Döhle bodies

Figure 10.2 The evolution of toxic granulation.

Figure 10.3 Toxic granulation. Note heavier granulation throughout the cytoplasm.

Toxic Granulation

Normal granulation in the segmented neutrophils shows a dustlike appearance, with the red and blue granules being difficult to observe. Toxic granulation is excessive granulation in amount and intensity, with more prominent granules in segmented neutrophils in direct response to enhanced lysosome enzyme production. These granules are more frequent and have much more vivid blue-black coloration (Fig. 10.3). Cluster of toxic granules usually appear in neutrophils. At times the granulation is so heavy as to resemble basophilic granules.

Toxic Vacuolization

This change occurs in segmented neutrophils. Vacuoles appear in the cytoplasm of this cell and may be small or large (Fig. 10.4). Prolonged exposure of blood to drugs

Figure 10.4 Toxic vacuolization. Note large vacuoles located in the cytoplasm.

Table 10.2


Essential Elements Leading to Phagocytosis

Figure 10.4 Toxic vacuolization. Note large vacuoles located in the cytoplasm.

• Neutrophils: Attracted to pathogen, are activated by endothelial cell surface receptors, will recruit more neutrophils to infection site through cell surface receptors

• Monocytes: Cells in transit between marrow, tissues circulating blood, will move to area of stimuli and possess lytic enzymes

• Basophils, eosinophils: React in concert with complement and hormones to suppress inflammation


• C5a: Coats the pathogen, making it "tasty" to phago-cytic cells

• C3b: Causes increase in vascular permeability


• Tumor necrosis factor

such as sulfonamides or chloroquine or prolonged storage may lead to phagocytosis of granules or cyto-plasmic contents.5 Additionally, small uniformly placed vacuoles may be seen in peripheral smear made from blood that has held for long periods of time. In cases where the creation of peripheral smears has been delayed, pseudo-vacuolization will be recognized. This phenomenon must be distinguished from the pathogenic variety. Larger vacuoles unevenly distributed throughout the cytoplasm usually signal serious infections and possible sepsis. Studies have shown that when 10% of neutrophils are affected by vacuoles in a fresh sample, this ranks as a serious and significant prognostic indicator6 (Table 10.3).

Table 10.3 O Significant Alterations in Neutrophils in Peripheral Smears

Dohle bodies

Toxic granulation

Toxic vacuolization



Bacteria (intracellular or extracellular)

Platelet satellitism

Chediak-Higashi granules

148 Part III • White Cell Disorders

148 Part III • White Cell Disorders

Figure 10.5 Dohle bodies are inclusions that are pale, peripherally located in the cytoplasm, and rodlike.

Dohle Bodies

These cytoplasmic inclusions consist of ribosomal RNA. They range from 1 to 5 pm in size, are located near the cytoplasmic membrane, and appear as a rod-shaped pale bluish-gray structure (Fig. 10.5). These transient inclusions are frequently observed in neutrophils but may be seen in monocytes and bands. Dohle bodies are difficult to observe under light microscopy, and peripheral smears must be carefully scrutinized for their presence. Dohle bodies may also be seen in nonpathological conditions such as pregnancy.

Human Ehrlichiosis

Named for the noted microbiologist, Paul Ehrlich, human ehrlichiosis infections are a fairly new group of tick-borne diseases, which show a notable white cell inclusion in some cases. There are two varieties: human monocytic ehrlichiosis (HME), caused by the Rickettsia-like bacteria Ehrlichia chafeensis, and human granulo-cytic ehrlichiosis (HE), caused by the Rickettsia-like bacteria Ehrlichia phagocytophilia. These diseases are difficult to diagnose because patients show vague symptomatology that is often mistaken for other infectious diseases. HME cases are usually located in the southeastern and mid-Atlantic United States9 and show in initial flu-like presentation. Patients with HE, who are usually located in the midwestern United States, show an acute onset of high fever, chills, and headache.10 Common to both illnesses is low white count, extremely elevated liver enzymes, and thrombocytopenia. Inclusions may be seen in the granulocytes or monocytes from the bone marrow, and these morula, mulberry-like, inclusions are large, 1 to 3 pm, and resemble berries in appearance

Figure 10.6 Human ehrlichiosis.

(Fig. 10.6). These inclusions, if identified, are specific for these diseases but are difficult to observe and are not seen in every case. However, peripheral smears and bone marrow smears should be carefully reviewed for identification of these inclusion bodies.

Nuclear Abnormalities: Hypersegmentation

Normal segmented neutrophils will have between three and five lobes in the nucleus. Hypersegmentation is defined as a segmented neutrophilic nucleus having more than five lobes (Fig. 10.7). This condition is usually seen in the megaloblastic processes such as folic acid, pernicious anemia, or vitamin B12 deficiency and is usually accompanied by oval macrocytes.

Figure 10.7 Hypersegmented neutrophil.

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