The term leucopenia indicates a decrease in the number of leucocytes with respect to the normal value. In general, leucopenia occurs when there is a decrease of neutrophils and/or lymphocytes, the two most abundant white blood cell populations, in the blood. More frequently, however, a reduction in the number of cells of these leucocyte populations decreases the values for the single populations below their respective reference limits but does not cause an absolute leucopenia (that is, a decrease below the reference limit for the total white blood cell count). It is even less probable to observe leucopenia in the case that the numbers of cells in the other populations (monocytes, eosinophils, basophils) fall below their respective reference levels, since these cells are already much less numerous than neutrophils and lymphocytes.
In general, for each white blood cell population there may be a numerical decrease such that the cell count for the particular population decreases below the reference range for that cell population (absolute leucopenias) and also less marked decreases in which the number of cells remains within the reference range, but the proportion of cells of the given lineage among the total white blood cells decreases (relative leucopenias). Relative leucopenias are often associated with increased percentages of the other leucocyte populations, whose absolute number does not, however, increase. In the presence of leucocytosis or a relative leucopenia, a white blood cell differential (leucogram) must be analysed to identify in which white blood cell populations the numerical changes have occurred.
Given that there are different classes of leucocytes in the blood, the relevance of a decrease in the number of white blood cells depends on which class is involved and the function of that class. Decreases in the numbers of neutrophils, eosinophils, basophils, lymphocytes and monocytes are called neutropenia, eosinopenia, basophilic leucopenia (basopenia), lymphocytopenia and monocytopenia, respectively.
NEUTROPENIA
The term neutropenia indicates a decrease in neutrophils. The neutropenia may be absolute (a reduction in the absolute number of neutrophils with respect to the reference range) or relative (a decrease in the percentage value while the absolute number remains within the norm). Relative neutropenia is usually dependent on increases in the percentages of other white blood cell classes, in particular lymphocytes, and the pathological relevance of the finding is dependent on the cause of the increase in the other leucocyte classes rather than on a pathology able to reduce the number of neutrophils.
The most common cause of neutropenia is a very intense attraction of neutrophils to the site of inflammation, where the neutrophils are then destroyed. If the peripheral consumption is minimal, neutropenia may not be detected because the body responds by mobilising the marginal pool and bone marrow reserves: the number of mature neutrophils may not change even though a reduction in mature cells may be observed in cytological studies of the bone marrow. If, however, the attraction of neutrophils into the tissues is rapid, the body may not be able to respond adequately and a consumption neutropenia occurs, in which few mature neutrophils are present in the circulation.
If the attraction of neutrophils into tissues and the destruction of the cells are particularly intense, as usually occurs in severe bacterial infections or in the presence of extensive areas of necrosis, the pools (circulating, marginal, bone marrow) of available mature cells are rapidly exhausted and consumption neutropenia with left shift (Fig. 1) develops. This form of neutropenia is characterized by few circulating neutrophils, which are predominantly immature cells as a result of the introduction of young cells from the bone marrow into the circulation. A reduction in neutrophils without left shift can be observed in immune-mediated neutropenias in which anti-neutrophil antibodies are produced. Some of these forms of neutropenia are of autoimmune origin and often occur in association with other autoimmune haematological disorders (immune-mediated anaemia, immune-mediated thrombocytopenia) or systemic autoimmune disorders (e.g. systemic lupus erythematosus).
There may be mild neutropenia in the early stages of viral infections, due both to peripheral consumption of the neutrophils (see above) and to a lack of production of the cells by the bone marrow (see below). Decreased medullary production of neutrophils usually causes severe neutropenia. The causes of decreased production are often toxicity and infections (particularly infections of the bone marrow stroma by viruses such as Feline immunodeficiency virus, Feline leukaemia virus and Parvovirus), but may also be replacement of the bone marrow by neoplastic cells in the case of leukaemias, or bone marrow necrosis associated with sepsis or thrombosis. In these forms there is usually decreased activity of the bone marrow precursor cells so the neutropenia is part of a pancytopenia (leucopenia, anaemia, thrombocytopenia), as occurs in the case of the so-called aplastic anaemia. Some drugs, however, may act predominantly on the precursors of neutrophils (e.g. antineoplastic drugs, griseofulvin, antiviral agents, synthetic oestrogenic hormones). In these cases the neutropenia is not usually associated with cytopenia of other blood cell lineages. Finally, a particular form of neutropenia is the cyclic neutropenia that occurs in the Grey collie, a form which is characterized by recurrent neutropenic crises.
LYMPHOCYTOPENIA
The term lymphocytopenia indicates a reduction in lymphocytes. Both absolute lymphocytopenia (a decrease in the absolute number of lymphocytes) and relative lymphocytopenia (a decrease in the percentage value, usually because of a contemporaneous neutrophilia) are common.
The most frequent cause of lymphocytopenia is stress, such that lymphocytopenia is one of the haematological findings that characterize the so-called stress leucogram, together with neutrophilia, monocytosis and eosinopenia. The pathogenesis of stress-induced lymphocytopenia includes sequestration of lymphocytes in lymphoid organs, greater fragility of the cells and a reduction in lymphocyte production.
Another frequent cause of lymphocytopenia is a viral infection, particularly if caused by a lymphotropic virus (e.g. Feline immunodeficiency virus, Feline leukaemia virus), due both to direct infection of the lymphocytes, above all the CD4 lymphocytes, by the virus, and to infection of the bone marrow stroma which decreases haematopoietic activity in general.
Other consumption lymphocytopenias include inflammatory forms with attraction of lymphocytes to a site of inflammation (although in the case of inflammation it is more likely to find lymphocytosis due to immune stimulation) or a loss of lymph (e.g. due to rupture of the thoracic duct) associated with a chylous effusion.
Finally, there are forms of lymphocytopenia due to decreased production caused by toxic phenomena (e.g. anti-neoplastic drugs), malnutrition, specific or non-specific immune deficiencies (e.g severe combined immunodeficiency or SCID) or neoplasms such as lymphoma, in which, apart from the more advanced stages in which there is bone marrow involvement (stage V), the neoplastic proliferation may be confined to the lymphoid organs and not be associated with entry of neoplastic cells into the circulation.
EOSINOPENIA
The term eosinopenia indicates a decrease in eosinophils. Eosinopenia is often relative (a decrease in the percentage of eosinophils because of an increase in the other white blood cell populations) while more rarely there is an absolute eosinopenia (a decrease in the absolute number of eosinophils). While relative eosinopenia does not have a particular clinical relevance, if not that associated with the increased numbers of the other types of leucocytes, it is often associated with stress, in which it occurs together with lymphocytopenia, neutrophilia and, in the dog, monocytosis.
MONOCYTOPENIA
The term monocytopenia indicates a reduction in the number of monocytes. Monocytopenia can be absolute (a reduction in the absolute number) or relative (a decrease in the percentage value). This latter is more frequent and occurs in cases of neutrophilia, eosinophilia and lymphocytosis. The pathological relevance of relative monocytopenia should be looked for in the cause of the increase in the other white blood cell populations, while absolute monocytopenia is not of particular clinical relevance.
BASOPHILIC LEUCOPENIA
The number of basophils in the circulation is extremely low so a decrease in this cell population, although theoretically included among the leucopenias, is not usually found.
Suggested reading
- Feldman B.F., Zinkl J.G., Jain N.C.: Schalm’s Veterinary Hematology, 5a edizione. Philadelphia: Lippincott Williams & Wilkins, 2000.
- Stockham S.L., Scott M.A.: Fundamentals of Veterinary Clinical Pathology, 2a edizione. Blackwell Publishing, 2008.
- Comazzi S, Pieralisi C, Bertazzolo W. Haematological and biochemical abnormalities in canine blood: frequency and associations in 1022 samples. J Small Anim Pract. 2004 Jul;45(7):343-9.
- Brown MR, Rogers KS Neutropenia in Dogs and Cats: A Retrospective Study of 261 Cases J Am Anim Hosp Assoc 2001;37:131–139.
- Paltrinieri S., Bertazzolo W., Giordano A. Patologia Clinica del Cane e del gatto. Approccio pratico alla diagnostica di laboratorio. ISBN: 978-88-2143-159-3. Elsevier Masson, 2010.