2691 ## Clinical Features 2692 2693 The signs and symptoms of neutropenia are related to infection and include malaise, chills, and fever, often followed by marked weakness and fatigability. With agranulocytosis, infections are often overwhelming and may cause death within hours to days. 2694 2695 Serious infections are most likely when the neutrophil count falls below 500/μL3. Because infections are often fulminant, broad-spec-trum antibiotics must be given expeditiously whenever signs or symptoms appear. In some instances, such as following myelosup-ressive chemotherapy, neutropenia is treated with G-CSF, a growth factor that stimulates the production of granulocytes from marrow precursors. 2696 2697 2698 2699 2700 ## REACTIVE PROLIFERATIONS OF WHITE CELLS 2701 AND LYMPH NODES 2702 2703 2704 ## Leukocytosis 2705 2706 Leukocytosis refers to an increase in the number of white cells in the blood. It is a common reaction to a variety of inflammatory states. 2707 2708 2709 ## Pathogenesis 2710 2711 The peripheral blood leukocyte count is influenced by several factors, including: 2712 - The size of the myeloid and lymphoid precursor and storage cell pools in the bone marrow, thymus, circulation, and peripheral tissues. 2713 - The rate of release of white cells from the storage pools into the circulation. 2714 - The proportion of white cells that are adherent to blood vessel walls at any time (the marginal pool). 2715 - The rate of extravasation of white cells from the blood into tissues. 2716 2717 As discussed in Chapter 3, leukocyte homeostasis is maintained by cytokines, growth factors, and adhesion molecules through their effects on the proliferation, differentiation, and extravasation of leuko-cytes and their progenitors. Table 13.2 summarizes the major mecha-nisms of neutrophilic leukocytosis and its causes, the most important of which is infection. In acute infection there is a rapid increase in the egress of mature granulocytes from the bone marrow pool, an altera-tion that may be mediated through the effects of tumor necrosis factor (TNF) and interleukin-1 (IL-1). If the infection or an inflammatory process is prolonged, IL-1, TNF, and other inflammatory mediators 2718 2719 *TABLE 13.2 Mechanisms and Causes of Leukocytosis* 2720 2721 2722

Increased Marrow Production
Chronic infection or inflammation (growth factor-dependent)
Paraneoplastic (e.g., Hodgkin lymphoma; growth factor-dependent)
Myeloproliferative neoplasms (e.g., chronic myeloid leukemia; growth factor-independent)
Increased Release From Marrow Stores
Acute inflammation (e.g., with infection)
Chronic inflammation (multiple causes)
Decreased Margination
Exercise
Catecholamines
Decreased Extravasation Into Tissues
Glucocorticoids

2723 2724 *TABLE 13.3 Causes of Leukocytosis* 2725 2726 2727

Type of Leukocytosis	Causes
Neutrophilic leukocytosis	Acute bacterial infections, especially those caused by pyogenic organisms; sterile inflammation caused by, for example, tissue necrosis (myocardial infarction, burns)
Eosinophilic leukocytosis (eosinophilia [... Output truncated due to length. 3430 tokens/14186 characters removed ...]