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blood cell lifespan, 7 probably because canine erythrocytes maintain antioxidant defenses in CKD. 8 A considerable proportion of people with CKD are resistant to erythropoiesis-stimulating agents. 5 This resistance is probably the result of

Open access
in American Journal of Veterinary Research

Abstract

Objective—To investigate the clinicopathologic patterns of the erythropoietic response after renal transplantation in cats with chronic renal failure (CRF).

Animals—14 cats with CRF undergoing renal transplantation.

Procedure—Before and at intervals during a 6-month period after transplantation, serum creatinine and erythropoietin concentrations, Hct, erythrocyte indices, aggregate reticulocyte percentage, and iron variables were measured. Additionally, the number of transfusions administered to and any complications that developed in each cat were recorded.

Results—In all cats, preoperative azotemia resolved within 6 days after renal transplantation. Two cats had a temporary increase in serum creatinine concentration secondary to an acute graft rejection episode. Anemia (defined as Hct < 28%) resolved in 10 cats 3 to 49 days after surgery. Resolution of anemia was delayed in 2 cats that had acute rejection episodes. Serum erythropoietin concentration and reticulocyte percentage were low preoperatively; values after surgery were highly variable. Compared with preoperative values, serum erythropoietin concentration increased 1 to 4 days after surgery in 11 cats; between days 5 and 58, another increase was detected in 9 cats. Serum iron concentrations were generally low before and 14 days after transplantation.

Conclusion and Clinical Relevance—The erythropoietic response was highly variable in cats after renal transplantation, but anemia typically resolved within 1 month after surgery. A delay in resolution of anemia in cats may indicate poor graft function and inadequate iron stores, suggesting the need for further evaluation for concurrent illness. (Am J Vet Res 2003;64: 1248–1254)

Full access
in American Journal of Veterinary Research

lack of peripheral erythrocyte targeting in many cases but does not differentiate dogs with and without evidence of immune-mediated hemolysis (eg, dogs with preregenerative IMHA vs dogs with impaired erythropoiesis). Comparisons among affected dogs

Full access
in Journal of the American Veterinary Medical Association

Summary

Changes in platelet indices (platelet count and platelet size) and pcv associated with thyroid disease were studied in 7 dogs with hypothyroidism and 21 cats with hyperthyroidism that were admitted to the veterinary teaching hospital. Compared with control (euthyroid) dogs, dogs with hypothyroidism had higher platelet count (P = 0.003), smaller platelet size (P = 0.01), and lower pcv (P = 0.02). Comparison of the group of hyperthyroid cats with a group of similarly aged, clinically normal cats with normal thyroxine values indicated that the group of hyperthyroid cats had significantly (P = 0.03) higher mean platelet size than did control cats, but differences were not found in mean platelet count or pcv. Results of this investigation indicate that the changes in platelet size reported in human beings with thyroid endocrinopathies also are found in animals so-affected. Although the pathogenesis of platelet abnormalities in animals with thyroid derangement is unclear and likely is multifactorial, the observed relation between platelet and erythrocyte production in this group of dogs is consistent with reports of an inverse relation between thrombocytopoiesis and erythropoiesis in iatrogenically hyperthyroid mice and in mice exposed to hypoxia.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine the activity of recombinant feline erythropoietin (rfEPO) in murine bioassays and evaluate its efficacy and safety in cats with erythropoietin-dependent nonregenerative anemia.

Animals—26 cats (group 1, 19 cats with anemia attributed to chronic kidney disease [CKD]; group 2, 7 cats with CKD and recombinant human erythropoietin [rhEPO]-induced red cell aplasia [RCA]).

Procedure—The rfEPO was synthesized by use of Chinese hamster ovary (CHO) cells transfected with feline erythropoietin complementary DNA. Preclinical assessments of rfEPO included an erythroid cell proliferation assay and measurements of reticulocytosis in Balb/C mice. Clinical assessments of cats included hematologic, biochemical, and clinical examinations during 12 (group 1) or 6 (group 2) months of rfEPO treatment.

Results—Biological activity of rfEPO was broadly equivalent to rhEPO in preclinical murine bioassays. Median Hct and absolute reticulocyte count in cats increased significantly during the first 3 weeks of rfEPO treatment, and median Hct generally could be maintained within a target range of 30% to 40% with periodic adjustments of rfEPO doses. Unexpectedly, 5 cats in group 1 and 3 cats in group 2 that initially responded to rfEPO treatment again developed anemia that was refractory to additional rfEPO treatments, even at higher doses.

Conclusions and Clinical Relevance—Treatment with rfEPO can reestablish active erythropoiesis in most cats with CKD, even those with anemia attributable to rhEPO-induced RCA. Unfortunately, development of RCA during treatment with CHO cell-derived recombinant erythropoietin proteins was not eliminated as a serious safety concern, even for this feline-specific preparation. (Am J Vet Res 2004;65:1355–1366)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To examine clinical features, laboratory test results, treatment, and outcome of dogs with pure red cell aplasia (PRCA) and idiopathic nonregenerative immune-mediated anemia (NRIMA).

Design—Retrospective study.

Animals—43 dogs with severe nonregenerative anemia.

Procedure—Medical records of dogs determined to have PRCA, NRIMA, or ineffective erythropoiesis on the basis of bone marrow analysis between 1988 and 1999 were reviewed. Criteria for inclusion were ≥ 5- day history of severe nonregenerative anemia (Hct < 20%; < 60.0 X 103 reticulocytes/µl) with no underlying diseases. Information was retrieved on signalment, clinical signs, laboratory test results, treatment, and outcome.

Results—Median age of the dogs was 6.5 years. Spayed females and Labrador Retrievers were significantly overrepresented. Median Hct was 11% with no evidence of regeneration (median, 1.5 X 103 reticulocytes/ µl). Direct Coombs' test results were positive in 57% of dogs. Biochemical abnormalities included hyperferremia and high percentage saturation of transferrin. Bone marrow findings ranged from PRCA (5%) to erythroid hyperplasia (55%). Myelofibrosis was common. Dogs were treated with immunosuppressive drugs and the response was complete, partial, and poor in 55, 18, and 27% of the dogs, respectively. Mortality rate was 28%.

Conclusion and Clinical Relevance—An immunemediated pathogenesis should be considered in dogs with severe, nonregenerative anemia, normal WBC and platelet counts, hyperferremia, mild clinical signs, and no evidence of underlying disease. Bone marrow findings range from the rare PRCA to erythroid hyperplasia. Myelofibrosis is often detected in affected dogs and may prevent bone marrow aspiration. (J Am Vet Med Assoc 2000;216:1429–1436)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective

To determine whether recombinant canine erythropoietin (rcEPO) stimulates erythropoiesis in dogs without causing the immunogenicity problem (ie, erythroid hypoplasia) associated with recombinant human erythropoietin (rhEPO).

Animals

13 clinically normal dogs.

Procedure

Dogs were randomly assigned to 2 groups; 1 group (n = 6) received rhEPO, whereas the other group (7) received rcEPO. Both groups received SC injections of diluent for 4 weeks before initiating treatment with erythropoietin (100 U/kg of body weight, SC, 3 times/wk). Hematocrit and absolute reticulocyte count were monitored weekly, CBC were done monthly, and bone marrow aspirates for cytologic evaluation were obtained before and at 4, 8, 16, and 24 weeks during treatment.

Results

Weekly mean Hct and absolute reticulocyte count increased in both groups of dogs during the first 2 weeks of treatment. For dogs receiving rhEPO, precipitous decreases in reticulocyte number and more gradual decreases in Hct were associated with development of erythroid hypoplasia. Dogs receiving rhEPO developed erythroid hypoplasia by week 4 (n = 4), 8 (1), or 16 (1). With cessation of rhEPO treatment after diagnosis of erythroid hypoplasia, RBC production recovered 5 to 11 weeks (median, 7 weeks) later. In contrast, rcEPO treatment caused sustained increases in Hct and reticulocytosis. None of the dogs receiving rcEPO developed erythroid hypoplasia.

Conclusions

rcEPO stimulated erythrocyte production in clinically normal dogs during a 24-week period without causing the erythroid hypoplasia encountered in rhEPO-treated dogs.

Clinical Relevance

Because rcEPO did not cause erythroid hypoplasia, rcEPO may represent an improved option, compared with rhEPO, for treatment of erythropoietin-dependent anemia in dogs. (Am J Vet Res 1999;60:636–642)

Free access
in American Journal of Veterinary Research

likely explanation for the changes observed. Nonregenerative immune-mediated anemia can be caused by antibody-mediated inhibition of erythropoiesis or destruction of late-stage erythroid precursors (precursor-directed immune-mediated anemia). 1 Because

Full access
in Journal of the American Veterinary Medical Association

I ron is an essential mineral that is critical to many physiological processes including oxygen transport, DNA synthesis, and energy production. 1 It is also a critical component for erythropoiesis, particularly in the development of

Open access
in American Journal of Veterinary Research

procedure and an increased rate of erythropoiesis was evident on the basis of CBC findings (ie, a detectable increase in reticulocyte count [reference range, 1% to 2.3%], an increase in MCV [reference range, 117 to 137 fL], and presence of ≥ 2 nucleated RBCs

Full access
in Journal of the American Veterinary Medical Association