• 1.

    Demetri GD. Targeted approaches for the treatment of thrombocytopenia. Oncologist 2001;6(suppl 5):1523.

  • 2.

    Rassnick KM, Mauldin GE, Al-Sarraf R, et alMOPP chemotherapy for treatment of resistant lymphoma in dogs: a retrospective study of 117 cases (1989–2000). J Vet Intern Med 2002;16:576580.

    • Search Google Scholar
    • Export Citation
  • 3.

    Moore AS, London CA, Wood CA, et alLomustine (CCNU) for the treatment of resistant lymphoma in dogs. J Vet Intern Med 1999;13:395398.

  • 4.

    Page RL, McEntee MC, George SL, et alPharmacokinetic and phase I evaluation of carboplatin in dogs. J Vet Intern Med 1993;7:235240.

  • 5.

    Cepeda V, Fuertes MA, Castilla J, et alBiochemical mechanisms of cisplatin cytotoxicity. Anticancer Agents Med Chem 2007;7:318.

  • 6.

    Bergman PJ, MacEwen EG, Kurzman ID, et alAmputation and carboplatin for treatment of dogs with osteosarcoma: 48 cases (1991 to 1993). J Vet Intern Med 1996;10:7681.

    • Search Google Scholar
    • Export Citation
  • 7.

    Chun R, Knapp DW, Widmer WR, et alPhase II clinical trial of carboplatin in canine transitional cell carcinoma of the urinary bladder. J Vet Intern Med 1997;11:279283.

    • Search Google Scholar
    • Export Citation
  • 8.

    Rassnick KM, Ruslander DM, Cotter SM, et alUse of carboplatin for treatment of dogs with malignant melanoma: 27 cases (1989–2000). J Am Vet Med Assoc 2001;218:14441448.

    • Search Google Scholar
    • Export Citation
  • 9.

    Abrams-Ogg AC. Triggers for prophylactic use of platelet transfusions and optimal platelet dosing in thrombocytopenic dogs and cats. Vet Clin North Am Small Anim Pract 2003;33:14011418.

    • Search Google Scholar
    • Export Citation
  • 10.

    Kuter DJ. New thrombopoietic growth factors. Blood 2007;109:46074616.

  • 11.

    Ault P, Kantarjian H, Welch MA, et alInterleukin 11 may improve thrombocytopenia associated with imatinib mesylate therapy in chronic myelogenous leukemia. Leuk Res 2004;28:613618.

    • Search Google Scholar
    • Export Citation
  • 12.

    Nash RA, Seidel K, Storb R, et alEffects of rhIL-11 on normal dogs and after sublethal radiation. Exp Hematol 1995;23:389396.

  • 13.

    Olsen EH, McCain AS, Merricks EP, et alComparative response of plasma VWF in dogs to up-regulation of VWF mRNA by interleukin-11 versus Weibel-Palade body release by desmopressin (DDAVP). Blood 2003;102:436441.

    • Search Google Scholar
    • Export Citation
  • 14.

    Reagan WJ, Murphy D, Battaglino M, et alAntibodies to canine granulocyte colony-stimulating factor induce persistent neutropenia. Vet Pathol 1995;32:374378.

    • Search Google Scholar
    • Export Citation
  • 15.

    Randolph JE, Scarlett J, Stokol T, et alClinical efficacy and safety of recombinant canine erythropoietin in dogs with anemia of chronic renal failure and dogs with recombinant human erythropoietin-induced red cell aplasia. J Vet Intern Med 2004;18:8191.

    • Search Google Scholar
    • Export Citation
  • 16.

    Bille PE, Jensen MK, Kaalund-Jensen JP, et alStudies on the haematologic and cytogenetic effect of lithium. Acta Med Scand 1975;198:281286.

    • Search Google Scholar
    • Export Citation
  • 17.

    Joffe RT, Kellner CH, Post RM, et alLithium increases platelet count. N Engl J Med 1984;311:674675.

  • 18.

    Balon R, Berchou R, Lycaki H, et alThe effect of lithium on platelet count. Acta Psychiatr Scand 1986;74:474478.

  • 19.

    Harker WG, Rothstein G, Clarkson D, et alEnhancement of colony-stimulating activity production by lithium. Blood 1977;49:263267.

  • 20.

    Rossof AH, Fehir KM. Lithium carbonate increases marrow granulocyte-committed colony-forming units and peripheral blood granulocytes in a canine model. Exp Hematol 1979;7:255258.

    • Search Google Scholar
    • Export Citation
  • 21.

    Joyce RA, Chevernick PA. The effect of lithium on release of granulocyte colony stimulating activity in vitro. Adv Exp Med Biol 1980;127:7986.

    • Search Google Scholar
    • Export Citation
  • 22.

    Turner AR, Allalunis MJ. Oral lithium carbonate increases colony stimulating activity production from human mononuclear cells. Adv Exp Med Biol 1980;127:127136.

    • Search Google Scholar
    • Export Citation
  • 23.

    Greenberg PL, Packard B, Steed SM. Effects of lithium chloride on human and murine marrow myeloid colony formation and colony stimulating activity. Adv Exp Med Biol 1980;127:137144.

    • Search Google Scholar
    • Export Citation
  • 24.

    Gallicchio VS, Chen MG. Influence of lithium on proliferation of hematopoietic stem cells. Exp Hematol 1981;9:804810.

  • 25.

    Gamba-Vitalo C, Gallicchio VS, Watts TD, et alLithium stimulated in vitro megakaryocytopoiesis. Exp Hematol 1983;11:382388.

  • 26.

    Joyce RA. Sequential effects of lithium on haematopoiesis. Br J Haematol 1984;56:307321.

  • 27.

    Gallicchio VS, Gamba-Vitalo VS, Watts TD, et alIn vivo and in vitro modulation of megakaryocytopoiesis and stromal colony formation by lithium. J Lab Clin Med 1986;108:199205.

    • Search Google Scholar
    • Export Citation
  • 28.

    Boggs DR, Joyce RA. The hematopoietic effects of lithium. Semin Hematol 1983;20:129138.

  • 29.

    Focosi D, Azzarà A, Kast RE, et alLithium and hematology: established and proposed uses. J Leukoc Biol 2009;85:2028.

  • 30.

    Hager ED, Dziambor H, Höhmann D, et alEffects of lithium on thrombopoiesis in patients with low platelet cell counts following chemotherapy or radiotherapy. Biol Trace Elem Res 2001;83:139148.

    • Search Google Scholar
    • Export Citation
  • 31.

    Hammond WP, Dale DC. Lithium therapy of canine cyclic hematopoiesis. Blood 1980;55:2628.

  • 32.

    Hammond WP, Dale DC. Cyclic hematopoiesis: effects of lithium on colony-forming cells and colony-stimulating activity in grey Collie dogs. Blood 1982;59:179184.

    • Search Google Scholar
    • Export Citation
  • 33.

    Murtaugh RJ, Jacobs RM. Suspected immune-mediated megakaryocytic hypoplasia or aplasia in a dog. J Am Vet Med Assoc 1985;186:13131315.

  • 34.

    Rossof AH, Fehir KM, Budd HS, et alLithium carbonate enhances granulopoiesis and attenuates cyclophosphamide-induced injury in the dog. Adv Exp Med Biol 1980;127:155166.

    • Search Google Scholar
    • Export Citation
  • 35.

    Maddux JM, Shaw SE. Possible beneficial effect of lithium therapy in a case of estrogen-induced bone marrow hypoplasia in a dog. J Am Anim Hosp Assoc 1983;19:242245.

    • Search Google Scholar
    • Export Citation
  • 36.

    Hall EJ. Use of lithium for treatment of estrogen-induced bone marrow hypoplasia in a dog. J Am Vet Med Assoc 1992;200:814816.

  • 37.

    Sanpera N, Masot N, Janer M, et alOestrogen-induced bone marrow aplasia in a dog with a Sertoli cell tumour. J Small Anim Pract 2002;43:365369.

    • Search Google Scholar
    • Export Citation
  • 38.

    Case BC, Hauck ML, Yeager RL, et alThe pharmacokinetics and pharmacodynamics of GW395058, a peptide agonist of the thrombopoietin receptor, in the dog, a large-animal model of chemotherapy-induced thrombocytopenia. Stem Cells 2000;18:360365.

    • Search Google Scholar
    • Export Citation
  • 39.

    Bennett WM. Drug interactions and consequences of sodium restriction. Am J Clin Nutr 1997;65:678S681S.

  • 40.

    Olfert ED, Cross BM, McWilliam AA, eds. Guide to the care and use of experimental animals. Vol 1. 2nd ed. Ottawa: Canadian Council on Animal Care, 1993.

    • Search Google Scholar
    • Export Citation
  • 41.

    Olfert ED, Cross BM, McWilliam AA, eds. Guide to the care and use of experimental animals. Vol 2. Ottawa: Canadian Council on Animal Care, 1984.

    • Search Google Scholar
    • Export Citation
  • 42.

    Rosenthal RC, Koritz GD, Davis LE. Pharmacokinetics of lithium in the dog. J Vet Pharmacol Ther 1986;9:8187.

  • 43.

    Zakynthinos SG, Papanikolaou S, Theodoridis T, et alSepsis severity is the major determinant of circulating thrombopoietin levels in septic patients. Crit Care Med 2004;32:10041010.

    • Search Google Scholar
    • Export Citation
  • 44.

    Kletter Y, Singer A, Nagler A, et alCiprofloxacin enhances hematopoiesis and the peritoneal neutrophil function in lethally irradiated, bone marrow-transplanted mice. Exp Hematol 1994;22:360365.

    • Search Google Scholar
    • Export Citation
  • 45.

    Stein RS, Howard CA, Brennan M, et alLithium carbonate and granulocyte production: dose optimization. Cancer 1981;48:26972701.

  • 46.

    Ricci P, Bandini G, Franchi P, et alHaematological effects of lithium carbonate: a study in 56 psychiatric patients. Haematologica 1981;66:627633.

    • Search Google Scholar
    • Export Citation
  • 47.

    Kuwabara T. Effects of lithium on mouse hematopoiesis. Nippon Ika Daigaku Zasshi 1990;57:408415.

  • 48.

    Greenfield HM, Sweeney DA, Newton RK, et alEstimation of haemopoietic progenitor cells in peripheral blood by the Advia 120 and BD vantage flow cytometer: a direct comparison for the prediction of adequate collections. Clin Lab Haematol 2005;27:287291.

    • Search Google Scholar
    • Export Citation
  • 49.

    Bononi A, Lanza F, Dabusti M, et alIncreased myeloperoxidase index and large unstained cell values can predict the neutropenia phase of cancer patients treated with standard dose chemotherapy. Cytometry 2001;46:9297.

    • Search Google Scholar
    • Export Citation
  • 50.

    Kondo M, Wagers AJ, Manz MG, et alBiology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol 2003;21:759806.

    • Search Google Scholar
    • Export Citation
  • 51.

    Ballin A, Lehman D, Sirota P, et alIncreased number of peripheral blood CD34+ cells in lithium-treated patients. Br J Haematol 1998;100:219221.

    • Search Google Scholar
    • Export Citation
  • 52.

    Laughlin MJ, Christiansen NP, Herzig GP, et alCD34 progenitor cell subset analyses in normal human bone marrow and marrow harvested after intermediate-dose chemotherapy. Cytometry 1996;26:235242.

    • Search Google Scholar
    • Export Citation
  • 53.

    Gallicchio VS, Chen MG, Watts TD. Ability of lithium to accelerate the recovery of granulopoiesis after subacute radiation injury. Acta Radiol Oncol 1984;23:361366.

    • Search Google Scholar
    • Export Citation
  • 54.

    Joyce RA, Chervenick PA. Lithium effects on granulopoiesis in mice following cytotoxic chemotherapy. Adv Exp Med Biol 1980;127:145154.

  • 55.

    Gallicchio VS. Lithium and hematopoietic toxicity. I. Recovery in vivo of murine hematopoietic stem cells (CFU-S and CFU-mix) after single-dose administration of cyclophosphamide. Exp Hematol 1986;14:395400.

    • Search Google Scholar
    • Export Citation
  • 56.

    Cass CE, Turner AR, Selner M, et alEffect of lithium on the myelosuppressive and chemotherapeutic activities of vinblastine. Cancer Res 1981;41:10001005.

    • Search Google Scholar
    • Export Citation
  • 57.

    Gallicchio VS. Lithium and hematopoietic toxicity. II. Acceleration in vivo of murine hematopoietic progenitor cells (CFU-gm and CFU-meg) following treatment with vinblastine sulfate. Int J Cell Cloning 1987;5:122133.

    • Search Google Scholar
    • Export Citation
  • 58.

    Gallicchio VS. Lithium and hematopoietic toxicity. III. In vivo recovery of hematopoiesis following single-dose administration of cyclophosphamide. Acta Haematol 1988;79:192197.

    • Search Google Scholar
    • Export Citation
  • 59.

    Catane R, Kaufman J, Mittelman A, et alAttenuation of myelo-suppression with lithium. N Engl J Med 1977;297:452453.

  • 60.

    Stein RS, Beaman C, Ali MY, et alLithium carbonate attenuation of chemotherapy-induced neutropenia. N Engl J Med 1977;297:430431.

  • 61.

    Charron DJ, Schmitt T, Degos L. Therapeutic complications in acute myelogenous leukemia. N Engl J Med 1979;301:557558.

  • 62.

    Lyman GH, Williams CC, Preston D, et alLithium carbonate in patients with small cell lung cancer receiving combination chemotherapy. Am J Med 1981;70:12221229.

    • Search Google Scholar
    • Export Citation
  • 63.

    Bandini G, Ricci P, Ruggero D, et alLithium and granulocytopenia during induction treatment of adult acute lymphoblastic leukemi. Tumori 1982;68:427430.

    • Search Google Scholar
    • Export Citation
  • 64.

    Steinherz PG, Rosen G, Miller DR. Effect of lithium carbonate plus oxymetholone vs. lithium alone on chemotherapy-induced myelosuppression. Am J Pediatr Hematol Oncol 1983;5:3944.

    • Search Google Scholar
    • Export Citation
  • 65.

    Ricevuti G, Mazzone A, Rizzo SC. The effects of lithium on platelet count. Acta Haematol 1985;74:118119.

  • 66.

    Kitada N, Takara K, Itoh C, et alComparative analysis of cell injury after exposure to antitumor platinum derivatives in kidney tubular epithelial cells. Chemotherapy 2008;54:217223.

    • Search Google Scholar
    • Export Citation
  • 67.

    Neupogen [product information], version 20.2. Thousand Oaks, Calif: Amgen Inc, 2007.

  • 68.

    Leukine [product information]. Seattle, Wash: Bayer Health Care Pharmaceuticals LLC, 2008.

  • 69.

    Petros WP, Crawford J. Safety of concomitant use of granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor with cytotoxic chemotherapy agents. Curr Opin Hematol 1997;4:213216.

    • Search Google Scholar
    • Export Citation
  • 70.

    von der Maase H. Interactions of drugs and radiation in haemopoietic tissue assessed by lethality of mice after whole-body irradiation. Int J Radiat Biol Relat Stud Phys Chem Med 1985;48:371380.

    • Search Google Scholar
    • Export Citation
  • 71.

    Radley JM, Barber L, Hodgson GS. Pretreatment with cytosine arabinoside does not protect against the delayed effects of irradiation on thrombopoiesis and erythropoiesis. Exp Hematol 1994;22:587592.

    • Search Google Scholar
    • Export Citation
  • 72.

    Bowen D, Johnson DH, Southerland WM, et al5-fluorouracil simultaneously maintains methotrexate antineoplastic activity in human breast cancer and protects against methotrexate cytotoxicity in human bone marrow. Anticancer Res 1999;19:985988.

    • Search Google Scholar
    • Export Citation
  • 73.

    Hedley DW, McElwain TJ, Millar JL, et alAcceleration of bone-marrow recovery by pre-treatment with cyclophosphamide in patients receiving high-dose melphalan. Lancet 1978;2:966968.

    • Search Google Scholar
    • Export Citation
  • 74.

    Johnke RM, Abernathy RS. Accelerated marrow recovery following total-body irradiation after treatment with vincristine, lithium or combined vincristine-lithium. Int J Cell Cloning 1991;9:7888.

    • Search Google Scholar
    • Export Citation
  • 75.

    Bernstein SH, Fay JP, Christiansen MP, et alSequential interleukin-3 and granulocyte-colony stimulating factor prior to and following high-dose etoposide and cyclophosphamide: a phase I/II trial. Clin Cancer Res 1997;3:15191526.

    • Search Google Scholar
    • Export Citation
  • 76.

    Visca U, Mensi F, Spina MP, et alPrevention by using lithium carbonate of neutropenia due to antiblastics. Adv Exp Med Biol 1980;127:245255.

    • Search Google Scholar
    • Export Citation

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Effects of lithium carbonate on carboplatin-induced thrombocytopenia in dogs

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  • 1 Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
  • | 2 Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
  • | 3 Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
  • | 4 Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

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).