Leukemoid reaction: Difference between revisions

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** [[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>.
** [[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>.
** [[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.
** [[Eosinophilic]] reactions develop in [[Allergy|allergic]] processes or in diseases with [[Allergy|allergies]], as well as in [[Parasitism|parasitic]] diseases. They are characterized by the development of a great number of [[eosinophils]], about 90% of leukocytes.
* Lymphomonocytic leukemoid reactions develop in [[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>.
* 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>.
* Lymphocytic leukemoid reactions develop in acute viral and bacterial infections and are characterized by [[leukocytosis]] with absolute [[lymphocytosis]].
* Lymphocytic leukemoid reactions develop in acute viral and bacterial infections and are characterized by [[leukocytosis]] with absolute [[lymphocytosis]].
* Plasmocytic leukemoid reactions occur in diseases caused by [[protozoa]] ([[toxoplasmosis]]), [[Virus|viral infections]] ([[chickenpox]], [[measles]], [[rubella]]). Increased level of plasma cells (2%) in [[splenomegaly]], [[blood]] and [[bone marrow]].
* Plasmocytic leukemoid reactions occur in diseases caused by [[protozoa]] ([[toxoplasmosis]]), [[Virus|viral infections]] ([[chickenpox]], [[measles]], [[rubella]]). Increased level of plasma cells (2%) in [[splenomegaly]], [[blood]] and [[bone marrow]].
* Leukemoid reactions with blast cells develop in severe viral infections ([[cytomegalovirus]], etc.). Blast transformation of [[B cell|B-lymphocytes]] may be observed in the bone marrow, lymph nodes and peripheral blood.
* Leukemoid reactions with blast cells develop in severe viral infections ([[cytomegalovirus]], etc.). Blast transformation of [[B cell|B-lymphocytes]] may be observed in the [[bone marrow]], [[Lymph node|lymph nodes]], and peripheral blood.
* Secondary absolute [[Polycythemia|erythrocytosis]] is caused by increased [[erythropoiesis]], relative hemoconcentration and [[polycythemia]]. It is characterized by increased red blood cell count.
* Secondary absolute [[Polycythemia|erythrocytosis]] is caused by increased [[erythropoiesis]], relative hemoconcentration and [[polycythemia]]. It is characterized by increased [[red blood cell]] count.
* Secondary [[thrombocytosis]] is possible in [[malignant]] tumors, [[Inflammation|inflammatory diseases]], following [[bleeding]], [[Hemolysis|hemolytic]] crises, after surgical operations and [[splenectomy]].
* Secondary [[thrombocytosis]] is possible in [[malignant]] tumors, [[Inflammation|inflammatory diseases]], following [[bleeding]], [[Hemolysis|hemolytic]] crises, after surgical operations and [[splenectomy]].


==Causes==
==Causes==
* Neutrophilic leukemoid reactions <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>:
* 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]], [[abscess]], [[diphtheria]], [[Pneumonia|lobar pneumonia]], [[tuberculosis]], [[dysentery]]
** [[Infection|Infections]] - [[sepsis]], [[scarlet fever]], [[abscess]], [[diphtheria]], [[Pneumonia|lobar pneumonia]], [[tuberculosis]], [[dysentery]]
** Exposure to ionizing [[Radiation therapy|radiation]].
** Exposure to ionizing [[Radiation therapy|radiation]].
** Injuries of the skull.
** Injuries of the skull.
** Intoxication ([[Chronic renal failure pathophysiology|uremia]], CO poisoning).
** Intoxication ([[Chronic renal failure pathophysiology|uremia]], CO-poisoning).
** Bone marrow metastases of malignant tumors - [[Lymphogranulomatosis X T-cell lymphoma|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 [[Allergy|allergies]], as well as in [[Parasitism|parasitic]] diseases.  
** Allergic processes or in diseases with [[Allergy|allergies]], as well as in [[Parasitism|parasitic]] diseases.  
* Lymphomonocytic leukemoid reactions:  
* Lymphomonocytic leukemoid reactions:  
Line 86: Line 86:
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>:
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
|+ Leukemia vs leukemoid reaction
! Differentiating features !! Leukemia !! Leukemoid reaction
! Differentiating features !! Leukemia !! Leukemoid reaction

Revision as of 21:09, 5 November 2018

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

Overview

Leukemoid reaction is a reversible increase in production of white blood cells in response to a stimulus, with white blood cell count of more than 25000-30000 per mm3 . Leukocytosis is increase in white blood cell count of more than 10,000 per mm3 and when the count exceeds 25000, with more than 2% immature white blood cells but absence of any blast cells, differentiating it from leukemias. Leukemoid reaction is classified according to the type of hematopoietic lineage of the bone marrow. Leukemoid reactions are mostly triggered by bacterial or viral infections. Leukemoid reaction is differentiated from leukemias by the absence of blast cells on peripheral blood film and high LAP score. Leukemoid reaction can lead to serious complications such as tumor lysis syndrome and DIC. The treatment includes treating the underlying cause and leukapheresis.

Historical Perspective

  • Leukemoid reaction was discovered in 1926 by Krumbharr.

Classification

Leukemoid reaction can be classified according to the type of hematopoietic lineage of the bone marrow[1].

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]:

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

products of tissue destruction

Pathogenesis The transformation of normal haematopoietic

cells to a tumor

Activation of normal hematopoiesis and exit of immature leukocytes

into the bloodstream.

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

Epidemiology and Demographics

Age

  • Patients of all age groups may develop leukemoid reaction[1][13].
  • Normal white blood count differential changes with age.
  • Leukemoid reaction in neonates is more common, compared to children and adults.

Gender

  • Leukemoid reaction affects men and women equally.

Race

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

Risk Factors

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

Screening

No screening is done for leukemoid reaction.

Natural History, Complications, and Prognosis

History

Complications

Prognosis

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

Diagnosis

Symptoms

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

Laboratory findings

Electrocardiogram

No specific ECG changes in leukemoid reaction.

X-Ray

No specific x ray changes in leukemoid reaction.

Echocardiograph and Ultrasound

No echocardiography and ultrasound findings.

CT

No CT scan findings in leukemoid reaction.

MRI

No specific MRI findings in leukemoid reaction.

Treatment

Medical Therapy

Surgery

The treatment depends on the underlying cause.

Primary prevention

Prevention and treatment of infections.

Secondary prevention

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

See also

References

  1. 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. 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.
  14. 14.0 14.1 14.2 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.
  15. 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.
  16. 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.


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