title: Diminished response to recombinant factor VIIa in a patient with idiopathic thrombocytopenic purpura.
abstract: OBJECTIVE
  To describe the hypotheses that may explain a diminished hemostatic response in a patient receiving multiple doses of recombinant coagulation factor VIIa (rFVIIa) for off-label treatment of bleeding events.
  
  
  METHODS
  A 70-year-old female with a significant history of idiopathic thrombocytopenic purpura (ITP) was admitted for coronary artery bypass grafting surgery. The patient developed thrombocytopenia and persistent hemorrhage postoperatively that was refractory to conventional therapy for ITP. She experienced an initial hemostatic response to rFVIIa after receiving 3 doses. During her second trial of rFVIIa a few days later, the duration of hemostatic effect was approximately half that of the first. The patient then received rFVIIa almost daily over the following 9 days to which she remained unresponsive, ultimately resulting in death. All doses in this patient were 9.6 mg (101 microg/kg), except the last, which was 4.8 mg (50.5 microg/kg).
  
  
  CONCLUSIONS
  Several hypotheses may explain this patient's resistance to rFVIIa therapy. Two involve depletion of platelets or coagulation factors essential for rFVIIa efficacy. Another involves development of an antibody to rFVIIa. The last involves acidemia, which may interfere with the pharmacologic effect of rFVIIa.
  
  
  CONCLUSIONS
  The combination of persistent thrombocytopenia and exhaustion of coagulation factors is the likely cause leading to resistance to rFVIIa therapy in this patient.
authors.affiliation: Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY 14221-1200, USA.
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Baxter
authors.forename: Walter S
authors.initials: WS
authors.lastname: Schroeder
authors.forename: Yijun
authors.initials: Y
authors.lastname: Cheng
authors.forename: Zale P
authors.initials: ZP
authors.lastname: Bernstein
mesh_terms: D000368:Aged; D004351:Drug Resistance / Q000187:drug effects / Q000502:physiology; D005167:Factor VII / Q000627:therapeutic use*; D015942:Factor VIIa; D005260:Female; D006801:Humans; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000097:blood / Q000150:complications / Q000188:drug therapy
chemical_list: D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa