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 bacteriaDefinition of neutropenia:NORMAL: WBC 4400-11000 cells/microL; neutrophils make up 40-70% of thatNeutropenia defined by ANC: WBC (cells/microL) x percent (PMNs  +  bands) ÷ 100 Breakdown:Neutropenia: ANC <1500 cells/microLMild: ANC ≥1000 and <1500 cells/microLModerate: ANC ≥500 and <1000 cells/microLSevere: ANC <500 cells/microLAgranulocytosis: ANC <200 cells/microLApproach to workup: HISTORY IS KEY!Medications; examples of common culprits-  Chemotherapy Methimazole Clozapine InfectionsAny infections due to bone marrow suppression Toxins Less common causes: CongenitalSevere congenital neutropenia:Diagnosed in childhood; used to be fatal, but now patients living longer because of G-CSF support10-30% risk of AML in lifetimeMutations in neutrophil elastase (ELANE) gene or mitochondrial HAX1 gene Cyclic neutropenia:Self-limiting neutropenia that occurs every 2-5 weeksSpectrum of symptoms: none or oral ulcers/mild infectionsConstitutional/ethnic neutropenia:Mild neutropenia (ANC >1000)No history of infectionsMore common in people of Mediterranean and African descentDuffy Antigen Receptor Complex (DARC) gene mutations in patients of African originBenign Familial:Mild neutropeniaNot linked to particular ethnic groupUnclear underlying etiologyAutoimmunePrimary autoimmune neutropenia rare in adultsTypically secondary autoimmune neutropeniaDue to underlying autoimmune disorderSeen with SLE and can worsen with flare of diseaseTypically mild, seldom needs treatment unless ANC <500Felty syndrome:  Rheumatoid arthritis, splenomegaly, and neutropeniaNeutropenia improves with treatment of RA MalignancyLarge granular lymphocyte (LGL) leukemia:Often associated with RA and shares features of Felty syndrome (RA, splenomegaly)Caused by monoclonal population of large granular lymphocytesIn contrast, in Felty’s: polyclonal or oligoclonalT-cell LGL is more commonly associated with neutropeniaRequires treatment with methotrexate or cyclophosphamideDietaryB12 and folate rarely cause isolated neutropeniaCopper deficiency (gastric bypass): Zinc excess can cause copper deficiencies – ask about denture creams in your history!  Workup:History:Prior CBCsHistory of recurrent infections (pneumonia, sinusitis, skin/soft tissue, dental caries)Ethnic backgroundFamily historySocial historyDietary historySurgical history (gastric bypass)Physical exam:AdenopathySplenomegalySkin findings suggesting recent ulcersAphthous ulcersexample: https://en.wikipedia.org/wiki/Aphthous_stomatitisTesting:CBC with differentialCMP – assess liver and renal function Peripheral smearHIV, Hepatitis serologiesSpecial scenariosANA – if autoimmune disease expectedRF – if autoimmune disease expectedESR – if autoimmune disease expected; probably not great for inpatient workupCRP – if autoimmune disease expected; probably not great for inpatient workupFlow cytometry for LGLBone marrow biopsy – mainly for unexplained neutropenia to rule out neoplastic process, such as leukemia, lymphoma, myeloma; if longstanding, likely negativeManagement:Treat the underlying causeAutoimmune neutropenia –When to suspect? Workup is negative, but their counts still continue to worsenTreatment if they have serious complicationsTreat with rituximabLGL-Responds to low dose methotrexate or cyclophosphamideDo you give G-CSF?For patients with recurrent/severe infections or mucosal erosionsDo not treat based on the number aloneTakes time for the growth factors to workReferences: 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 (TheFellowO