Recombinant human macrophage colony-stimulating factor-induced thrombocytopenia in dogs

Kraig Abrams, Murad Y. Yunusov, Sherrill Slichter, Peter F Moore, Wil B. Nelp, Samuel A. Burstein, Sean McDonough, Lawrence Durack, Barry Storer, Rainer Storb, M. John Gass, George Georges, Richard A. Nash

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11 Scopus citations

Abstract

To characterize recombinant human macrophage-colony stimulating factor (rhM-CSF)-associated thrombocytopenia (TCP), in vivo studies were performed in dogs, including the biodistributions and recoveries of radiolabelled autologous and allogeneic platelets. rhM-CSF induced a reversible, dose-dependent decrease in platelet counts. The number of megakaryocytes in spleen and marrow of rhM-CSF-treated dogs was increased two to threefold. Recoveries of allogeneic platelets transfused from rhM-CSF-treated donors into tolerized recipients (n = 3) were not significantly different from allogeneic baseline studies (93 ± 10% of baseline values at 24 h and 90 ± 1% at 40 h), whereas autologous platelets infused back into rhM-CSF-treated donors had decreased recoveries (45 ± 2% of baseline values at 24 h. P = 0.03 and 20 ± 4% at 40 h. P = 0.001). Platelet biodistribution studies showed increased accumulation of radiolabelled platelets over the spleens and livers of rhM-CSF-treated dogs. Histochemistry showed increased levels of platelet-specific antigen (CD41: glycoprotein IIb) associated with Kupffer cells. The sensitivity of platelets from rhM-CSF-treated dogs to activation from thrombin, as measured by expression of P-selectin (CD62P), was not significantly different when compared with baseline studies (P = 0.18; n = 4). These results support the concept that rhM-CSF induces an activation of the monocyte-macrophage system (MMS), which causes a reversible TCP in a dog model.

Original languageEnglish (US)
Pages (from-to)614-622
Number of pages9
JournalBritish Journal of Haematology
Volume121
Issue number4
DOIs
StatePublished - May 2003

Keywords

  • Dog
  • M-CSF
  • Monocyte-macrophage system
  • Platelets
  • Thrombocytopenia

ASJC Scopus subject areas

  • Hematology

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    Abrams, K., Yunusov, M. Y., Slichter, S., Moore, P. F., Nelp, W. B., Burstein, S. A., McDonough, S., Durack, L., Storer, B., Storb, R., Gass, M. J., Georges, G., & Nash, R. A. (2003). Recombinant human macrophage colony-stimulating factor-induced thrombocytopenia in dogs. British Journal of Haematology, 121(4), 614-622. https://doi.org/10.1046/j.1365-2141.2003.04313.x