Effects of lithium carbonate on carboplatin-induced thrombocytopenia in dogs

Amélie Leclerc Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

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Anthony C. G. Abrams-Ogg Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

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Stephen A. Kruth Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

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Dorothee Bienzle Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

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Abstract

Objective—To describe the effects of lithium carbonate on thrombopoiesis in clinically normal dogs and in dogs treated with carboplatin.

Animals—18 young adult sexually intact female Beagles.

Procedures—Dogs were assigned to each of 3 treatment groups (6 dogs/group). Group 1 received 150 mg of lithium carbonate (14 to 16 mg/kg), PO, every 12 hours on days 1 through 21. Group 2 received carboplatin (300 mg/m2, IV) on day 0 and cephalexin (30 mg/kg, PO, q 12 h) on days 14 through 21. Group 3 received lithium, carboplatin, and cephalexin at the aforementioned doses and schedules. Plasma lithium and blood platelet concentrations were measured on days 0, 2, 4, 7, 9, 11, 14, 16, 18, and 21. Number of megakaryocytes in bone marrow specimens and the percentage of large unstained cells and CD34+ mononuclear cells in bone marrow aspirates were determined on days 0, 7, 14, and 21 by manual enumeration, automated hematologic analysis, and flow cytometric immunophenotyping, respectively.

Results—Plasma lithium concentrations ranged from 0.12 to 2.41 mmol/L. All dogs given lithium achieved a concentration within the target interval of 0.5 to 1.5 mmol/L by days 4 to 7. Thrombopoiesis was increased in dogs receiving lithium alone. All dogs given carboplatin developed mild thrombocytopenia. There were no differences between group 2 and group 3 throughout the study.

Conclusions and Clinical Relevance—Lithium stimulated thrombopoiesis in clinically normal dogs. Lithium administration at the doses and schedules used, with concurrent administration of cephalexin, did not prevent thrombocytopenia induced by carboplatin.

Abstract

Objective—To describe the effects of lithium carbonate on thrombopoiesis in clinically normal dogs and in dogs treated with carboplatin.

Animals—18 young adult sexually intact female Beagles.

Procedures—Dogs were assigned to each of 3 treatment groups (6 dogs/group). Group 1 received 150 mg of lithium carbonate (14 to 16 mg/kg), PO, every 12 hours on days 1 through 21. Group 2 received carboplatin (300 mg/m2, IV) on day 0 and cephalexin (30 mg/kg, PO, q 12 h) on days 14 through 21. Group 3 received lithium, carboplatin, and cephalexin at the aforementioned doses and schedules. Plasma lithium and blood platelet concentrations were measured on days 0, 2, 4, 7, 9, 11, 14, 16, 18, and 21. Number of megakaryocytes in bone marrow specimens and the percentage of large unstained cells and CD34+ mononuclear cells in bone marrow aspirates were determined on days 0, 7, 14, and 21 by manual enumeration, automated hematologic analysis, and flow cytometric immunophenotyping, respectively.

Results—Plasma lithium concentrations ranged from 0.12 to 2.41 mmol/L. All dogs given lithium achieved a concentration within the target interval of 0.5 to 1.5 mmol/L by days 4 to 7. Thrombopoiesis was increased in dogs receiving lithium alone. All dogs given carboplatin developed mild thrombocytopenia. There were no differences between group 2 and group 3 throughout the study.

Conclusions and Clinical Relevance—Lithium stimulated thrombopoiesis in clinically normal dogs. Lithium administration at the doses and schedules used, with concurrent administration of cephalexin, did not prevent thrombocytopenia induced by carboplatin.

Contributor Notes

Dr. Leclerc's present address is Royal Canin Canada, 100 Beiber Rd, Rural Rte No. 3, Guelph, ON N1H 6H9, Canada.

Supported by the Ontario Veterinary College Pet Trust.

Presented in part as an oral presentation at the 22nd Annual American College of Veterinary Internal Medicine Forum, Minneapolis, June 2004.

The authors thank Gabrielle Monteith and William Sears for assistance with statistical analysis.

Address correspondence to Dr. Abrams-Ogg (aogg@uoguelph.ca).
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