hematology and oncology
Neutropenia
Etiology of Neutropenia
Acute neutropenia(occurring over hours to a few days) can develop as a result of Rapid neutrophil use or destruction Impaired neutrophil production Chronic neutropenia(lasting months to years) usually arises as a result of Reduced production Excessive splenic sequestration Neutropenia also may be classified as Primary due to an intrinsic defect in marrow myeloid cells Secondary due to factors extrinsic to marrow myeloid cells See also the table Classification of Neutropenias . Neutropenia caused by intrinsic defects in myeloid cells or their precursors is uncommon ( Etiology references ). When present, the Chronic idiopathic neutropenia Congenital neutropenia Chronic idiopathic neutropeniais a type of chronic neutropenia in which the rest of the immune system appears to remain intact. Even when neutrophil counts are<200/mcL (< 0.2 × 109/L), severe infections are infrequent, probably because neutrophils are produced in adequate quantities in response to infection. It is more common in women. Severe congenital neutropenia(SCN) is a heterogenous group of rare disorders that are characterized by an arrest in myeloid maturation at the promyelocyte stage in the bone marrow, resulting in an absolute neutrophil count of<200/mcL (< 0.2 × 109/L) and significant infections starting in infancy. Severe congenital neutropenia is usually inherited in an autosomal dominant fashion but can be recessive, X-linked, or sporadic. ). Almost all patients with severe congenital neutropenia will respond to G-CSF therapy, but Hematopoietic Stem Cell Transplantation may be needed for patients who respond poorly to G-CSF and those who develop Cyclic neutropeniais a rare congenital granulocytopoietic disorder, usually transmitted in an autosomal dominant fashion and usually caused by a mutation in the gene for neutrophil elastase (ELANE), that results in apoptosis. It is characterized by regular, periodic oscillations in the number of peripheral neutrophils. The mean oscillatory period is 21±3 days. Cycling of other blood cells is also evident in most cases. occurs in members of some ethnic groups (eg, some people of African, Middle Eastern, or Jewish ancestry). Patients normally have lower neutrophil counts but do not have increased risk of infection. In some cases, this finding has been linked to the Duffy red blood cell antigen; some experts think neutropenia in these populations is related to protection from Malaria . (eg, cartilage-hair hypoplasia syndrome, Chédiak-Higashi Syndrome , dyskeratosis congenita, glycogen storage disease type Ib, Shwachman-Diamond syndrome, warts, hypogammaglobulinemia, infections, myelokathexis [WHIM] syndrome) can involve bone marrow failure that causes neutropenia. Neutropenia is also a feature of Myelodysplastic Syndrome (MDS) , where it may be accompanied by megaloblastoid features in the bone marrow, and of Secondary neutropenia can result from use of certain drugs, bone marrow infiltration or replacement, certain infections, or immune reactions. Themost common causesinclude Drugs Infections and immune reactions Marrow infiltrative processes Drug-induced neutropeniais one of the most common causes of neutropenia. Drugs can decrease neutrophil production through toxic, idiosyncratic, or hypersensitivity mechanisms; or they can increase peripheral neutrophil destruction through immune mechanisms. Only the toxic mechanism causes dose-related neutropenia. Severe dose-related neutropenia occurs predictably after administration of cytotoxic cancer drugs, phenothiazine, or radiation therapy due to suppression of bone marrow production. Idiosyncratic reactions are unpredictable and occur with a wide variety of drugs, including alternative medicine preparations or extracts, and toxins. Drug Hypersensitivity are rare and occasionally involve antiseizure drugs (eg, Immune-mediated drug-induced neutropenia, thought to arise from drugs that act as haptens to stimulate antibody formation, usually persists for about 1 week after the drug is stopped. It may result from aminopyrine,clozapine,propylthiouraciland other antithyroid drugs, penicillin, or other antibiotics. can occur in Megaloblastic Macrocytic Anemias caused by vitamin B12 deficiency or folate deficiency. Usually, macrocytic anemia and sometimes mild thrombocytopenia develop simultaneously. Ineffective production can also accompany by Overview of Leukemia , Splenomegaly None can cause neutropenia by impairing neutrophil production or by inducing immune destruction or rapid turnover of neutrophils. Sepsis and Septic Shock is a particularly serious cause. Neutropenia that occurs with common childhood viral diseases develops during the first 1 to 2 days of illness and may persist for 3 to 8 days. Transient neutropenia may also result from virus- or endotoxemia-induced redistribution of neutrophils from the circulating to the marginal pool. Alcohol may contribute to neutropenia by inhibiting the neutrophilic chemotactic response of the marrow during some infections (eg, pneumococcal pneumonia). Immune defectscan cause neutropenia. Neonatal isoimmune neutropenia can occur with fetal/maternal neutrophil antigen incompatibility associated with transplacental transfer of IgG antibodies against the newborn’s neutrophils (most commonly to human neutrophil antigen [HNA-1]). Autoimmune neutropenia can occur at any age and may be operative in many cases of idiopathic chronic neutropenia. Testing for antineutrophil antibodies (immunofluorescence, agglutination, or flow cytometry) is not always available or reliable. Autoimmune neutropenias may be acute, chronic, or episodic. They may involve antibodies directed against circulating neutrophils or neutrophil precursor cells. They may also involve cytokines (eg, gamma interferon, tumor necrosis factor) that can cause neutrophil apoptosis. Most patients with autoimmune neutropenia have an underlying autoimmune disorder or lymphoproliferative disorder (eg, large granular lymphocyte [LGL syndrome [a clonal disease of large granular lymphocytes], Systemic Lupus Erythematosus (SLE) , Felty syndrome). Chronic secondary neutropenia often accompanies 1.Dale DC: How I diagnose and treat neutropenia.Curr Opin Hematol23(1):1-4, 2016. doi: 10.1097/MOH.0000000000000208 2.Skokowa J, Dale DC, Touw IP, et al: Severe congenital neutropenias.Nat Rev Dis Primers3:17032, 2017. doi: 10.1038/nrdp.2017.32 