Leukopenia results most commonly from a decrease in granulocytes, the most numerous circulating white cells. Lymphopenia is much less common; it is associated with rare congenital immunodeficiency diseases, advanced human immunodeficiency virus (HIV) infection, and treatment with high doses of corticosteroids. Only the more common leukopenias of granulocytes are discussed here.
A reduction in the number of granulocytes in blood is known as neutropenia or, when severe, agranulocytosis. Neutropenic persons are susceptible to severe, potentially fatal bacterial and fungal infections. The risk of infection rises sharply as the neutrophil count falls below 500 cells/µL.
The mechanisms underlying neutropenia can be divided into two broad categories:
Decreased granulocyte production. Clinically important reductions in granulopoiesis are most often caused by marrow hypoplasia (as occurs transiently with cancer chemotherapy and chronically with aplastic anemia) or extensive replacement of the marrow by tumor (such as with leukemia). Alternatively, neutrophil production may be suppressed while other blood lineages are unaffected. This is most often caused by certain drugs or by neoplastic proliferations of cytotoxic T cells and natural killer (NK) cells (so-called “large granular lymphocytic leukemia”).
Increased granulocyte destruction. This can be encountered with immune-mediated injury (triggered in some cases by drugs) or in overwhelming bacterial, fungal, or rickettsial infections resulting from increased peripheral use. Splenomegaly also can lead to the sequestration and accelerated removal of neutrophils.
MORPHOLOGYThealterationsinthebonemarrowdependontheunderlyingcause.Compensatorymarrowhypercellularityisseenwhenthereisexcessiveneutrophildestructionorineffectivegranulopoiesis,suchasoccursinmegaloblasticanemia.Drugsthatselectivelysuppressgranulocytopoiesisareassociatedwithdecreasednumbersofgranulocyticprecursorsandpreservationoferythroidelementsandmegakaryocytes,whilemyelotoxicchemotherapydrugsreducethenumberofelementsfromalllineages.
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Clinical Features. Infections constitute the major problem. They commonly take the form of ulcerating, necrotizing lesions of the gingiva, floor of the mouth, buccal mucosa, pharynx, or other sites within the oral cavity (agranulocytic angina). Owing to the lack of leukocytes, such lesions often contain large masses or sheets of microorganisms. In addition to local inflammation, systemic symptoms usually are present consisting of malaise, chills, and fever. Because of the danger of sepsis, patients are started on broad-spectrum antibiotics covering both bacterial and fungal infections at the first sign of infection. Depending on the clinical context, patients also may be treated with granulocyte colony-stimulating factor (G-CSF), a growth factor that speeds recovery of neutrophil counts.
An increase in the number of white cells in the blood is common in a variety of inflammatory states caused by microbial and nonmicrobial stimuli. Leukocytoses are relatively nonspecific and are classified according to the particu lar white cell series that is affected (Table 12.6).
As discussed later, in some cases reactive leukocytosis may mimic leukemia. Such “leukemoid reactions” must be distinguished
Table 12.6 Causes of Leukocytosis
Acutebacterialinfections(especiallythosecausedbypyogenicorganisms);sterileinflammationcausedby,e.g.,tissuenecrosis(myocardialinfarction,burns)