Rarely, degenerate leukocyte forms (Fig. 9 a) may be found in the peripheral blood of patients exposed to certain irritants. They are more commonly seen in smears prepared from long-stored blood previously treated with EDTA or citrate solution. Most of these cells have the same diameter as segmented forms, but many are considerably smaller (4-8 im). Usually their cytoplasm is slightly more basophilic than in segmented forms, and their granules are coarser and often smudged. Pronounced nuclear pyknosis is typical, and 3-5 solid, featureless nuclear remnants may be found scattered like droplets in the cytoplasm. There are few if any filaments interconnecting the nuclear remnants.
In cases of severe infection or bone marrow injury, it is common to find large purple granules in the myelocytes and in more mature stages up to the segmented forms. Often they are similar to the granules seen in promyelocytes, and many authors consider them to be identical. This "toxic granulation" (Fig. 9 b) is variable in its intensity. In very pronounced cases the neutrophils may come to resemble basophilic granulocytes.
Cytoplasmic vacuoles in leukocytes, like toxic granulations, can develop in response to various toxic insults. They are often observed during long-term chloramphenicol therapy, phenylketo-nuria, diabetes mellitus, and in the setting of severe bacterial and viral infections. The vacuoles reflect a metabolic disturbance in the affected cells.
Heparin artifact. Adding heparin to peripheral blood or especially bone marrow before preparing smears leads to artifacts when a panoptic stain is used (Giemsa or Pappenheim): the cells show scant or atypical staining, and a purple, crumbly precipitate forms on the background, making it difficult or impossible to identify the cells (Fig. 9 c).
Necrotic bone marrow. Bone marrow that has been aspirated and stained may be found to contain unstructured purple material or faint, shadowy cells with indistinct outlines. The cause is necrotic bone marrow at the aspiration site. The necrosis may be quite extensive and is occasionally seen in acute leukemias and other diseases (Fig. 9 d).
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