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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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
Issue number4
StatePublished - May 2003


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

ASJC Scopus subject areas

  • Hematology


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