Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 13-22: Neutropenia + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Neutrophils < 1800/mcL Severe neutropenia if neutrophils < 500/mcL +++ General Considerations ++ Patients with neutropenia are vulnerable to gram-positive and gram-negative bacterial and fungal infections Risk of infection is related to the severity of neutropenia Patients with "chronic benign neutropenia" are free of infection despite very low stable neutrophil counts In patients with cyclic neutropenia, the neutrophil count oscillates (usually in 21-day cycles) between normal and low, with infections occurring during the nadirs Congenital neutropenia is lifelong neutropenia punctuated with infection Both cyclic neutropenia and congenital neutropenia represent problems in mutations in the neutrophil elastase gene ELANE (also called ELA-2) +++ Etiology ++ A variety of bone marrow disorders and nonmarrow conditions may cause neutropenia (Table 13–12) All the causes of aplastic anemia and pancytopenia may cause neutropenia Causes of aplastic anemia Autoimmune: idiopathic, systemic lupus erythematosus Congenital: defects in telomere length maintenance or DNA repair (rare) Chemotherapy, radiotherapy Toxins: benzene, toluene, insecticides Medications: chloramphenicol, gold salts, sulfonamides, phenytoin, carbamazepine, quinacrine, tolbutamide Post-viral hepatitis (A, B, C, E, G, non-A through -G) Non-hepatitis viruses (Epstein-Barr virus, parvovirus, cytomegalovirus, echovirus 3, others) Pregnancy Paroxysmal nocturnal hemoglobinuria Causes of pancytopenia Aplastic anemia Myelodysplasia Acute leukemia Chronic idiopathic myelofibrosis Infiltrative disease: lymphoma, myeloma, carcinoma, hairy cell leukemia, etc Hypersplenism (with or without portal hypertension) Systemic lupus erythematosus Infection: tuberculosis, HIV, leishmaniasis, brucellosis, cytomegalovirus, parvovirus B19 Nutritional deficiency (megaloblastic anemia) Medications Cytotoxic chemotherapy Ionizing radiation New onset of an isolated neutropenia is most often due to an idiosyncratic reaction to a drug Agranulocytosis (complete absence of neutrophils in the peripheral blood) is almost always due to a drug reaction Neutropenia in the presence of a normal bone marrow may be due to Immunologic peripheral destruction (autoimmune neutropenia) Sepsis Hypersplenism Isolated neutropenia is an uncommon presentation of hairy cell leukemia or a myelodysplastic syndrome Myelosuppressive cytotoxic chemotherapy causes neutropenia in a predictable manner ++Table Graphic Jump LocationTable 13–12.Causes of neutropenia.View Table||Download (.pdf) Table 13–12. Causes of neutropenia. Bone marrow disorders Congenital Dyskeratosis congenita Fanconi anemia Cyclic neutropenia Congenital neutropenia Hairy cell leukemia Large granular lymphoproliferative disorder Myelodysplasia Non–bone marrow disorders Medications: antiretroviral medications, cephalosporins, chlorpromazine, chlorpropamide, cimetidine, methimazole, myelosuppressive cytotoxic chemotherapy, penicillin, phenytoin, procainamide, rituximab, sulfonamides Aplastic anemia Benign chronic neutropenia Pure white cell aplasia Hypersplenism Sepsis Other immune Autoimmune (idiopathic) Felty syndrome Systemic lupus erythematosus HIV infection + Clinical Findings Download Section PDF Listen +++ ++ Neutropenia results in Stomatitis Infections due to gram-positive or gram-negative aerobic bacteria or to fungi such as Candida or Aspergillus Most common infectious syndromes Septicemia Cellulitis Pneumonia Neutropenic fever of unknown origin Fever should always be assumed to be of infectious origin until proven otherwise + Diagnosis Download Section PDF Listen +++ ++ Neutrophil count < 1800/mcL In certain population groups (eg, blacks, Asians), normal neutrophil counts may be as low as 1200/mcL or even less + Treatment Download Section PDF Listen +++ ++ Depends on its cause Potential causative drugs should be discontinued Myeloid growth factors (filgrastim or sargramostim or biosimilar myeloid growth factors) help facilitate neutrophil recovery after offending drugs are stopped Chronic myeloid growth factor administration (daily or every other day) is effective at dampening the neutropenia seen in cyclic or congenital neutropenia When Felty syndrome leads to repeated bacterial infections, Splenectomy has been the treatment of choice However, sustained use of myeloid growth factors is effective and provides a nonsurgical alternative Autoimmune neutropenia Often responds briefly to immunosuppression with corticosteroids and is best managed with intermittent doses of myeloid growth factors Splenectomy is held in reserve for failure to respond to corticosteroids and myeloid growth factors Neutropenia associated with large granular lymphoproliferative disorder may respond to therapy with oral methotrexate, cyclophosphamide, or cyclosporine Febrile neutropenia Enteric gram-negative bacteria are of primary concern and often empirically treated with fluoroquinolones or second-generation cephalosporins For protracted neutropenia, fungal infections are problematic and empiric coverage with azoles (fluconazole for yeast and voriconazole, itraconazole, posaconazole, or isavuconazole for molds) or echinocandins is recommended Neutropenia following myelosuppressive chemotherapy is partially ameliorated by the use of myeloid growth factors + Outcome Download Section PDF Listen +++ +++ When to Refer ++ Refer to a hematologist if neutrophils are persistently and unexplainably < 1000/mcL +++ When to Admit ++ Neutropenia by itself is not an indication for hospitalization However, many patients with severe neutropenia have a serious underlying disease that may require inpatient treatment Most patients with febrile neutropenia require hospitalization to treat infection + References Download Section PDF Listen +++ + +Abdel-Azim H et al. Strategies to generate functionally normal neutrophils to reduce infection and infection-related mortality in cancer chemotherapy. Pharmacol Ther. 2019 Dec;204:107403. [PubMed: 31470030] + +Barcellini W et al. Autoimmune hemolytic anemia, autoimmune neutropenia and aplastic anemia in the elderly. Eur J Intern Med. 2018 Dec;58:77–83. [PubMed: 30527923] + +Dale DC et al. An update on the diagnosis and treatment of chronic idiopathic neutropenia. Curr Opin Hematol. 2017 Jan;24(1):46–53. [PubMed: 27841775]