title: Recombinant human macrophage colony-stimulating factor-induced thrombocytopenia in dogs.
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.
authors.affiliation: Puget Sound Blood Center, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109-1024, USA.
authors.forename: Kraig
authors.initials: K
authors.lastname: Abrams
authors.forename: Murad Y
authors.initials: MY
authors.lastname: Yunusov
authors.forename: Sherrill
authors.initials: S
authors.lastname: Slichter
authors.forename: Peter
authors.initials: P
authors.lastname: Moore
authors.forename: Wil B
authors.initials: WB
authors.lastname: Nelp
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Burstein
authors.forename: Sean
authors.initials: S
authors.lastname: McDonough
authors.forename: Lawrence
authors.initials: L
authors.lastname: Durack
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: M John
authors.initials: MJ
authors.lastname: Gass
authors.forename: George
authors.initials: G
authors.lastname: Georges
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002470:Cell Survival; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver; D016173:Macrophage Colony-Stimulating Factor / Q000009:adverse effects*; D010976:Platelet Count; D013154:Spleen; D013921:Thrombocytopenia / Q000139:chemically induced*
chemical_list: D016173:Macrophage Colony-Stimulating Factor