Abstract
Isolated neutropenia without anemia or thrombocytopenia is a common clinical problem. The etiology of neutropenia may vary from transient bone marrow suppression, caused by self-limited viral illnesses, to previously undiagnosed congenital syndromes or serious systemic diseases. Consequently, determining the underlying cause of neutropenia and what treatment is required can be challenging. Acquired neutropenia is common and most of the times an etiologic factor can be found. Congenital neutropenia (CN) is rare, and we still have a lot to learn from mutational analysis as to the exact role of gene abnormalities in the pathogenesis of these complex diseases. This mini-review discusses a proposed approach to neutropenia in the adult patient.
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References
Boxer LA. How to approach neutropenia. Hematology Am Soc Hematol Educ Program 2012;2012;174–82.
Munshi HG, Montgomery RB. Severe neutropenia: a diagnostic approach. West J Med 2000;172;248–52.
Gibson C, Berliner N. How we evaluate and treat neutropenia in adults. Blood 2014;124;1251–8; quiz 1378.
Borregaard N, Boxer LA. Disorders of neutrophil function. In: Kauskhansky K, Lichtman MA, Beutler E, Kipps TJ, Seligshon U, Prchal JT, editors. Williams hematology, 8th Ed. New York, NY: McGraw-Hill; 2010, pp. 951–86.
Papadaki HA, Pontikoglou C. Pathophysiologic mechanisms, clinical features and treatment of idiopathic neutropenia. Expert Rev Hematol 2008;1;217–29.
Reich D, Nalls MA, Kao WHL, Akylbekova EL, Tandon A, Patterson N, et al. Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet 2009;5;e1000360.
Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 2013;98;1826–35.
Palmblad J, Dufour C, Papadaki HA. How we diagnose neutropenia in the adult and elderly patient. Haematologica 2014;99;1130–3.
Frater JL. How I investigate neutropenia. Int J Lab Hematol 2020;42;121–32.
Fioredda F, Calvillo M, Bonanomi S, Coliva T, Tucci F, Farruggia P, et al. Congenital and acquired neutropenias consensus guidelines on therapy and follow-up in childhood from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica). Am J Hematol 2012;87;238–43.
Jacobs P. Letter: Familial benign chronic neutropenia. S Afr Med J 1975;49;692.
Dale DC, Person RE, Bolyard AA, Aprikyan AG, Bos C, Bonilla MA, et al. Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. Blood 2000;96;2317–22.
Newburger PE, Pindyck TN, Zhu Z, Bolyard AA, Aprikyan AAG, Dale DC, et al. Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes. Pediatr Blood Cancer 2010;55;314–17.
Lange RD. Cyclic hematopoiesis: human cyclic neutropenia. Exp Hematol 1983;11;435–51.
Donowitz GR, Maki DG, Crnich CJ, Pappas PG, Rolston KVI. Infections in the neutropenic patient—new views of an old problem. Hematology Am Soc Hematol Educ Program 2001;113–39.
Shi X, Sims MD, Hanna MM, Xie M, Gulick PG, Zheng YH, et al. Neutropenia during HIV infection: adverse consequences and remedies. Int Rev Immunol 2014;33;511–36.
Anabire NG, Aryee PA, Helegbe GK. Hematological abnormalities in patients with malaria and typhoid in Tamale Metropolis of Ghana. BMC Res Notes 2018;11;353.
Hammond WP, Harlan JM, Steinberg SE. Severe neutropenia in infectious mononucleosis. West J Med 1979;131;92–7.
Almeida-Porada GD, Ascensăo JL. Cytomegalovirus as a cause of pancytopenia. Leuk Lymphoma 1996;21;217–23.
Sari R, Buyukberber N, Sevinc A, Bayindir Y, Buyukberber S. Brucellosis in the etiology of febrile neutropenia: case report. J Chemother 2002;14;88–91.
Levine AM, Karim R, Mack W, Gravink DJ, Anastos K, Young M, et al. Neutropenia in human immunodeficiency virus infection: data from the women’s interagency HIV study. Arch Intern Med 2006;166;405–10.
Massoll AF, Powers SC, Betten DP. Agranulocytosis occurrence following recent acute infectious mononucleosis. Am J Emerg Med 2017;35;803.e5–803.e6.
Reilly JP, Anderson BJ, Hudock KM, Dunn TG, Kazi A, Tommasini A, et al. Neutropenic sepsis is associated with distinct clinical and biological characteristics: a cohort study of severe sepsis. Crit Care 2016;20;222.
Tesfa D, Keisu M, Palmblad J. Idiosyncratic drug-induced agranulocytosis: possible mechanisms and management. Am J Hematol 2009;84;428–34.
Andrès E, Zimmer J, Mecili M, Weitten T, Alt M, Maloisel F. Clinical presentation and management of drug-induced agranulocytosis. Expert Rev Hematol 2011;4;143–51.
Castillo LEM, Palmer S, Deal A, Chen SL, Zhu A, Moll S. Incidence and time course of neutropenia in patients treated with rituximab-based therapy for non-malignant immune-mediated hematologic diseases. Blood 2019;134;390.
Wolach O, Bairey O, Lahav M. Late-onset neutropenia after rituximab treatment: case series and comprehensive review of the literature. Medicine (Baltimore) 2010;89;308–18.
Juliá A, Olona M, Bueno J, Revilla E, Rosselló J, Petit J, et al. Drug-induced agranulocytosis: prognostic factors in a series of 168 episodes. Br J Haematol 1991;79;366–71.
Crist WM, Parmley RT, Holbrook CT, Castleberry RP, Denys FR, Malluh A. Dysgranulopoietic neutropenia and abnormal monocytes in childhood vitamin B12 deficiency. Am J Hematol 1980;9;89–107.
Chin A. Copper deficiency anemia and neutropenia due to ketogenic diet. Pediatrics 2018;141;e20173286.
Socha DS, DeSouza SI, Flagg A, Sekeres M, Rogers HJ. Severe megaloblastic anemia: vitamin deficiency and other causes. Cleve Clin J Med 2020;87;153–64.
Vallurupalli M, Divakaran S, Parnes A, Levy BD, Loscalzo J. The element of surprise. N Engl J Med 2019;381;1365–71.
Hütter G, Ganepola S, Hofmann WK. The hematology of anorexia nervosa. Int J Eat Disord 2009;42;293–300.
Starkebaum G. Chronic neutropenia associated with autoimmune disease. Semin Hematol 2002;39;121–7.
Capsoni F, Sarzi-Puttini P, Zanella A. Primary and secondary autoimmune neutropenia. Arthritis Res Ther 2005;7;208–14.
Lamy T, Moignet A, Loughran TP. LGL leukemia: from pathogenesis to treatment. Blood 2017;129;1082–94.
Weinzierl EP, Arber DA. The differential diagnosis and bone marrow evaluation of new-onset pancytopenia. Am J Clin Pathol 2013;139;9–29.
Papadaki HA, Eliopoulos AG, Kosteas T, Gemetzi C, Damianaki A, Koutala H, et al. Impaired granulocytopoiesis in patients with chronic idiopathic neutropenia is associated with increased apoptosis of bone marrow myeloid progenitor cells. Blood 2003;101;2591–600.
Papadaki HA, Stamatopoulos K, Damianaki A, Gemetzi C, Anagnostopoulos A, Papadaki T, et al. Activated T-lymphocytes with myelosuppressive properties in patients with chronic idiopathic neutropenia. Br J Haematol 2005;128;863–76.
Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, 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;31;794–810.
Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med 2007;146;657–65.
Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP. The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood 1997;89;256–60.
Lucas G, Porcelijn L, Fung YL, Green F, Reil A, Hopkins M, et al. External quality assessment of human neutrophil antigen (HNA)-specific antibody detection and HNA genotyping from 2000 to 2012. Vox Sang 2013;105;259–69.
Dale DC. How I diagnose and treat neutropenia. Curr Opin Hematol 2016;23;1–4.
Mehta HM, Malandra M, Corey SJ. G-CSF and GM-CSF in neutropenia. J Immunol 2015;195;1341–9.
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Solomou, E.E., Salamaliki, C. & Lagadinou, M. How to Make the Right Diagnosis in Neutropenia. Clin Hematol Int 3, 41–46 (2021). https://doi.org/10.2991/chi.k.210216.001
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DOI: https://doi.org/10.2991/chi.k.210216.001