Defects in neutrophil function are relatively rare inherited disorders and tend to be associated with a marked susceptibility to bacterial and fungal infection. Chronic granulomatous disease (CGD) is a disorder of white blood cells that results
Drugs: idiosyncratic, cytotoxic (myelosuppressive) Radiation Chemicals: DDT, benzene Immune-mediated: T and B cell and immunoglobulin Infections (viruses, rickettsia) Infiltrative processes: tumor, storage disease Myelodysplasia Aplastic anemia
Kostmann syndrome (HAX-1, G6PC3, ELA-2, G-CSF, GFI-1) Cyclic neutropenia (ELA-2) Cartilage hair hypoplasia Shwachman-Diamond syndrome Diamond-Blackfan syndrome Griscelli syndrome Chédiak-Higashi syndrome WHIM syndrome (warts, hypogammaglobulinemia, infections,
Pseudoneutropenia: Shift to Bone Marrow
Destruction: neonatal isoimmune, autoimmune, hypersplenism Autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome)
Leukoagglutination: lung, after cardiac bypass surgery
ELA-2, Elastase 2; G6PC3, glucose-6-phosphatase catalytic subunit 3; G-CSF, granulocyte colony-stimulating factor; GFI-1, growth factor independent 1;
HAX-1, HS1-associated protein X-1.
from defective intracellular killing of bacteria and intracellular pathogens by neutrophils and macrophages because of an inability to activate the “respiratory burst,” the catalytic conversion of molecular oxygen to superoxide (O2–). Reduced nicotinamide adenine dinucleotide phosphate oxidase, the enzyme that catalyzes the respiratory burst, consists of four subunits; gp91phox, p22phox, p47phox, and p67phox. Defects in any of these enzymes lead to an inability to kill catalase-positive pathogens such as S. aureus and enteric gram-negative bacteria (Burkholderia) and fungi (Aspergillus fumigatus, Candida albicans). The gp91phox gene is located on chromosome Xp21.1 and is responsible for the most common form of the disease. The other gene defects are inherited in an autosomal recessive manner. The chromosome locations for
HIV, human immunodeficiency virus.
Table 74-4 Drug-Associated Neutropenia CYTOTOXIC Myelosuppressive, chemotherapeutic agents Immunosuppressive agents IDIOSYNCRATIC
Indomethacin Para-aminophenol derivatives Pyrazolone derivatives (aminopyrine, dipyrone, oxyphenbutazone) Chloramphenicol Sulfonamides Antithyroid drugs (propylthiouracil, methimazole, carbimazole) Phenothiazines (chlorpromazine, phenothiazines) Penicillins and semisynthetic penicillins
Adapted from Dale DC: Neutropenia. In Lichtman MA, Kipps TJ, Seligsohn U, et al, editors: Williams Hematology, ed 8, New York, 2010, McGraw-Hill.