Jacobson CA, Berliner N. Neutropenia. Greer JP, Arber DA, Glader B, et al, eds. Wintrobe’s Clinical Hematology. 13th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2014. 1279-89.
Smith CW. Production, Distribution, and Fate of Neutrophils. Kaushansky K, Lichtman MA, Prchal JT, et al. Williams Hematology. 9th ed. New York, NY: McGraw-Hill; 2016.
Justiz Vaillant AA, Zito PM. Neutropenia. 2023 Jan. [QxMD MEDLINE Link]. [Full Text].
Schwarzinger M, Sagaon-Teyssier L, Cabaret O, Bretagne S, Cordonnier C, Pautas C, et al. Performance of serum biomarkers for the early detection of invasive aspergillosis in febrile, neutropenic patients: a multi-state model. PLoS One. 2013. 8(6):e65776. [QxMD MEDLINE Link].
[Guideline] Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, et al. Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin Oncol. 2018 May 10. 36 (14):1443-1453. [QxMD MEDLINE Link]. [Full Text].
Bodey GP. Managing infections in the immunocompromised patient. Clin Infect Dis. 2005 Apr 1. 40 Suppl 4:S239. [QxMD MEDLINE Link].
[Guideline] National Comprehensive Cancer Network. Prevention and Treatment of Cancer-Related Infections. NCCN. Available at http://www.nccn.org/professionals/physician_gls/pdf/infections.pdf. Version 2.2020 — June 5, 2020; Accessed: March 25, 2021.
Kern WV, Cometta A, De Bock R, Langenaeken J, Paesmans M, Gaya H. Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med. 1999 Jul 29. 341(5):312-8. [QxMD MEDLINE Link].
Bow EJ, Mandell LA, Louie TJ, Feld R, Palmer M, Zee B, et al. Quinolone-based antibacterial chemoprophylaxis in neutropenic patients: effect of augmented gram-positive activity on infectious morbidity. National Cancer Institute of Canada Clinical Trials Group. Ann Intern Med. 1996 Aug 1. 125(3):183-90. [QxMD MEDLINE Link].
Freifeld A, Marchigiani D, Walsh T, Chanock S, Lewis L, Hiemenz J, et al. A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy. N Engl J Med. 1999 Jul 29. 341(5):305-11. [QxMD MEDLINE Link].
[Guideline] Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, et al. Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. J Clin Oncol. 2018 Sep 4. JCO1800374. [QxMD MEDLINE Link]. [Full Text].
Formiga F, Mitjavila F, Pac M, Moga I. Effective splenectomy in agranulocytosis associated with systemic lupus erythematosus. J Rheumatol. 1997 Jan. 24(1):234-5. [QxMD MEDLINE Link].
Liew PX, Kubes P. The Neutrophil's Role During Health and Disease. Physiol Rev. 2019 Apr 1. 99 (2):1223-1248. [QxMD MEDLINE Link]. [Full Text].
Palmblad J, Nilsson CC, Höglund P, Papadaki HA. How we diagnose and treat neutropenia in adults. Expert Rev Hematol. 2016 Feb 16. Vol 2:1-9. [QxMD MEDLINE Link].
Haddy TB, Rana SR, Castro O. Benign ethnic neutropenia: what is a normal absolute neutrophil count?. J Lab Clin Med. 1999 Jan. 133(1):15-22. [QxMD MEDLINE Link].
Mustafa MM, McClain KL. Diverse hematologic effects of parvovirus B19 infection. Pediatr Clin North Am. 1996 Jun. 43(3):809-21. [QxMD MEDLINE Link].
Rodriguez A, Yood RA, Condon TJ, Foster CS. Recurrent uveitis in a patient with adult onset cyclic neutropenia associated with increased large granular lymphocytes. Br J Ophthalmol. 1997 May. 81(5):415. [QxMD MEDLINE Link]. [Full Text].
Bar-Joseph G, Halberthal M, Sweed Y, Bialik V, Shoshani O, Etzioni A. Clostridium septicum infection in children with cyclic neutropenia. J Pediatr. 1997 Aug. 131(2):317-9. [QxMD MEDLINE Link].
Tak T, Tesselaar K, Pillay J, Borghans JA, Koenderman L. What's your age again? Determination of human neutrophil half-lives revisited. J Leukoc Biol. 2013 Oct. 94 (4):595-601. [QxMD MEDLINE Link].
Boxer LA. Immune neutropenias. Clinical and biological implications. Am J Pediatr Hematol Oncol. 1981 Spring. 3(1):89-96. [QxMD MEDLINE Link].
Welte K, Dale D. Pathophysiology and treatment of severe chronic neutropenia. Ann Hematol. 1996 Apr. 72(4):158-65. [QxMD MEDLINE Link].
Young NS. Agranulocytosis. JAMA. 1994 Mar 23-30. 271(12):935-8. [QxMD MEDLINE Link].
Berliner N, Horwitz M, Loughran TP Jr. Congenital and acquired neutropenia. Hematology Am Soc Hematol Educ Program. 2004. 63-79. [QxMD MEDLINE Link].
D'Angelo G. Ethnic and genetic causes of neutropenia: clinical and therapeutic implications. Lab Hematol. 2009. 15(3):25-9. [QxMD MEDLINE Link].
Bohlius J, Herbst C, Reiser M, Schwarzer G, Engert A. Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma. Cochrane Database Syst Rev. 2008 Oct 8. CD003189. [QxMD MEDLINE Link].
D'Souza A, Jaiyesimi I, Trainor L, Venuturumili P. Granulocyte colony-stimulating factor administration: adverse events. Transfus Med Rev. 2008 Oct. 22(4):280-90. [QxMD MEDLINE Link].
Kelly S, Wheatley D. Prevention of febrile neutropenia: use of granulocyte colony-stimulating factors. Br J Cancer. 2009 Sep. 101 Suppl 1:S6-10. [QxMD MEDLINE Link]. [Full Text].
Carlsson G, Aprikyan AA, Ericson KG, Stein S, Makaryan V, Dale DC, et al. Neutrophil elastase and granulocyte colony-stimulating factor receptor mutation analyses and leukemia evolution in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. Haematologica. 2006 May. 91(5):589-95. [QxMD MEDLINE Link].
Atallah-Yunes SA, Ready A, Newburger PE. Benign ethnic neutropenia. Blood Rev. 2019 Sep. 37:100586. [QxMD MEDLINE Link]. [Full Text].
Xia J, Bolyard AA, Rodger E, Stein S, Aprikyan AA, Dale DC, et al. Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia. Br J Haematol. 2009 Nov. 147(4):535-42. [QxMD MEDLINE Link]. [Full Text].
Heusinkveld LE, Majumdar S, Gao JL, McDermott DH, Murphy PM. WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure. J Clin Immunol. 2019 Aug. 39 (6):532-556. [QxMD MEDLINE Link]. [Full Text].
Goulenok T, Fantin B. Antimicrobial Treatment of Febrile Neutropenia: Pharmacokinetic-Pharmacodynamic Considerations. Clin Pharmacokinet. 2013 Jun 27. [QxMD MEDLINE Link].
Andersen CL, Tesfa D, Siersma VD, Sandholdt H, Hasselbalch H, Bjerrum OW, et al. Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study. J Intern Med. 2016 Jan 21. [QxMD MEDLINE Link].
Mueller EL, Croop J, Carroll AE. Fever and neutropenia hospital discharges in children with cancer: A 2012 update. Pediatr Hematol Oncol. 2016 Feb 22. 1-10. [QxMD MEDLINE Link].
Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007 Apr 3. 146(7):486-92. [QxMD MEDLINE Link].
Grann VR, Bowman N, Joseph C, Wei Y, Horwitz MS, Jacobson JS, et al. Neutropenia in 6 ethnic groups from the Caribbean and the U.S. Cancer. 2008 Aug 15. 113(4):854-60. [QxMD MEDLINE Link].
Cullen M, Baijal S. Prevention of febrile neutropenia: use of prophylactic antibiotics. Br J Cancer. 2009 Sep. 101 Suppl 1:S11-4. [QxMD MEDLINE Link]. [Full Text].
Krell D, Jones AL. Impact of effective prevention and management of febrile neutropenia. Br J Cancer. 2009 Sep. 101 Suppl 1:S23-6. [QxMD MEDLINE Link]. [Full Text].
Pathak R, Giri S, Aryal MR, Karmacharya P, Bhatt VR, Martin MG. Mortality, length of stay, and health care costs of febrile neutropenia-related hospitalizations among patients with breast cancer in the United States. Support Care Cancer. 2015 Jan 4. [QxMD MEDLINE Link].
Meisel A, von Felten S, Vogt DR, Liewen H, de Wit R, de Bono J, et al. Severe neutropenia during cabazitaxel treatment is associated with survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of the TROPIC phase III trial. Eur J Cancer. 2016 Jan 29. 56:93-100. [QxMD MEDLINE Link].
Jansen RR, Biemond BJ, Schinkel J, Koekkoek SM, Molenkamp R, de Jong MD, et al. Febrile neutropenia: significance of elaborated screening for respiratory viruses, and the comparison of different sampling methods, in neutropenic patients with hematological malignancies. Virol J. 2013 Jun 27. 10(1):212. [QxMD MEDLINE Link].
Hellmich B, Schnabel A, Gross WL. Treatment of severe neutropenia due to Felty's syndrome or systemic lupus erythematosus with granulocyte colony-stimulating factor. Semin Arthritis Rheum. 1999 Oct. 29(2):82-99. [QxMD MEDLINE Link].
MacVittie TJ. Therapy of radiation injury. Stem Cells. 1997. 15 Suppl 2:263-8. [QxMD MEDLINE Link].
Mac Manus M, Lamborn K, Khan W, Varghese A, Graef L, Knox S. Radiotherapy-associated neutropenia and thrombocytopenia: analysis of risk factors and development of a predictive model. Blood. 1997 Apr 1. 89(7):2303-10. [QxMD MEDLINE Link].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology, Hematopoietic Growth Factors. Available at https://www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf. Version 1.2024 — October 19, 2023; Accessed: November 21, 2023.
[Guideline] Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015 Oct 1. 33 (28):3199-212. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011 Jan. 47 (1):8-32. [QxMD MEDLINE Link].
Wang XJ, Tang T, Farid M, Quek R, Tao M, Lim ST, et al. Routine Primary Prophylaxis for Febrile Neutropenia with Biosimilar Granulocyte Colony-Stimulating Factor (Nivestim) or Pegfilgrastim Is Cost Effective in Non-Hodgkin Lymphoma Patients undergoing Curative-Intent R-CHOP Chemotherapy. PLoS One. 2016. 11 (2):e0148901. [QxMD MEDLINE Link].
Massey E, Paulus U, Doree C, Stanworth S. Granulocyte transfusions for preventing infections in patients with neutropenia or neutrophil dysfunction. Cochrane Database Syst Rev. 2009 Jan 21. CD005341. [QxMD MEDLINE Link].

Media Gallery

The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18-kg (7-lb) spleen crosses the midline. Inferiorly, it extends into the pelvis.
Doppler sonogram at the splenic hilum reveals hepatofugal venous flow in a patient with portal hypertension.
Two neutrophils among red blood cells. Courtesy of Britannica (https://www.britannica.com/science/neutrophil).

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Table 1. Genetic (Hereditary) Conditions in Neutropenia

Table 1. Genetic (Hereditary) Conditions in Neutropenia

Syndrome	Inheritance	Gene	Clinical Features
Cyclic neutropenia	Autosomal dominant	ELA2	Alternate 21-day cycling of neutrophils and monocytes
Kostmann syndrome	Autosomal recessive	Unknown	Stable neutropenia, no MDS or AML
Severe congenital neutropenia	Autosomal dominant	ELA2 (35-84%)	Stable neutropenia, MDS or AML
	Autosomal dominant	GFI1	Stable neutropenia, circulating myeloid progenitors, lymphopenia
	Sex linked	Wasp	Neutropenic variant of Wiskott-Aldrich syndrome
	Autosomal dominant	G-CSFR	G-CSF–refractory neutropenia, no AML or MDS
Hermansky-Pudlak syndrome type 2	Autosomal recessive	AP3B1	Severe congenital neutropenia, platelet dense-body defect, oculocutaneous albinism
Chediak-Higashi syndrome	Autosomal recessive	LYST	Neutropenia, oculocutaneous albinism, giant lysosomes, impaired platelet function
Barth syndrome	Sex linked	TAZ	Neutropenia, often cyclic; cardiomyopathy, methylglutaconic aciduria
Cohen syndrome	Autosomal recessive	COH1	Neutropenia, mental retardation, dysmorphism
Thrombocytopenia with absent radii (TAR)	Autosomal recessive	RBM8A	Thrombocytopenia, MDS, absent radii, abnormal ulna
Diamond-Blackfan anemia	Autosomal dominant, X-linked recessive	RPS19, RPL5, RPS26	Macrocytic anemia, other cytopenias, solid tumors, short stature, abnormal thumbs, cardiac septal defect
Fanconi syndrome	Autosomal recessive (rarely, X-linked recessive or autosomal dominant)	FANCA, FANCC, FANCG	Pancytopenia, solid tumors, skin hyperpigmentation and café au lait spots, abnormal thumbs
Dyskeratosis congenita	X-linked recessive, autosomal dominant, autosomal recessive	DKC1, TINF2	Pancytopenia, MDS, nail dystrophy, leukoplakia, solid tumors
Source: Modified from Berliner et al, 2004.^[23] AML = acute myeloid leukemia; G-CSF = granulocyte colony-stimulating factor; MDS = myelodysplastic syndrome.

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Author

Carly DeFaria, MD Resident Physician, Department of Internal Medicine, Einstein Medical Center

Carly DeFaria, MD is a member of the following medical societies: American College of Physicians, American Medical Student Association/Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Claudia M da Costa Dourado, MD Clinical Assistant Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Program Director, Hematology and Medical Oncology Fellowship Program, Attending Physician, Division of Hematology and Medical Oncology, Department of Medicine, Einstein Medical Center Philadelphia

Claudia M da Costa Dourado, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital; Medical Director, Deaconess Hospital Outpatient Infusion Centers; Chairman, Deaconess Hospital Cancer Committee

Christopher D Braden, DO is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Acknowledgements

Ariel Distenfeld, MD Clinical Professor, Department of Medicine, New York University School of Medicine

Disclosure: Nothing to disclose.

John E Godwin, MD, MS Professor of Medicine, Chief Division of Hematology/Oncology, Associate Director, Simmons Cooper Cancer Institute, Southern Illinois University School of Medicine

John E Godwin, MD, MS is a member of the following medical societies: American Association for the Advancement of Science, American Heart Association, and American Society of Hematology

Disclosure: Nothing to disclose.

Kush Sachdeva, MD Southern Oncology and Hematology Associates, South Jersey Healthcare, Fox Chase Cancer Center Partner

Disclosure: Nothing to disclose.

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