Editorial Type:
Physiology

Effect of leukoreduction treatment on vascular endothelial growth factor concentration in stored canine blood transfusion products

Christine Graf Clinic of Small Animals, Faculty of Veterinary Medicine, Freie Universität Berlin, D-14163 Berlin, Germany.

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Jens Raila Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal (Potsdam-Rehbrücke), Germany.

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Florian J. Schweigert Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal (Potsdam-Rehbrücke), Germany.

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Barbara Kohn Clinic of Small Animals, Faculty of Veterinary Medicine, Freie Universität Berlin, D-14163 Berlin, Germany.

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DOI:
https://doi.org/10.2460/ajvr.73.12.2001
Volume/Issue:
Volume 73: Issue 12
Online Publication Date:
01 Dec 2012
Restricted access
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Abstract

Objective—To evaluate vascular endothelial growth factor (VEGF) concentrations in canine blood products treated with or without a leukoreduction filter.

Sample—10 canine blood donors.

Procedures—Dogs underwent blood collection. Five of 10 units were leukoreduced prior to separation into packed RBCs and fresh frozen plasma (FFP). Concentrations of VEGF were measured by ELISA in plasma supernatants from aliquots of packed RBCs obtained immediately after separation and on days 7, 14, and 21 of storage. Fresh frozen plasma samples of 2 filtered and 2 nonfiltered units were examined after storage.

Results—RBC counts in whole blood before and after leukoreduction did not differ significantly, but WBCs and platelets were removed effectively. The VEGF concentration was lower than the detection limit (9 pg/mL) in 9 of 10 plasma samples and in all packed RBC and FFP units immediately after separation. The median VEGF concentrations in 5 nonfiltered packed RBC units were 37, 164, and 110 pg/mL on days 7, 14, and 21 of storage, respectively. In 5 filtered packed RBC and all FFP units, VEGF concentrations remained lower than the detection limit.

Conclusions and Clinical Relevance—Leukoreduction filters were effective in preventing the release of VEGF during storage of canine RBC products.

Abstract

Objective—To evaluate vascular endothelial growth factor (VEGF) concentrations in canine blood products treated with or without a leukoreduction filter.

Sample—10 canine blood donors.

Procedures—Dogs underwent blood collection. Five of 10 units were leukoreduced prior to separation into packed RBCs and fresh frozen plasma (FFP). Concentrations of VEGF were measured by ELISA in plasma supernatants from aliquots of packed RBCs obtained immediately after separation and on days 7, 14, and 21 of storage. Fresh frozen plasma samples of 2 filtered and 2 nonfiltered units were examined after storage.

Results—RBC counts in whole blood before and after leukoreduction did not differ significantly, but WBCs and platelets were removed effectively. The VEGF concentration was lower than the detection limit (9 pg/mL) in 9 of 10 plasma samples and in all packed RBC and FFP units immediately after separation. The median VEGF concentrations in 5 nonfiltered packed RBC units were 37, 164, and 110 pg/mL on days 7, 14, and 21 of storage, respectively. In 5 filtered packed RBC and all FFP units, VEGF concentrations remained lower than the detection limit.

Conclusions and Clinical Relevance—Leukoreduction filters were effective in preventing the release of VEGF during storage of canine RBC products.

Contributor Notes

This manuscript represents a portion of a thesis submitted by Dr. Graf to the Faculty of Veterinary Medicine, Freie Universität Berlin, as partial fulfillment of the requirements for the doctoral thesis.

Presented in abstract form at the 17th Annual Congress of the Deutsche Veterinärmedizinische Gesellschaft Fachgruppe Innere Medizin und klinische Labordiagnostik, Berlin, January 2009, and in poster form at the 19th Congress of the European College of Veterinary Internal Medicine, Porto, Portugal, September 2009.

Address correspondence to Dr. Kohn (kohn@vetmed.fu-berlin.de).
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Dec 2012

  • 1. Seghezzi G, Patel S, Ren CJ, et alFibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: an autocrine mechanism contributing to angiogenesis. J Cell Biol 1998;141:1659–1673.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 2. Dvorak HF, Sioussat TM, Brown LF, et alDistribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels. J Exp Med 1991;174:1275–1278.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 3. Restucci B, Papparella S, Maiolino P, et alExpression of vascular endothelial growth factor in canine mammary tumors. Vet Pathol 2002;39:488–493.

  • 4. Banks RE, Forbes MA, Kinsey SE, et alRelease of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology. Br J Cancer 1998;77:956–964.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 5. Gaudry M, Bregerie O, Andrieu V, et alIntracellular pool of vascular endothelial growth factor in human neutrophils. Blood 1997;90:4153–4161.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 6. Ferrara N, Carver-Moore K, Chen H, et alHeterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996;380:439–442.

  • 7. Brown LF, Yeo KT, Berse B, et alExpression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med 1992;176:1375–1379.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 8. Maniwa Y, Okada M, Ishii N, et alVascular endothelial growth factor increased by pulmonary surgery accelerates the growth of micrometastases in metastatic lung cancer. Chest 1998;114:1668–1675.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 9. Wynendaele W, Derua R, Hoylaerts MF, et alVascular endothelial growth factor measured in platelet poor plasma allows optimal separation between cancer patients and volunteers: a key to study an angiogenic marker in vivo? Ann Oncol 1999;10:965–971.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 10. Troy GC, Huckle WR, Rossmeisl JH, et alEndostatin and vascular endothelial growth factor concentrations in healthy dogs, dogs with selected neoplasia, and dogs with nonneoplastic diseases. J Vet Intern Med 2006;20:144–150.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 11. Edvardsen L, Nielsen HI, Pedersen AN, et alLeucocyte and platelet derived bioactive substances in stored standard platelet concentrates. Eur J Haematol 1996;57:185–187.

    • Search Google Scholar
    • Export Citation

  • 12. Frewin DB, Jonsson JR, Head RJ, et alHistamine levels in stored human blood. Transfusion 1984;24:502–504.

  • 13. Nielsen HJ. Clinical impact of bioactive substances in blood components. Implications for leucocyte filtration. Infusionsther Transfusionsmed 1998;25:296–304.

    • Search Google Scholar
    • Export Citation

  • 14. Nielsen HJ, Reimert CM, Pedersen AN, et alTime-dependent, spontaneous release of white cell- and platelet-derived bioactive substances from stored human blood. Transfusion 1996;36:960–965.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 15. Reid TJ, Esteban G, Clear M, et alPlatelet membrane integrity during storage and activation. Transfusion 1999;39:616–624.

  • 16. Stack G, Baril L, Napychank P, et alCytokine generation in stored, white cell-reduced, and bacterially contaminated units of red cells. Transfusion 1995;35:199–203.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 17. Stack G, Snyder EL. Cytokine generation in stored platelet concentrates. Transfusion 1994;34:20–25.

  • 18. Blumberg N, Heal JM. Immunomodulation by blood transfusion. An evolving scientific and clinical challenge. Am J Med 1996;101:299–308.

  • 19. Brand A. Leukocyte-poor blood: arguments and guidelines. Vox Sang 1994;67(suppl 3):129–131.

  • 20. Miller JP, Mintz PD. The use of leukocyte-reduced blood components. Hematol Oncol Clin North Am 1995;9:69–90.

  • 21. Nielsen HJ, Werther K, Mynster T, et alSoluble vascular endothelial growth factor in various blood transfusion components. Transfusion 1999;39:1078–1083.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 22. Werther K, Christensen IJ, Nielsen HJ. The association between preoperative concentration of soluble vascular endothelial growth factor, perioperative blood transfusion, and survival in patients with primary colorectal cancer. Eur J Surg 2001;167:287–292.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 23. Slichter SJ, Fish D, Abrams VK, et alEvaluation of different methods of leukoreduction of donor platelets to prevent alloimmune platelet refractoriness and induce tolerance in a canine transfusion model. Blood 2005;105:847–854.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 24. Brownlee L, Wardrop KJ, Sellon RK, et alUse of a prestorage leukoreduction filter effectively removes leukocytes from canine whole blood while preserving red blood cell viability. J Vet Intern Med 2000;14:412–417.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 25. McMichael MA, Smith SA, Galligan A, et alEffect of leukoreduction on transfusion-induced inflammation in dogs. J Vet Intern Med 2010;24:1131–1137.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 26. Kohn B, Reitemeyer S, Giger U, et alEtablierung einer Blutbank für Hunde an einer Universitäts-Kleintierklinik. Kleintierpraxis 2000;45:331–349.

    • Search Google Scholar
    • Export Citation

  • 27. Reitemeyer S, Kohn B, Brunnberg L, et alTransfusionen von Vollblut und Erythrozytenkonzentrat beim Hund. Kleintierpraxis 2000;45:669–684.

    • Search Google Scholar
    • Export Citation

  • 28. Schneider A. Principles of blood collection and processing. In: Feldman BF, Zinkl JG, Jain NC, eds. Schalm's veterinary hematology. Philadelphia: Lippincott Williams & Wilkins, 2000;827–832.

    • Search Google Scholar
    • Export Citation

  • 29. Wergin MC, Ballmer-Hofer K, Roos M, et alPreliminary study of plasma vascular endothelial growth factor (VEGF) during low- and high-dose radiation therapy of dogs with spontaneous tumors. Vet Radiol Ultrasound 2004;45:247–254.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 30. Quantikine [package insert]. Abington, Oxfordshire, England: R&D systems, 2007.

  • 31. Scheidegger P, Weiglhofer W, Suarez S, et alVascular endothelial growth factor (VEGF) and its receptors in tumor-bearing dogs. Biol Chem 1999;380:1449–1454.

    • Search Google Scholar
    • Export Citation

  • 32. Clifford CA, Hughes D, Beal MW, et alPlasma vascular endothelial growth factor concentrations in healthy dogs and dogs with hemangiosarcoma. J Vet Intern Med 2001;15:131–135.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 33. Dittadi R, Meo S, Fabris F, et alValidation of blood collection procedures for the determination of circulating vascular endothelial growth factor (VEGF) in different blood compartments. Int J Biol Markers 2001;16:87–96.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 34. George ML, Eccles SA, Tutton MG, et alCorrelation of plasma and serum vascular endothelial growth factor levels with platelet count in colorectal cancer: clinical evidence of platelet scavenging? Clin Cancer Res 2000;6:3147–3152.

    • Search Google Scholar
    • Export Citation

  • 35. Verheul HM, Hoekman K, Luykx-de Bakker S, et alPlatelet: transporter of vascular endothelial growth factor. Clin Cancer Res 1997;3:2187–2190.

    • Search Google Scholar
    • Export Citation

  • 36. Kato Y, Asano K, Mogi T, et alClinical significance of circulating vascular endothelial growth factor in dogs with mammary gland tumors. J Vet Med Sci 2007;69:77–80.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 37. Gunsilius E, Petzer A, Stockhammer G, et alThrombocytes are the major source for soluble vascular endothelial growth factor in peripheral blood. Oncology 2000;58:169–174.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 38. Vermeulen PB, Salven P, Benoy I, et alBlood platelets and serum VEGF in cancer patients. Br J Cancer 1999;79:370–373.

  • 39. Edvardsen L, Taaning E, Dreier B, et alExtracellular accumulation of bioactive substances during preparation and storage of various platelet concentrates. Am J Hematol 2001;67:157–162.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 40. Chernoff A, Snyder EL. The cellular and molecular basis of the platelet storage lesion: a symposium summary. Transfusion 1992;32:386–390.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 41. Callaerts AJ, Gielis ML, Sprengers ED, et alThe mechanism of white cell reduction by synthetic fiber cell filters. Transfusion 1993;33:134–138.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 42. Steneker I, Prins HK, Florie M, et alMechanisms of white cell reduction in red cell concentrates by filtration: the effect of the cellular composition of the red cell concentrates. Transfusion 1993;33:42–50.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 43. van der Meer PF, Pietersz RNI, Nelis JT, et alSix filters for the removal of white cells from red cell concentrates, evaluated at 4°C and/or room temperature. Transfusion 1999;39:265–270.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 44. Metcalfe P, Williamson LM, Reutelingsperger CPM, et alActivation during preparation of therapeutic platelets affects deterioration during storage: a comparative flow cytometric study of different production methods. Br J Haematol 1997;98:86–95.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 45. Nielsen HJ, Reimert C, Pedersen AN, et alLeucocyte-derived bioactive substances in fresh frozen plasma. Br J Anaesth 1997;78:548–552.

  • 46. Willis JI, Lown JAG, Simpson MC, et alWhite cells in fresh-frozen plasma: evaluation of a new white cell-reduction filter. Transfusion 1998;38:645–649.

    • Crossref
    • Search Google Scholar
    • Export Citation

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