Episode 011: Cytopenias Series Pt. 3 - Neutropenia

In our final stop in our Cytopenias series, we discuss the ins and outs of neutropenia. This is another very commonly seen issue in the clinic and in the hospital so most definitely high yield! Why is neutropenia dangerous? Prone to infections, especially gut translocation of bacteria Definition of neutropenia: NORMAL: WBC 4400-11000 cells/microL; neutrophils make up 40-70% of that Neutropenia defined by ANC: WBC (cells/microL) x percent (PMNs + bands) ÷ 100 Breakdown: Neutropenia: ANC <1500 cells/microL Mild: ANC ≥1000 and <1500 cells/microL Moderate: ANC ≥500 and <1000 cells/microL Severe: ANC <500 cells/microL Agranulocytosis: ANC <200 cells/microL Approach to workup: HISTORY IS KEY! Medications; examples of common culprits- Chemotherapy Methimazole Clozapine Infections Any infections due to bone marrow suppression Toxins Less common causes: Congenital Severe congenital neutropenia: Diagnosed in childhood; used to be fatal, but now patients living longer because of G-CSF support 10-30% risk of AML in lifetime Mutations in neutrophil elastase (ELANE) gene or mitochondrial HAX1 gene Cyclic neutropenia: Self-limiting neutropenia that occurs every 2-5 weeks Spectrum of symptoms: none or oral ulcers/mild infections Constitutional/ethnic neutropenia: Mild neutropenia (ANC >1000) No history of infections More common in people of Mediterranean and African descent Duffy Antigen Receptor Complex (DARC) gene mutations in patients of African origin Benign Familial: Mild neutropenia Not linked to particular ethnic group Unclear underlying etiology Autoimmune Primary autoimmune neutropenia rare in adults Typically secondary autoimmune neutropenia Due to underlying autoimmune disorder Seen with SLE and can worsen with flare of disease Typically mild, seldom needs treatment unless ANC <500 Felty syndrome: Rheumatoid arthritis, splenomegaly, and neutropenia Neutropenia improves with treatment of RA Malignancy Large granular lymphocyte (LGL) leukemia: Often associated with RA and shares features of Felty syndrome (RA, splenomegaly) Caused by monoclonal population of large granular lymphocytes In contrast, in Felty’s: polyclonal or oligoclonal T-cell LGL is more commonly associated with neutropenia Requires treatment with methotrexate or cyclophosphamide Dietary B12 and folate rarely cause isolated neutropenia Copper deficiency (gastric bypass): Zinc excess can cause copper deficiencies – ask about denture creams in your history! Workup: History: Prior CBCs History of recurrent infections (pneumonia, sinusitis, skin/soft tissue, dental caries) Ethnic background Family history Social history Dietary history Surgical history (gastric bypass) Physical exam: Adenopathy Splenomegaly Skin findings suggesting recent ulcers Aphthous ulcers example: https://en.wikipedia.org/wiki/Aphthous_stomatitis Testing: CBC with differential CMP – assess liver and renal function Peripheral smear HIV, Hepatitis serologies Special scenarios ANA – if autoimmune disease expected RF – if autoimmune disease expected ESR – if autoimmune disease expected; probably not great for inpatient workup CRP – if autoimmune disease expected; probably not great for inpatient workup Flow cytometry for LGL Bone marrow biopsy – mainly for unexplained neutropenia to rule out neoplastic process, such as leukemia, lymphoma, myeloma; if longstanding, likely negative Management: Treat the underlying cause Autoimmune neutropenia – When to suspect? Workup is negative, but their counts still continue to worsen Treatment if they have serious complications Treat with rituximab LGL- Responds to low dose methotrexate or cyclophosphamide Do you give G-CSF? For patients with recurrent/severe infections or mucosal erosions Do not treat based on the number alone Takes time for the growth factors to work References: https://doi.org/10.1182/blood-2014-02-482612 - Great “How I Treat” article from Blood! https://www.uptodate.com/contents/approach-to-the-adult-with-unexplained-neutropenia - UpToDate article written by same author as Blood article Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCall Instagram: @TheFellowOnCall Listen in on: Apple Podcast, Spotify, and Google Podcast