid=27057215 | doi=10.4103/1793-5482.145066 | pmc=4802930 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27057215  }} </ref>:
**[[Weight loss]]
**[[Fevers of unknown origin]]
**[[Hyperhidrosis]]
**Chronic [[pain]]
**[[Fatigue]]
**[[Dyspnea]]
**[[Malaise]]


===Physical Examination===
*Obtain history of the following:
**Clinical features
**Duration (e.g. days, weeks, months)
**Remainder of [[complete blood count]]


===Laboratory Findings===
=== Laboratory findings ===
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.
*Laboratory findings consistent with the diagnosis of leukemoid reaction, include:<ref name="pmid29366572">{{cite journal| author=Ellison TA, Mandal K| title=Leukemoid reaction: Case report. | journal=J Thorac Cardiovasc Surg | year= 2018 | volume= 155 | issue= 4 | pages= e117-e118 | pmid=29366572 | doi=10.1016/j.jtcvs.2017.08.125 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29366572  }} </ref>:
 
**[[White blood cell count]] above the normal range, greater than 25,000 per mm<sup>3</sup>.
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.
**[[Bone marrow aspiration]] revealing hyperplasia of normal [[Hematopoiesis|hematopoietic]] cells in proliferative reactions.
 
**Presence of blast and immature forms of [[leukocyte]], [[platelet]] and [[Red blood cell|erythrocytes]] in the proliferative reactions.
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.
**Peripheral blood smear showing [[myelocyte]]s, [[metamyelocyte]]s, [[promyelocyte]]s, and few [[myeloblasts|myeloblasts.]]
**[[Leukocyte alkaline phosphatase]] score 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===
===Echocardiography 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.<ref name="pmid29366572">{{cite journal| author=Ellison TA, Mandal K| title=Leukemoid reaction: Case report. | journal=J Thorac Cardiovasc Surg | year= 2018 | volume= 155 | issue= 4 | pages= e117-e118 | pmid=29366572 | doi=10.1016/j.jtcvs.2017.08.125 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29366572  }} </ref>
* 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. In general, there is no role for surgery.


===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==

Latest revision as of 06:58, 2 February 2019

WikiDoc Resources for Leukemoid reaction

Articles

Most recent articles on Leukemoid reaction

Most cited articles on Leukemoid reaction

Review articles on Leukemoid reaction

Articles on Leukemoid reaction in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Leukemoid reaction

Images of Leukemoid reaction

Photos of Leukemoid reaction

Podcasts & MP3s on Leukemoid reaction

Videos on Leukemoid reaction

Evidence Based Medicine

Cochrane Collaboration on Leukemoid reaction

Bandolier on Leukemoid reaction

TRIP on Leukemoid reaction

Clinical Trials

Ongoing Trials on Leukemoid reaction at Clinical Trials.gov

Trial results on Leukemoid reaction

Clinical Trials on Leukemoid reaction at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Leukemoid reaction

NICE Guidance on Leukemoid reaction

NHS PRODIGY Guidance

FDA on Leukemoid reaction

CDC on Leukemoid reaction

Books

Books on Leukemoid reaction

News

Leukemoid reaction in the news

Be alerted to news on Leukemoid reaction

News trends on Leukemoid reaction

Commentary

Blogs on Leukemoid reaction

Definitions

Definitions of Leukemoid reaction

Patient Resources / Community

Patient resources on Leukemoid reaction

Discussion groups on Leukemoid reaction

Patient Handouts on Leukemoid reaction

Directions to Hospitals Treating Leukemoid reaction

Risk calculators and risk factors for Leukemoid reaction

Healthcare Provider Resources

Symptoms of Leukemoid reaction

Causes & Risk Factors for Leukemoid reaction

Diagnostic studies for Leukemoid reaction

Treatment of Leukemoid reaction

Continuing Medical Education (CME)

CME Programs on Leukemoid reaction

International

Leukemoid reaction en Espanol

Leukemoid reaction en Francais

Business

Leukemoid reaction in the Marketplace

Patents on Leukemoid reaction

Experimental / Informatics

List of terms related to Leukemoid reaction

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2] Associate Editor(s)-in-Chief: Jogeet Singh Sekhon, M.D. [3]

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 25,000-30,000 per mm3 . Leukocytosis is increase in white blood cell count of more than 10,000 per mm3 and when the count exceeds 25,000 per mm3, 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].

Pathophysiology

Hematopoietic growth factors in leukocytosis, By Hematopoietic_growth_factors.svg: Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007) Rang & Dale's pharmacology, Churchill Livingstone ISBN: 0-443-06911-5.User:Mikael Häggström and A. Radderivative work: Furfur - This file was derived from: Hematopoietic growth factors.svg:, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=31083166


Causes

Differentiating Leukemoid reaction from Other Diseases

Leukemoid reaction is differentiated from leukemia by following ways[11][12]:

Differential diagnosis of 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

Leukemoid reaction should be differentiated from other causes of leucocytosis. The below table discusses different causes of leucocytosis:

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[13] + + Rare autosomal dominant genetic disorder
  • Positive family history
Normal Nl + Nl Nl Nl Nl Nl Nl Molecular testing
Myeloproliferative neoplasms[14] + + + Elderly Exposure to ± + Nl + ↑/↓ ↑/↓ Nl Nl Bone marrow examination + clinical manifestation
Polycythemia vera[15] + + 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)[16] + + + Any + + + NA Bone marrow examination + clinical manifestation
Leukoerythroblastosis[17] + + 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[18] + + 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[19] + + Autosomal dominant autoinflammatory syndrome
  • Positive family history
+ Nl + ↓/↑
  • Leukocytosis
  • Leukocytosis
Nl Genetic tests
Rheumatoid arthritis[20][21] + + 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[22] + + 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[23] + + Rare autoimmune disease NA + Nl + +
  • Leukocytosis
NA Nl Nl Diagnosis of exclusion
Kawasaki disease[24] + + Autoimmune disease, more in Asian ethnicity boys NA + + Nl + +
  • Leukocytosis
NA Nl Nl Diagnostic criteria
IBD[25] + + Autoimmune disease, more in young
  • Stress
  • Positive family history
+ + Nl + + +
  • Leukocytosis
NA Nl Nl Colonoscopy and biopsy
Sarcoidosis[26] + + Autoimmune disease, more in young African American women
  • Positive family history
+ + Nl + +

Bilateral hilar adenopathy

+
  • Leukocytosis
NA Nl Nl Diagnosis of exclusion
Chronic hepatitis[27] + + Elderly + + + + +
  • Leukocytosis
NA Liver biopsy
Sweet syndrome[28] + + Rare + + Nl + +
  • Leukocytosis
Nl Nl Diagnostic criteria
Acute gout[29] + + 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[30] + + + Any + Nl to ↓ Nl to ↓ Nl Clinical manifestation + history of drug consumption
Filgrastim (Myeloid growth factor)[31] + + + Any + Nl to ↓ + Nl to ↓ NA NA Nl Nl Clinical manifestation + history of drug consumption
Lithium[32]
  • Unknown
+ + + Any Nl Nl to ↓ NA NA Nl Nl Clinical manifestation + history of drug consumption
Catecholamines

(epinephrine)[33]

  • Stimulation of bone marrow myelopoiesis
  • Egress into the circulation
+ + + Any Nl to ↓ Nl Nl Clinical manifestation + history of drug consumption
ATRA[34] + + + 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[35] + + + + Any
  • Acutely ill
+ + Nl to ↓ ± ± ± Nl Nl Clinical manifestation+ culture
  • Depends on etiology
Allergy[36]
  • Unknown
  • Activation of chloride transport
+ + + + Any Nl to ↓ Nl Nl Clinical manifestation
Post splenectomy[37]
  • Unknown
+ + + Any
  • Normal
± Nl + Nl Nl Clinical manifestation
Cigarette smoking[38] + + + Any Nl NA NA Nl Nl Nl Clinical manifestation
Stress/exercise[39]
  • Reduced plasma volume
+ + + Athlete
  • Normal
Nl Nl Nl Clinical manifestation
Infancy[40] Physiologic + + Infancy
  • Normal
Nl NA NA Nl Nl Nl Clinical manifestation
Pregnancy[41] Physiologic + + Pregnancy
  • Normal
Nl NA NA Nl Nl Nl Clinical manifestation
Platelet clumping[42] Spurious + Any
  • Normal
Nl Nl Nl Nl Nl Nl Clinical manifestation
Mixed cryoglobulinemia[43] 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

Epidemiology and Demographics

Age

  • Patients of all age groups may develop leukemoid reaction[1][44].
  • Normal white blood cell count 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

Screening

No screening is done for leukemoid reaction.

Natural History, Complications, and Prognosis

History

The majority of patients with leukemoid reaction have the following complaints[45][46]

Complications

Prognosis

  • Prognosis generally depends on the underlying etiologies.
  • If the white blood cell count reaches more than 50,000 per mm3, life threatening complications can occur.

Diagnosis

Symptoms

  • Obtain history of the following:

Laboratory findings

Electrocardiogram

No specific ECG changes in leukemoid reaction.

X-Ray

No specific x ray changes in leukemoid reaction.

Echocardiography 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. In general, there is no role for surgery.

Primary prevention

Prevention and treatment of infections.

Secondary prevention

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

See also

References

  1. 1.0 1.1 1.2 1.3 Abramson N, Melton B (2000). "Leukocytosis: basics of clinical assessment". Am Fam Physician. 62 (9): 2053–60. PMID 11087187.
  2. Ward HN, Reinhard EH (1971). "Chronic idiopathic leukocytosis". Ann Intern Med. 75 (2): 193–8. PMID 5558646.
  3. Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016
  4. Wanahita A, Goldsmith EA, Musher DM (2002). "Conditions associated with leukocytosis in a tertiary care hospital, with particular attention to the role of infection caused by clostridium difficile". Clin Infect Dis. 34 (12): 1585–92. doi:10.1086/340536. PMID 12032893.
  5. Lawrence YR, Raveh D, Rudensky B, Munter G (2007). "Extreme leukocytosis in the emergency department". QJM. 100 (4): 217–23. doi:10.1093/qjmed/hcm006. PMID 17314214.
  6. McBride JA, Dacie JV, Shapley R (1968). "The effect of splenectomy on the leucocyte count". Br J Haematol. 14 (2): 225–31. PMID 5635603.
  7. Spencer RP, McPhedran P, Finch SC, Morgan WS (1972). "Persistent neutrophilic leukocytosis associated with idiopathic functional asplenia". J Nucl Med. 13 (3): 224–6. PMID 5058244.
  8. Foster NK, Martyn JB, Rangno RE, Hogg JC, Pardy RL (1986). "Leukocytosis of exercise: role of cardiac output and catecholamines". J Appl Physiol (1985). 61 (6): 2218–23. doi:10.1152/jappl.1986.61.6.2218. PMID 3804928.
  9. Brodeur GM, Dahl GV, Williams DL, Tipton RE, Kalwinsky DK (1980). "Transient leukemoid reaction and trisomy 21 mosaicism in a phenotypically normal newborn". Blood. 55 (4): 691–3. PMID 6444534.
  10. Harvey Y, Bleakley S, Blombery P, Bain BJ (2018). "Marked leukemoid reaction in a patient with metastatic breast carcinoma". Am J Hematol. 93 (2): 306–307. doi:10.1002/ajh.24849. PMID 28699170.
  11. Sakka V, Tsiodras S, Giamarellos-Bourboulis EJ, Giamarellou H (2006). "An update on the etiology and diagnostic evaluation of a leukemoid reaction". Eur J Intern Med. 17 (6): 394–8. doi:10.1016/j.ejim.2006.04.004. PMID 16962944.
  12. Updyke KM, Morales-Lappot J, Lee T (2017). "Atypical Presentation of Chronic Myelogenous Leukemia". Cureus. 9 (5): e1280. doi:10.7759/cureus.1280. PMC 5484601. PMID 28656128.
  13. Herring, William Benjamin; Smith, Laurin Gresham; Walker, Richard Isley; Herion, John Carroll (1974). "Hereditary neutrophilia". The American Journal of Medicine. 56 (5): 729–734. doi:10.1016/0002-9343(74)90642-1. ISSN 0002-9343.
  14. Tefferi A (February 2010). "Leukocytosis as a risk factor for thrombosis in myeloproliferative neoplasms-biologically plausible but clinically uncertain". Am. J. Hematol. 85 (2): 93–4. doi:10.1002/ajh.21614. PMID 20052751.
  15. Boiocchi L, Gianelli U, Iurlo A, Fend F, Bonzheim I, Cattaneo D, Knowles DM, Orazi A (November 2015). "Neutrophilic leukocytosis in advanced stage polycythemia vera: hematopathologic features and prognostic implications". Mod. Pathol. 28 (11): 1448–57. doi:10.1038/modpathol.2015.100. PMID 26336886.
  16. Morton JM, George JN (June 2016). "Microangiopathic Hemolytic Anemia and Thrombocytopenia in Patients With Cancer". J Oncol Pract. 12 (6): 523–30. doi:10.1200/JOP.2016.012096. PMID 27288467.
  17. Canbolat Ayhan A, Timur C, Ayhan Y, Kes G (June 2014). "Leukoerythroblastosis Mimicking Leukemia: A case report". Iran J Pediatr. 24 (3): 332–3. PMC 4276592. PMID 25562031.
  18. Levy-Mendelovich S, Rechavi E, Abuzaitoun O, Vernitsky H, Simon AJ, Lev A, Somech R (April 2016). "Highlighting the problematic reliance on CD18 for diagnosing leukocyte adhesion deficiency type 1". Immunol. Res. 64 (2): 476–82. doi:10.1007/s12026-015-8706-5. PMID 26434744.
  19. Labrousse M, Kevorkian-Verguet C, Boursier G, Rowczenio D, Maurier F, Lazaro E, Aggarwal M, Lemelle I, Mura T, Belot A, Touitou I, Sarrabay G (September 2018). "Mosaicism in autoinflammatory diseases: Cryopyrin-associated periodic syndromes (CAPS) and beyond. A systematic review". Crit Rev Clin Lab Sci. 55 (6): 432–442. doi:10.1080/10408363.2018.1488805. PMID 30035647.
  20. Scott DL, Wolfe F, Huizinga TW (September 2010). "Rheumatoid arthritis". Lancet. 376 (9746): 1094–108. doi:10.1016/S0140-6736(10)60826-4. PMID 20870100.
  21. Glant TT, Mikecz K, Rauch TA (February 2014). "Epigenetics in the pathogenesis of rheumatoid arthritis". BMC Med. 12: 35. doi:10.1186/1741-7015-12-35. PMC 3936819. PMID 24568138.
  22. Naz S, Mushtaq A, Rehman S, Bari A, Maqsud A, Khan MZ, Ahmad TM (June 2013). "Juvenile rheumatoid arthritis". J Coll Physicians Surg Pak. 23 (6): 409–12. doi:06.2013/JCPSP.409412 Check |doi= value (help). PMID 23763801.
  23. Kadavath S, Efthimiou P (February 2015). "Adult-onset Still's disease-pathogenesis, clinical manifestations, and new treatment options". Ann. Med. 47 (1): 6–14. doi:10.3109/07853890.2014.971052. PMID 25613167.
  24. Sundel RP (2015). "Kawasaki disease". Rheum. Dis. Clin. North Am. 41 (1): 63–73, viii. doi:10.1016/j.rdc.2014.09.010. PMID 25399940.
  25. Zhang YZ, Li YY (January 2014). "Inflammatory bowel disease: pathogenesis". World J. Gastroenterol. 20 (1): 91–9. doi:10.3748/wjg.v20.i1.91. PMC 3886036. PMID 24415861.
  26. Modaresi Esfeh J, Culver D, Plesec T, John B (March 2015). "Clinical presentation and protocol for management of hepatic sarcoidosis". Expert Rev Gastroenterol Hepatol. 9 (3): 349–58. doi:10.1586/17474124.2015.958468. PMID 25473783.
  27. Gish RG, Given BD, Lai CL, Locarnini SA, Lau JY, Lewis DL, Schluep T (September 2015). "Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities". Antiviral Res. 121: 47–58. doi:10.1016/j.antiviral.2015.06.008. PMID 26092643.
  28. Das A, Burmeister R, Chhaya R, Eisenga B, Kumar A (September 2018). "Sweet Syndrome in a Patient With Systemic Lupus Erythematosus". J Clin Rheumatol. doi:10.1097/RHU.0000000000000904. PMID 30247226.
  29. Dalbeth N, Zhong CS, Grainger R, Khanna D, Khanna PP, Singh JA, McQueen FM, Taylor WJ (March 2014). "Outcome measures in acute gout: a systematic literature review". J. Rheumatol. 41 (3): 558–68. doi:10.3899/jrheum.131244. PMC 4217650. PMID 24334652.
  30. Shoenfeld Y, Gurewich Y, Gallant LA, Pinkhas J (November 1981). "Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis". Am. J. Med. 71 (5): 773–8. PMID 7304648.
  31. Crawford J, Armitage J, Balducci L, Becker PS, Blayney DW, Cataland SR, Heaney ML, Hudock S, Kloth DD, Kuter DJ, Lyman GH, McMahon B, Rugo HS, Saad AA, Schwartzberg LS, Shayani S, Steensma DP, Talbott M, Vadhan-Raj S, Westervelt P, Westmoreland M, Dwyer M, Ho M (October 2013). "Myeloid growth factors". J Natl Compr Canc Netw. 11 (10): 1266–90. PMID 24142827.
  32. Aiff H, Attman PO, Aurell M, Bendz H, Ramsauer B, Schön S, Svedlund J (May 2015). "Effects of 10 to 30 years of lithium treatment on kidney function". J. Psychopharmacol. (Oxford). 29 (5): 608–14. doi:10.1177/0269881115573808. PMID 25735990.
  33. Bedoui S, Lechner S, Gebhardt T, Nave H, Beck-Sickinger AG, Straub RH, Pabst R, von Hörsten S (November 2002). "NPY modulates epinephrine-induced leukocytosis via Y-1 and Y-5 receptor activation in vivo: sympathetic co-transmission during leukocyte mobilization". J. Neuroimmunol. 132 (1–2): 25–33. PMID 12417430.
  34. Bi KH, Jiang GS (December 2006). "Relationship between cytokines and leukocytosis in patients with APL induced by all-trans retinoic acid or arsenic trioxide". Cell. Mol. Immunol. 3 (6): 421–7. PMID 17257495.
  35. Horasan ES, Dağ A, Ersoz G, Kaya A (October 2013). "Surgical site infections and mortality in elderly patients". Med Mal Infect. 43 (10): 417–22. doi:10.1016/j.medmal.2013.07.009. PMID 24012414.
  36. Davis M, van der Hilst J (2018). "Mimickers of Urticaria: Urticarial Vasculitis and Autoinflammatory Diseases". J Allergy Clin Immunol Pract. 6 (4): 1162–1170. doi:10.1016/j.jaip.2018.05.006. PMID 29871797. Vancouver style error: initials (help)
  37. Bilello JF, Sharp VL, Dirks RC, Kaups KL, Davis JW (2018). "After the embo: predicting non-hemorrhagic indications for splenectomy after angioembolization in patients with blunt trauma". Trauma Surg Acute Care Open. 3 (1): e000159. doi:10.1136/tsaco-2017-000159. PMC 5887792. PMID 29766137.
  38. Lymperaki E, Makedou K, Iliadis S, Vagdatli E (2015). "Effects of acute cigarette smoking on total blood count and markers of oxidative stress in active and passive smokers". Hippokratia. 19 (4): 293–7. PMC 5033137. PMID 27688691.
  39. Simpson RJ, Kunz H, Agha N, Graff R (2015). "Exercise and the Regulation of Immune Functions". Prog Mol Biol Transl Sci. 135: 355–80. doi:10.1016/bs.pmbts.2015.08.001. PMID 26477922.
  40. Nouatin O, Gbédandé K, Ibitokou S, Vianou B, Houngbegnon P, Ezinmegnon S, Borgella S, Akplogan C, Cottrell G, Varani S, Massougbodji A, Moutairou K, Troye-Blomberg M, Deloron P, Luty AJ, Fievet N (2015). "Infants' Peripheral Blood Lymphocyte Composition Reflects Both Maternal and Post-Natal Infection with Plasmodium falciparum". PLoS ONE. 10 (11): e0139606. doi:10.1371/journal.pone.0139606. PMC 4651557. PMID 26580401.
  41. Perseghin P (December 2015). "Erythrocyte exchange and leukapheresis in pregnancy". Transfus. Apher. Sci. 53 (3): 279–82. doi:10.1016/j.transci.2015.11.007. PMID 26621538.
  42. Castrillo A, Álvarez I, Tolksdorf F (April 2015). "In vitro evaluation of platelet concentrates suspended in additive solution and treated for pathogen reduction: effects of clumping formation". Blood Transfus. 13 (2): 281–6. doi:10.2450/2014.0162-14. PMC 4385077. PMID 25369589.
  43. Cacoub P, Comarmond C, Domont F, Savey L, Saadoun D (September 2015). "Cryoglobulinemia Vasculitis". Am. J. Med. 128 (9): 950–5. doi:10.1016/j.amjmed.2015.02.017. PMID 25837517.
  44. Hoofien A, Yarden-Bilavski H, Ashkenazi S, Chodick G, Livni G (2018). "Leukemoid reaction in the pediatric population: etiologies, outcome, and implications". Eur J Pediatr. 177 (7): 1029–1036. doi:10.1007/s00431-018-3155-5. PMID 29696475.
  45. 45.0 45.1 45.2 Ellison TA, Mandal K (2018). "Leukemoid reaction: Case report". J Thorac Cardiovasc Surg. 155 (4): e117–e118. doi:10.1016/j.jtcvs.2017.08.125. PMID 29366572.
  46. Wang Z, Cai Q, Li G, Jiang N, Niu Y (2017). "Giant Pheochromocytoma With Leukemoid Reaction: A Case Report". Urology. 99: e17–e19. doi:10.1016/j.urology.2016.08.021. PMID 27720771.
  47. Agrawal D, Kurwale N, Sharma BS (2016). "Leukocytosis after routine cranial surgery: A potential marker for brain damage in intracranial surgery". Asian J Neurosurg. 11 (2): 109–13. doi:10.4103/1793-5482.145066. PMC 4802930. PMID 27057215.


Template:WikiDoc Sources