CLINICAL PATHOLOGY PATHOLOGIE CLINIQUE Clinical pathology interpretation Barbara Horney History, physical examination, and Table 1. Hematologic findings from a lethargic, laboratory findings 4-year-old schipperke 4-year-old, spayed female, schipperke was pre- Blood cell count Reference range A sented because of mild lethargy. Pale mucous mem- White blood cells branes were observed on physical examination. Table 1 (WBC) gives the results of the hematological examination of Total 6.0 X 109/L 6.0-17.1 X 109/L blood at Differential samples taken this time. No significant abnor- segmented 65% 3.85 X 109/L 3.6-11.5 X 109/L malities were identified on the serum biochemical neutrophils profile. eosinophils 2% 0.12 X 109/L 0.01-1.25 X 109/L lymphocytes 27% 1.59 X 109/L 1.0-4.8 X 109/L Interpretation and discussion monocytes 6% 0.35 X 109/L 0.15-1.35 X 109/L Red blood cells The hematology results can be summarized as severe, Total 1.2 X 1012/L 5.5-8.5 X 109/L microcytic, normochromic, nonregenerative anemia nucleated 1/100 WBC <1-2 per 100 WBC associated with marked spherocytosis. spherocytes 4+ microcytosis 2+ The presence of spherocytes is often associated with immune-mediated hemolytic disease [1,2], although Platelets estimated normal hereditary membrane defects [3] and zinc toxicosis [4] in number can also result in spherocyte formation. A direct antibody Reticulocytes 0 X 109/L up to 120 X 109/L test (Coomb's test) was weakly positive. This finding can Hemoglobin 22 g/L 120-180 g/L support the tentative diagnosis of anemia of immune- Hematocrit 0.068 L/L 0.37-0.55 L/L mediated etiology, although this test is subject to both Mean corpuscular false positive and false negative results [2,5]. The clas- volume 56.3 fL 60-77 fL sification of this dog' s anemia as nonregenerative was Mean corpuscular 18.3 pg 19.5-24.5 pg based on the absence of reticulocytes in the peripheral hemoglobin blood. The absence of both polychromatophils and Mean corpuscular 326 g/L 320-360 g/L macrocytic red blood cells (RBC) supports this classi- hemoglobin fication. The microcytosis is likely a result of the promi- concentration nent spherocytosis. Although immune-mediated ane- mia is classically reported to be associated with a regenerative response, often marked in degree [5], the blood is sampled prior to the appearance of immature absence of a regenerative response should not be used to RBCs subsequent to an acute red cell loss (hemorrhage eliminate immune mechanisms as a cause for anemia or hemolysis). It takes a minimum of 3 d for reticulocytes (6-8). In fact, in 2 studies, a lack of reticulocytosis in to appear in the peripheral blood as a result of stimula- association with canine immune-mediated anemia was tion of RBC production following an acute blood loss found in 23% and 53% of the cases studied (9,10). and response does not peak until 7 d following blood A lack of evidence of RBC regeneration in peripheral loss (11). blood in the face of anemia may be due to an abnormality Explanations for a nonregenerative peripheral erythron in the ability of the marrow to produce and release in immune-mediated anemia include 1) sampling after RBCs, which may include abnormalities in stimula- an acute hemolytic event and prior to the appearance of tion of erythroid production (erythropoietin deficiency), a peripheral response, or 2) immune-mediated destruc- lack of stem cell input (aplasia or hypoplasia), or lack of tion of RBC precursors in the bone marrow stages maturation and release of reticulocytes (ineffective ery- before they appear in the circulating pool (7,8). thropoiesis). Reticulocytosis is also absent if peripheral Examination of bone marrow may help to demonstrate ineffective erythropoiesis, which is characterized by the increase in erythroid precursors with evidence of Atlantic Veterinary College, University of Prince Edward maturation arrest (cells of immature stages predomi- Island, 550 University Avenue, Charlottetown, Prince Edward nate and few cells of later stages are present) (7). Island C1A 4P3. Reports of immune-mediated anemia associated with Can Vot J Volume 39, March 1998 177 red cell aplasia (absence of RBC precursors in the bone 3. Inaba M, Yawata A, Koshino I, et al. Defective anion transport and marrow) indicate that RBC production can be affected marked spherocytosis with membrane instability caused by hered- at very itary total deficiency of red cell band 3 in cattle due to a nonsense immature cell stages in some cases [6,8]. mutation. J Clin Invest 1996; 97: 1804-1817. The relatively mild clinical signs demonstrated by this 4. Latimer KS, Jain AV, Inglesby HB, Clarkson WD, Johnson GB. dog in association with such a profound anemia indicated Zinc-induced hemolytic anemia caused by ingestion of pennies by that the anemia was the result of a more prolonged a pup. J Am Vet Med Assoc 1989; 195: 77-80. process with sufficient time to allow physiologic com- 5. Cotter SM. Autoimmune hemolytic anemia in dogs. Compend Contin Educ Pract Vet 1992; 14: 53-59. pensatory mechanisms to develop. Examination of bone 6. Weiss DJ. Antibody-mediated suppression of erythropoiesis in dogs marrow aspirate in this case showed increased marrow with red blood cell aplasia. Am J Vet Res 1986; 47: 2646-2648. cellularity characterized by increased erythroid cell 7. Jonas LD, Thrall MA, Weiser MG. Nonregenerative form of proliferation, with a large number of prorubricytes and immune-mediated hemolytic anemia in dogs. J Am Anim Hosp rubricytes but few metarubricytes and Assoc 1987; 23: 201-203. polychromatophils 8. Scott-Moncrieff JCR, Reagan WJR, Glickman LT, DeNicola (ineffective erythropoiesis). Appropriate immunosup- DB, Harrington D. Treatment of nonregenerative anemia with pressive therapy was initiated and reticulocytes (11.5 X human g-globulin in dogs. J Am Vet Med Assoc 1995; 206: 109/L) appeared in the peripheral blood of this dog 4 d 1895-1900. later. An absolute reticulocytosis (>120 reticulocytes X 9. Klag AR, Giger U, Shofer FS. Idiopathic immune-mediated hemolytic anemia in dogs: 42 cases (1986-1990). J Am Vet Med 109/L) was not observed until day 8. Resolution of the Assoc 1993; 202: 783-788. anemia in this dog occurred slowly and the immuno- 10. Feldman BF. Demographics of canine immune-mediated suppressive medication was reduced gradually over haemolytic anaemia in the southeastern United States. Comp several months. Haematol Int 1996; 6: 42-45. 11. Jain NC. Schalm's Veterinary Hematology, 4th ed. Philadelphia: References Lea & Febiger, 1986: 564, 578-581. 1. Tyler RD, Cowell RL. Classification and diagnosis of anaemia. Comp Haematol Int 1996; 6: 1-16. 2. Stewart AF, Feldman BF. Immune-mediated haemolytic anemia. Part II. Clinical entity, diagnosis, and treatment theory. Compend Contin Educ Pract Vet 1993; 15: 1479-1491. Through the generosity ofseveral book publishers, the Canadian Grace a la generosit6 d'un grand nombre d'Wditeurs, la Revue Veterinary Journal is able to inform readers ofnew publications vet&rinaire canadienne est en mesure de tenir ses lecteurs au that are now available to veterinary practitioners. Readers are courant des nouvelles publications rendues disponibles aux invited to contact their local library, the publishers listed here, or m6decins vet6rinaires. On encourage les lecteurs qui desirent the bookstores of Canadian veterinary colleges should they wish obtenir une de ces publications a entrer en contact avec leur to obtain their own copies. bibliotheque, avec les dditeurs listes ci-bas ou avec les librairies aux facultes de m6decine v6t6rinaire. * Pastoret P-P, Blancou J, Vannier P, Verschueren C, * Pratt PW, ed. Mosby's Review: Questions and eds. Veterinary Vaccinology. Elsevier Science, Answersfor Veterinary Boards: Ancillary Topics, Amsterdam, The Netherlands, 1997. 882 pp. ISBN 2nd ed. Mosby, Toronto, 1998. 302 pp. ISBN 0-444-81968-1. $200.75 US 0-8151-7466-7. $55.95 * Pratt PW, ed. Mosby's Review: Questions and * Pratt PW, ed. Mosby's Review: Questions and Answers for Veterinary Boards: Large Animal Answers for Veterinary Boards: Clinical Sciences, Medicine and Surgery, 2nd ed. Mosby, Toronto, 2nd ed. Mosby, Toronto, 1998. 273 pp. ISBN 1998. 299 pp. ISBN 0-8151-7466-7. $55.95 0-8151-7466-7. $55.95 * Pratt PW, ed. Mosby's Review: Questions and * Pratt PW, ed. Mosby's Review: Questions and Answers for Veterinary Boards: Small Animal Answers for Veterinary Boards: Basic Sciences, Medicine and Surgery, 2nd ed. Mosby, Toronto, 2nd ed. Mosby, Toronto, 1998. 274 pp. ISBN 1998. 313 pp. ISBN 0-8151-7465-9. $55.95 0-8151-7466-7. $55.95 178 Can Vet J Volume 39, March 1998.