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Top 5 Leukogram Patterns TOP 5 > DIAGNOSTICS > PEER REVIEWED Top 5 Leukogram Patterns Sarah Schmidt, DVM, DACVP (Clinical Pathology)* Ashland, Massachusetts A CBC is often completed as part of the minimum database. When the CBC is per- formed with an in-house hematology analyzer, a blood smear evaluation should be pursued as well to verify automated results, including confirmation of white blood cell (WBC) differential and evaluation for atypical cells, such as mast cells, blasts, and nucleated red blood cells. Following confirmation of automated results, evaluation of the leukogram, which includes total WBC count, absolute values of individual leuko- cytes, and leukocyte morphology, should be performed to identify any pattern. When evaluating WBC differentials, absolute cell numbers (WBC count × leukocyte %) should be interpreted as opposed to leukocyte percentage only. 1 Stress Leukogram A stress leukogram is characterized by neutrophilia, lymphopenia, eosinope- nia, and potentially monocytosis.1 It occurs primarily in dogs. The term stress denotes the presence of increased cortisol released from the adrenal gland secondary to severe Top 5 Leukogram Patterns disease (eg, diabetic ketoacidosis, renal failure), high body temperature, pain, dehydra- tion, or hyperadrenocorticism.1 1. Stress Leukogram 2. Inflammatory Leukogram n Neutrophilia occurs because of increased release of mature neutrophils from the bone marrow storage pool to circulating blood and decreased movement of neutro- 3. Persistent Lymphocytosis phils from circulating blood to tissue. (of Mature Lymphocytes) n Lymphopenia results from retention of lymphocytes in lymphoid organs and lym- 4. Neutropenia phocyte lysis. 5. Eosinophilia n Eosinopenia is caused by decreased release of eosinophils from the bone marrow and increased lysis. n Lymphopenia is the hallmark of a stress leukogram. While the degree of neutro- philia may decrease over time, lymphopenia and often eosinopenia will persist as long as plasma concentrations of steroid hormones are increased. n Monocytosis is often found in dogs because of movement of monocytes from the marginating to circulating pool. Monocytosis can be variably found in feline stress leukograms. A stress leukogram may also be seen following administration of exogenous glucocorticoids. A single dose of glucocorticoids may result in a stress leukogram lasting for approximately 24 hours; glucocorticoids administered for longer than 10 days may result in a stress leukogram that persists for 2–3 days after the drug is discontinued.2 The magnitude of the neutrophilia is usually up to twice the upper limit of the normal reference interval. 2 Inflammatory Leukogram An inflammatory leukogram may be characterized by neutrophilia, or in some instances neutropenia, with or without a left shift or toxic change. Inflammatory * At the time of publication, Dr. Schmidt works with IDEXX. At the time of article creation, Dr. mediators result in the release of neutrophils from the bone marrow storage pool to Schmidt was an independent contractor. the circulation, and an increased rate of bone marrow neutrophil production, with or 14 cliniciansbrief.com • May 2015 without the presence of a left shift and neutrophilia vs neutropenia depends on 3 Persistent toxic change. Following stimulation of the balance between neutrophil produc- Lymphocytosis the bone marrow by inflammatory tion and increased tissue demand. (of Mature Lymphocytes) mediators, it takes approximately 2 to 5 As lymphocytes may transiently increase days for maturation and release of Inflammatory diseases include infec- following excitement or exercise second- neutrophils. tious causes (bacterial, fungal, viral, ary to epinephrine, a lymphocytosis protozoal), immune-mediated diseases should be verified by a repeat CBC. A A left shift indicates that immature (immune-mediated hemolytic anemia, review of the blood smear is indicated if (nonsegmented) neutrophils have been polyarthritis), and tissue necrosis. Many the lymphocytosis is persistent, as differ- released from the bone marrow into inflammatory diseases result in a neu- entials will be dependent on lymphocyte circulation prior to maturation to seg- trophilia that is 2 to 10 times the upper morphology (small, mature lymphocytes mented cells. limit of the normal reference interval. vs lymphoblasts) (Figures 2 and 3). Toxic change includes Dohle bodies Other diseases in which the infection is Persistently increased numbers of small (pale blue irregularly shaped cytoplas- isolated, such as a walled-off abscess, to intermediate lymphocytes with con- mic inclusions), increased cytoplasmic may result in a marked neutrophilia densed (mature) chromatin can be the basophilia, and foamy/vacuolated cyto- because production and release from result of a neoplastic lymphocytosis or a plasm. Toxic change indicates acceler- bone marrow is high but tissue con- nonneoplastic lymphocytosis. ated production of neutrophils by the sumption of circulating neutrophils is bone marrow (Figure 1). low as the cells cannot easily infiltrate Chronic lymphocytic leukemia (CLL) is a the lesion.1 type of neoplastic lymphocytosis in which In general, as the left shift or degree of lymphocytes appear small to intermedi- toxic change increases, so does the After the source of the inflammation is ate in size and have condensed chroma- severity of the underlying inflammatory removed (eg, infected uterus), neutro- tin. The absolute lymphocyte count for process. philia may persist for 2–5 days because CLL can be vary between 6000/µL and earlier stimulated neutrophil precursors 8000/µL in dogs and cats, respectively, While neutrophils are emerging from will continue with maturation and the to greater than 150,000/µL.3 the bone marrow, circulating neutro- source of tissue consumption no longer phils are migrating to the source of the exists. Lymphocyte counts greater than inflammation. The presence of a 20,000–30,000/µL are generally more A toxic band neutrophil is found at The majority of the leukocytes are The leukocytes are blast cells, most 1 the top of the image above a toxic 2 small lymphocytes with condensed 3 suggestive of lymphoblasts. The segmented neutrophil. Both cells chromatin. A vacuolated monocyte cells are approximately 12–15 µm have increased cytoplasmic basophilia and is present at the top left of the image. Two in diameter with immature chromatin and foamy cytoplasm. (Modified Wright’s stain, broken cells are present at the right side of the variably distinct nucleoli. (Modified Wright’s 50× original magnification) image. (Modified Wright’s stain, 50× original stain, 50× original magnification) magnification) CLL = chronic lymphocytic leukemia, WBC = white blood cell continues May 2015 • Clinician’s Brief 15 TOP 5 worrisome for CLL than for nonneoplas- endotoxemia, as well as feline leukemia lack of anemia or thrombocytopenia is tic conditions, although some overlap virus infections that can damage hemato- strongly considered with eosinophil may occur. poietic precursor cells and lead to second- counts greater than 20,000 µL. ary infections that consume circulating Causes for nonneoplastic lymphocytosis neutrophils.4,5 Conclusion include diseases that result in immune Evaluation of the leukogram pattern stimulation, including Ehrlichia canis 5 Eosinophilia can aid in formulating differential infections in dogs, feline leukemia/feline Increased bone marrow pro- diagnoses. n cb immunodeficiency virus infection in duction of eosinophils is most com- cats, and Mycoplasma felis infection in monly the result of parasite antigens or References cats.2,3 allergens. Parasites commonly associ- 1. Interpretation of leukocyte responses in disease. Weiser G. In Thrall MA (ed): Veterinary ated with eosinophilia are those found Hematology and Clinical Chemistry—Ames: Thymoma and hypoadrenocorticism are within tissues including Dirofilaria Blackwell, 2006, pp 135-148. differentials for dogs and cats. Hyper- immitis, Aelurostrongylus abstrusus, 2. Interpretation of canine leukocyte responses. Valenciano AC, Decker LS, Cowell thyroidism and immune-mediated Toxocara spp, Toxascaris leonina, Ancy- RL. In Weiss DJ, Wardrop KJ (eds): Schalm’s Vet- hemolytic anemia are additional differ- lostoma caninum, A braziliense, A tubae- erinary Hematology, 6th ed.—Ames: Blackwell, entials for cats. Flow cytometry of a forme, and Uncinaria stenocephala. 2010, pp 321-335. 3. Determining the significance of the per- fresh blood sample (ideally within 2 Blood cell parasites, including Myco- sistent lymphocytosis. Avery AC, Avery PR. days) can greatly aid in determining a plasma spp, Babesia spp, and Cytauxzoon Vet Clin North Am Small Anim Pract 37:267-282, neoplastic lymphocytosis from a non- spp, do not typically result in an eosino- 20 07. neoplastic lymphocytosis. The presence philia. Hypersensitivity reactions sec- 4. Neutropenia in dogs and cats: Causes and consequences. Schnelle AN, Barger AM. Vet of blast cells should be reviewed by a ondary to cutaneous allergens such as Clin North Am Small Anim Pract 42:111-122, clinical pathologist. flea saliva are commonly associated 2012. with eosinophilia, whereas hypersensi- 5. Neutropenia in dogs and cats: A retro- spective study of 261 cases. Brown MR, 4 Neutropenia tivity reactions to inhaled allergens Rogers KS. JAAHA 37:131-139, 2001. Neutropenia can be caused by (atopic dermatitis) are generally not.6 6. Diseases associated with pronounced increased consumption of recently eosinophilia: A study of 105 dogs in Sweden. Lillihöök I, Gunnarsson L, Zakrisoon
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