title: Severe romiplostim-induced rebound thrombocytopenia after splenectomy for refractory ITP.
abstract: OBJECTIVE
  To report a case of severe rebound thrombocytopenia after temporary discontinuation of romiplostim during splenectomy in the context of refractory immune (idiopathic) thrombocytopenic purpura (ITP).
  
  
  METHODS
  A 65-year-old man with a history of severe refractory ITP failing multiple treatments was considered for romiplostim therapy. He was initiated on 1 µg/kg and titrated upward to 4 µg/kg to elevate and stabilize his platelet levels prior to splenectomy. On day 74 of his clinical course, his platelets increased to 434 × 10(9)/L, and his scheduled dose of romiplostim was withheld on day 75 for fear of romiplostim-induced postsplenectomy rebound thrombocytosis. On day 78, his platelets dropped precipitously to 9 × 10(9)/L, and he experienced multiple episodes of epistaxis. He was reinitiated at 5 µg/kg and soon recovered. He later missed a scheduled dose of romiplostim, and his platelets fell to 23 × 10(9)/L. After resuming romiplostim at 8 µg/kg, his platelets continued to recover.
  
  
  CONCLUSIONS
  Romiplostim, a thrombopoietin mimetic is directly regulated by megakaryocytes and existing circulating platelets via a negative feedback mechanism. This explains the theoretical risk of rapid clearance of romiplostim caused by an increased platelet pool. Clinically, alternative causes of his severe postoperative thrombocytopenia were considered and deemed unlikely. The rebound effect was observed after romiplostim was withdrawn on 2 occasions, and platelet counts improved after restarting romiplostim. The Naranjo Adverse Drug Reaction Probability Score of 7 suggests a probable adverse drug reaction.
  
  
  CONCLUSIONS
  Physicians using romiplostim as a bridge to splenectomy should be cautious about withholding a scheduled dose around the time of surgery.
authors.affiliation: Case Western Reserve School of Medicine, Cleveland Heights, OH, USA mjc206@case.du.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Choe
authors.affiliation: Case Western Reserve School of Medicine, Cleveland Heights, OH, USA Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
authors.forename: Clifford D
authors.initials: CD
authors.lastname: Packer
mesh_terms: D006801:Humans; D008297:Male; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000139:chemically induced* / Q000601:surgery; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins / Q000009:adverse effects*; D013156:Splenectomy; D013921:Thrombocytopenia / Q000139:chemically induced*; D013926:Thrombopoietin / Q000009:adverse effects*
chemical_list: D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim
keywords: TPO; adverse; drug; eltrombopag; events; idiopathic thromobocytic purpura; megakaryocyte; mimetic; platelets; reaction; rebound; refractory; romiplostim; splenectomy; thrombocytosis