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Neutropenia Differential Diagnoses

  • Author: Christopher D Braden, DO; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Feb 26, 2016
 
 

Diagnostic Considerations

Other conditions to be considered include the following:

  • Large granular lymphocyte leukemia
  • Autoimmune diseases
  • Chronic myelomonocytic leukemia
  • Congenital neutropenia
  • Cyclic neutropenia
  • Drug-induced neutropenia
  • Large granular lymphocytic leukemia
  • Pseudoneutropenia

Obtain a detailed history in patients with neutropenia or agranulocytosis, with particular emphasis on medication use. The inquiry must extend back in time to include discontinued medications. Over-the-counter drugs must be included in the inquiry, because patients often do not consider these agents to be medications. Any possible occupational or accidental exposure to toxic chemicals or physical agents must be excluded. Agranulocytosis should be differentiated from other syndromes of bone-marrow failure, including pancytopenia and aplastic anemia. Leukemia should be excluded.

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital

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.

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.

References
  1. 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.

  2. 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.

  3. Schimpff SC. Empiric antibiotic therapy for granulocytopenic cancer patients. Am J Med. 1986 May 30. 80(5C):13-20. [Medline].

  4. 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. [Medline].

  5. [Guideline] Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15. 52(4):e56-93. [Medline]. [Full Text].

  6. Bodey GP. Managing infections in the immunocompromised patient. Clin Infect Dis. 2005 Apr 1. 40 Suppl 4:S239. [Medline].

  7. [Guideline] National Comprehensive Cancer Network. Prevention and Treatment of Cancer-Related Infections Version 2.2015. NCCN. Available at http://www.nccn.org/professionals/physician_gls/pdf/infections.pdf. Accessed: February 26, 2016.

  8. 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. [Medline].

  9. 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. [Medline].

  10. Finberg RW, Talcott JA. Fever and neutropenia--how to use a new treatment strategy. N Engl J Med. 1999 Jul 29. 341(5):362-3. [Medline].

  11. 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. [Medline].

  12. Mulcahy N. New ASCO Guideline on Neutropenia and Fever. Medscape Medical News. Jan 16 2013. Available at http://www.medscape.com/viewarticle/777736. Accessed: January 22, 2013.

  13. [Guideline] Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2013 Jan 14. [Medline].

  14. 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. [Medline].

  15. 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. [Medline].

  16. 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. [Medline].

  17. Mustafa MM, McClain KL. Diverse hematologic effects of parvovirus B19 infection. Pediatr Clin North Am. 1996 Jun. 43(3):809-21. [Medline].

  18. 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. [Medline]. [Full Text].

  19. 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. [Medline].

  20. Lee GR, Foerster J, Lukens J, et al, eds. Wintrobe’s Hematology. 10th ed. Baltimore, Md: William and Wilkins; 1999. 1836-88.

  21. Boxer LA. Immune neutropenias. Clinical and biological implications. Am J Pediatr Hematol Oncol. 1981 Spring. 3(1):89-96. [Medline].

  22. Welte K, Dale D. Pathophysiology and treatment of severe chronic neutropenia. Ann Hematol. 1996 Apr. 72(4):158-65. [Medline].

  23. Young NS. Agranulocytosis. JAMA. 1994 Mar 23-30. 271(12):935-8. [Medline].

  24. Berliner N, Horwitz M, Loughran TP Jr. Congenital and acquired neutropenia. Hematology Am Soc Hematol Educ Program. 2004. 63-79. [Medline].

  25. Sifton DW, Murray L, Kelly GL, Reilly S, eds. Physicians’ Desk Reference. 55th ed. Montvale, NJ: Medical Economics Company, Inc.; 2001. 551-6, 847-60, 1275-80, 1396-9, 1793-5, 1998-2002, 3068-71.

  26. American Society of Clinical Oncology. Recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J Clin Oncol. 1994 Nov. 12(11):2471-508. [Medline].

  27. Update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based clinical practice guidelines. American Society of Clinical Oncology. J Clin Oncol. 1996 Jun. 14(6):1957-60. [Medline].

  28. Vial T, Gallant C, Choqu-Kastylevsky G, Descotes J. Treatment of drug-induced agranulocytosis with haematopoietic growth factors: a review of the clinical experience. BioDrugs. 1999 Mar. 11(3):185-200. [Medline].

  29. D'Angelo G. Ethnic and genetic causes of neutropenia: clinical and therapeutic implications. Lab Hematol. 2009. 15(3):25-9. [Medline].

  30. 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. [Medline].

  31. 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. [Medline].

  32. Kelly S, Wheatley D. Prevention of febrile neutropenia: use of granulocyte colony-stimulating factors. Br J Cancer. 2009 Sep. 101 Suppl 1:S6-10. [Medline]. [Full Text].

  33. 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. [Medline].

  34. 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. [Medline]. [Full Text].

  35. Goulenok T, Fantin B. Antimicrobial Treatment of Febrile Neutropenia: Pharmacokinetic-Pharmacodynamic Considerations. Clin Pharmacokinet. 2013 Jun 27. [Medline].

  36. 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. [Medline].

  37. 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. [Medline].

  38. 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. [Medline].

  39. 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. [Medline].

  40. Cullen M, Baijal S. Prevention of febrile neutropenia: use of prophylactic antibiotics. Br J Cancer. 2009 Sep. 101 Suppl 1:S11-4. [Medline]. [Full Text].

  41. Krell D, Jones AL. Impact of effective prevention and management of febrile neutropenia. Br J Cancer. 2009 Sep. 101 Suppl 1:S23-6. [Medline]. [Full Text].

  42. 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. [Medline].

  43. 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. [Medline].

  44. 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. [Medline].

  45. 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. [Medline].

  46. MacVittie TJ. Therapy of radiation injury. Stem Cells. 1997. 15 Suppl 2:263-8. [Medline].

  47. 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. [Medline].

  48. [Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology, Myeloid Growth Factors v 1.2015. Available at http://www.nccn.org/professionals/physician_gls/PDF/myeloid_growth.pdf. Accessed: February 24, 2016.

  49. [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. [Medline].

  50. 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. [Medline].

  51. 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. [Medline].

  52. Dranitsaris G, Rayson D, Vincent M, Chang J, Gelmon K, Sandor D, et al. Identifying patients at high risk for neutropenic complications during chemotherapy for metastatic breast cancer with doxorubicin or pegylated liposomal doxorubicin: the development of a prediction model. Am J Clin Oncol. 2008 Aug. 31(4):369-74. [Medline].

  53. Walsh TJ, Finberg RW, Arndt C, Hiemenz J, Schwartz C, Bodensteiner D, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med. 1999 Mar 11. 340(10):764-71. [Medline].

  54. Curnutte J, Coates T. Disorder of phagocyte function and number. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000. 720-62.

  55. Douglas D. Antifungals cut risk of invasive infections in neutropenic patients. Reuters Health Information. September 9, 2013. [Full Text].

  56. Pechlivanoglou P, Le HH, Daenen S, Snowden JA, Postma MJ. Mixed treatment comparison of prophylaxis against invasive fungal infections in neutropenic patients receiving therapy for haematological malignancies: a systematic review. J Antimicrob Chemother. 2013 Aug 23. [Medline].

  57. Chustecka Z. Biosimilar Filgrastim Recommended for Approval in US. Medscape Medical News. January 7, 2015. Available at http://www.medscape.com/viewarticle/837725.

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Bilateral interstitial infiltrates in a 31-year-old patient with influenza pneumonia.
Anteroposterior chest radiograph in a young ED patient presenting with cough and malaise. The radiograph shows a classic posterior segment right upper lobe density consistent with active tuberculosis. This woman was admitted to isolation and started empirically on a 4-drug regimen in the ED. Tuberculosis was confirmed on sputum testing. Image courtesy of Remote Medicine, remotemedicine.org.
Lateral chest radiograph in a 31-year-old patient with influenza pneumonia. Image courtesy of Remote Medicine, remotemedicine.org.
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.
Table 1. Genetic (Hereditary) Conditions in Agranulocytosis[24]
SyndromeInheritanceGeneClinical Features
Cyclic neutropeniaAutosomal dominantELA2Alternate 21-day cycling of neutrophils and monocytes
Kostmann syndromeAutosomal recessiveUnknownStable neutropenia, no MDS or AML
Severe congenital neutropeniaAutosomal dominantELA2 (35-84%)Stable neutropenia, MDS or AML
Autosomal dominantGFI1Stable neutropenia, circulating myeloid progenitors, lymphopenia
Sex linkedWaspNeutropenic variant of Wiskott-Aldrich syndrome
Autosomal dominantG-CSFRG-CSF–refractory neutropenia, no AML or MDS
Hermansky-Pudlak syndrome type 2Autosomal recessiveAP3B1Severe congenital neutropenia, platelet dense-body defect, oculocutaneous albinism
Chediak-Higashi syndromeAutosomal recessiveLYSTNeutropenia, oculocutaneous albinism, giant lysosomes, impaired platelet function
Barth syndromeSex linkedTAZNeutropenia, often cyclic; cardiomyopathy, methylglutaconic aciduria
Cohen syndromeAutosomal recessiveCOH1Neutropenia, mental retardation, dysmorphism
Source: Modified from Berliner et al, 2004.[24]



AML = acute myeloid leukemia; G-CSF = granulocyte colony-stimulating factor; MDS = myelodysplastic syndrome.



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