Page 1409 - Small Animal Internal Medicine, 6th Edition

CHAPTER 86
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Combined Cytopenias

and Leukoerythroblastosis

DEFINITIONS AND CLASSIFICATION (2) the crowding out of normal BM precursors (e.g., leuke-
mia, BM lymphoma). They may also be prematurely released
Combined cytopenias commonly result from decreased from a site of extramedullary hematopoiesis (EMH) (i.e.,
bone marrow (BM) production or, less frequently, from spleen, liver) as a result of the absence of normal feedback
increased destruction or sequestration of circulating cells. mechanisms. Because the nuclei of the nRBCs are pitted
The following terms are used throughout this chapter. Bicy- primarily in the spleen, splenectomized patients may have
topenia is a decrease in the numbers of two circulating blood LERs. Recently, the presence of circulating nRBCs (normo-
cell lines (anemia and neutropenia, anemia and thrombocy- blastemia) in dogs undergoing anticancer chemotherapy was
topenia, or neutropenia and thrombocytopenia). If all three well characterized (Moretti et al., 2015). In addition, normo-
cell lines are affected (anemia, neutropenia, thrombocytope- blastemia is commonly seen in healthy Miniature Schnau-
nia), this is termed pancytopenia (from the Greek word pan, zers and in Dachshunds.
meaning “all”). When evaluating a complete blood count
(CBC) for leukopenia, it is best to evaluate only the neutro-
phils (i.e., neutropenia) because in some patients with neo- CLINICOPATHOLOGIC FEATURES
plastic or reactive lymphocytosis, the total white blood cell
(WBC) count may be normal or even high, but the neutro- The clinical signs and physical examination findings in dogs
phil count is low. In most cases, if anemia is present, it is and cats with combined cytopenias or LERs are usually
nonregenerative. If regenerative anemia occurs in associa- related to the underlying disorder rather than the hemato-
tion with other cytopenias, the cause usually is peripheral logic abnormalities per se, with the exception of pallor and
destruction of cells. A leukoerythroblastic reaction (LER, or spontaneous bleeding (petechiae, ecchymoses) secondary to
leukoerythroblastosis) refers to the presence of immature anemia and thrombocytopenia, respectively. Pyrexia may be
WBCs (left shift) and nucleated red blood cells (nRBCs) in present if the patient is markedly neutropenic and is septic
the circulation. In these cases, the WBC count is usually or bacteremic.
high, but it can be normal or low. An important aspect of the clinical evaluation of these
As noted, cytopenias can develop as a result of decreased patients is the history. A detailed history should be obtained,
production or increased peripheral destruction of the affected inquiring specifically about the therapeutic use of drugs (e.g.,
cell line(s). In general, bicytopenias and pancytopenias result estrogen or phenylbutazone in dogs, griseofulvin or chlor-
from primary BM disorders (i.e., there is a problem in the amphenicol in cats), exposure to benzene derivatives (rare),
“cell factory”; Box 86.1), although they may also result from travel history, vaccination status, and exposure to other
peripheral blood cell destruction, such as what occurs in animals, among others. Most drugs that cause anemia or
sepsis, disseminated intravascular coagulation (DIC), and neutropenia can also cause combined cytopenias (see Boxes
some infectious and immune-mediated diseases. 82.2 and 85.1).
LERs result from a variety of mechanisms (Box 86.2), but The physical examination of dogs and cats with com-
in general the presence of immature blood cells in the circu- bined cytopenias may reveal the presence of spontaneous
lation is secondary to their premature release from the BM hemorrhages compatible with a primary hemostatic disorder
or from other hematopoietic organs (spleen, liver). This pre- (e.g., thrombocytopenia) or pallor secondary to the anemia.
mature release can result from the following: (1) an increased Several physical examination findings may help the clini-
demand for blood cells (e.g., hemolytic anemia, blood loss, cian establish a more presumptive or definitive diagnosis
peritonitis), resulting in a shorter transit time through the in patients with cytopenias or LER. Of particular interest is
BM compartments or extramedullary hematopoietic sites; or the finding of male-feminizing signs in a male dog (usually

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