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Absolute neutrophil count ( ANC ) < 1.5 x 109 May suggest an underlying systemic or haematological disorder Increased risk of infections
Common incidental finding in primary care – often ○ drug induced ○ acute viral infection Agranulocytosis usually used to describe a more severe subset of neutropenia – count less than 0.2 Carries risk of severe life threatening infections with susceptibility to opportunistic organisms Risk of infection is more severe when neutropenia is due to impaired production from chemotherapy or marrow failure Persons of African descent often have lower than normal neutrophil count
Decreased or ineffective production Accelerated turnover in blood Dislocation of shifts of cells from circulating to the marginal blood pools Unclear or combination of more than one mechanism ( eg thyroid dysfunction) .Rare for primary haematological malignancy to present with isolated neutropenia ( other cell lines are usually also affected )
Transient- Commonly associated with viral infections Eg EBV causing infectious mononucleosis is a very common cause ( see below ) Overwhelming bacterial infection can also deplete bone marrow reserves Chemotherapy agents Inflammatory and autoimmune conditions Drugs ( see below )
chronic- Less than 1.5 lasting > 3 months Can be a normal variant with people in good health- periodic FBC testing may indicate if ○ any other haematological abnormality present ○ evidence underlying infection ○ inflammatory or malignant disease A count of < 0.5 – warrants an indepth evaluation Important to consider the condition when the sample was obtained ( count may vary considerably over short period of time , activity , exercise , eating etc ) ○ take several measurements
Generally regarded as presence of a fever > 38° with an absolute neutrophil count of < 1.0 x 109
Result of bone marrow suppression- common SE of chemotherapy Risk of life threatening infections Most common complication of cancer chemotherapy Risk infection -consider in any systemically unwell patient receiving chemotherapy even if no fever present Risk increases with ○ age ○ advanced stage of disease ○ comorbidities ○ haematological malignancy ○ previous episode of febrile neutropenia ○ combined chemo-radiotherapy ○ poor nutritional status ○ Female ○ Hb < 12 ○ open wound or active infections Cases continue to be missed on initial presentation ○ not considered ○ patient may not disclose ○ lack of access to medical records ○ inability to mount an adequate inflammatory response – ie signs and symptoms may be minimal ( providing false reassurance ) Detailed history ○ nature of chemotherapy , which cancer ○ timing may give guidance on risk- although often unpredictable and should not be relied on ○ prior prophylactic antibiotics ○ concomitant steroid use ( suppressed inflammatory response ) ○ recent surgery Haematological malignancies can cause myelosuppression in patient even without chemotherapy
Presentation can be vague or with minimal symptoms ○ feeling hot or cold ○ rigors ○ sweats ○ flu like illness ○ general malaise Check for sore mouth and diarrhoea ( mucositis ) Do not wait for result of an urgent FBC – patients may decompensate rapidly Aim to determine how unwell the patient is Temp Signs of shock Focus of infection ( often not apparent ) If central line- check for signs of infection refer immediately- patients should receive IV antibiotics within 60 mins
Medical and family history ( heritable defects ) H/O recurrent infections Ask about oral inflammations ○ mouth ulcers ○ gingivitis ○ periodontitis ○ tooth loss , replacement Recurrent sinusitis and otitis Symptoms of pneumonia Perirectal pain and irritation
R/O Infection and Drug related causes Blood film Further tests- decide on individual basis Chronic viral serology Antinuclear antibodies and Rheumatoid factor Serum Immunoglobulin ( Ig)Antineutrohil antibodies B12 , Folate , Iron , Ferritin TFT , LFT , HIV – if risk factors presentUs&Es if drug related -usually mild. -moderate decide on basis of risks/ benefit of treatment whether to continue the drug or not.- if continued monitor carefully Severe cases of drug related neutropenia ie < 0.1 discontinue the drug
Suggestion of progressive or serious disease of any kind Bone marrow disorder suspected ○ eg anaemia and thrombocytopenia develops with pre-existing neutropenia Severe neutropenia with a downward trend in absolute neutrophil count Consistent neutropenia < 1.0
LINKS AND RESOURCES
PATIENT INFORMATION
A complete resource for the patient from Lymphoma action https://lymphoma-action.org.uk/about-lymphoma-side-effects-treatment/neutropenia
Cancer Net on neutropenia https://www.cancer.net/coping-with-cancer/physical-emotional-and-social-effects-cancer/managing-physical-side-effects/neutropenia
CDC printable 2 page leaflet warning for chemotherapy patients https://www.cdc.gov/cancer/preventinfections/pdf/neutropenia.pdf
BC Cancer care page with a printable link on neutropenia http://www.bccancer.bc.ca/health-info/coping-with-cancer/managing-symptoms-side-effects/neutropenia
Understanding severe chronic neutropenia a 28 page document by Severe Chronic Neutropenia International Registry for patients – a good read for any clinician as well https://depts.washington.edu/registry/Patient_Handbook_2013.pdf
Chronic neutropenia PIL from Indiana Hemophilia & Thrombosis Center https://www.ihtc.org/chronic-neutropenia/
INFORMATION FOR CLINICIANS
NICE guideline -Neutropenic sepsis:
prevention and management of neutropenic sepsis in cancer patients https://www.nice.org.uk/guidance/cg151
ESMO clinical practice guideline on febrile neutropenia https://www.esmo.org/guidelines/supportive-and-palliative-care/febrile-neutropaenia
Suspected Neutropenic Sepsis guideline from Wrightington, Wigan and Leight NHS Foundation Trust https://www.wwl.nhs.uk/Library/FOI/Requests/2012_2013/July_2013/1316_TW11-026_SOP2_Suspected_Neutropenia_Sepsis_Fast_Track_Pathway_Feb2013.pdf
Open access BMJ article Chasing the Golden Hour – Lessons learned from improving initial neutropenic sepsis management.
Benign Ethnic Neutropenia ( abstract ) https://www.sciencedirect.com/science/article/abs/pii/S0268960X19300244#ab0005
Further reading on isolated chronic neutropenia Gupta A, Dhingra A. Incidental Chronic Neutropenia in an Asymptomatic Adult. Cureus. 2017;9(10):e1779. Published 2017 Oct 17. doi:10.7759/cureus.1779 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732009/
A comprehensive article ” Evaluation and Management of Patients with Isolated Neutropenia “ Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. Semin Hematol. 2013;50(3):198–206. doi:10.1053/j.seminhematol.2013.06.010 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748385/
References
- Newburger, Peter E, and David C Dale. “Evaluation and management of patients with isolated neutropenia.” Seminars in hematology vol. 50,3 (2013): 198-206. doi:10.1053/j.seminhematol.2013.06.010 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748385/
- Neutropenia in primary care BMJ 2014 ;349:g5340
- Febrile neutropenia BMJ 2010 ;341 ; c6981
- Neutropenia Medscape Christopher D Braden et al Updated Aug 2017
- van Staa, T., Boulton, F., Cooper, C., Hagenbeek, A., Inskip, H. and Leufkens, H. (2003), Neutropenia and agranulocytosis in England and Wales: Incidence and risk factors. Am. J. Hematol., 72: 248-254. doi:10.1002/ajh.1029572:248 -254 ( 2003 )
- How We Evaluate and Treat Neutropenia in Adults : Outpatient Evaluation of Nuetropenia Medscape CME
- Lima, C.S.P., Paula, E.V., Takahashi, T. et al. Causes of incidental neutropenia in adulthood. Ann Hematol 85, 705–709 (2006). https://doi.org/10.1007/s00277-006-0150-0) https://link.springer.com/article/10.1007/s00277-006-0150-0#citeas
- Essential Haematology-A. V Hoffbrand , P.A.H. Moss
- Oxford Handbook of Haematology – Reduced WBC Count
- Management of febrile neutropenia: ESMO Clinical Practice Guidelines de Naurois, J. et al. Annals of Oncology, Volume 21, v252 – v256 https://www.annalsofoncology.org/article/S0923-7534(19)39644-9/fulltext
- Neutropenic Sepsis Prevention and Management of Neutropenic Sepsis in Cancer Patients st Velindre Cancer Centre Version 1.6 11.2014
- Neutropenic sepsis: prevention and management of neutropenic sepsis in
cancer patients September 2012
Developed for NICE by the National Collaborating Centre for Cancer https://www.nice.org.uk/guidance/cg151/evidence/full-guideline-pdf-188303581
