title: A case series of recombinant platelet factor 4 for heparin reversal after cardiopulmonary bypass.
abstract: BACKGROUND
  Platelet factor 4 (PF4) is released by activated platelets and has a strong affinity for heparin. Recombinant PF4 (rPF4) has been previously considered as an alternative to protamine for heparin reversal. However, it has been demonstrated that antibodies directed against the PF4/heparin moiety are important in the pathophysiologic development of heparin-induced thrombocytopenia, a prothrombotic complication for which cardiac bypass patients are at increased risk.
  
  
  METHODS
  We retrospectively analyzed a case series from an open-label, comparative phase I-II study of rPF4 and protamine after cardiac surgery to determine the heparin-reversal activity of different doses of IV rPF4. Sixteen patients received rPF4, and 5 received protamine. Activated clotting time (ACT) was used to monitor heparin reversal, with reversal defined as ACT <150 seconds. Platelets, white blood cells, C3a, C5a, fibrinopeptide A, von Willebrand factor antigen, and prothrombin fragment 1.2 were monitored postoperatively as indicators of coagulation and inflammation.
  
  
  RESULTS
  Heparin reversal was successful by 10 minutes after administration of rPF4 as measured by ACT in all 16 patients. Specifically, a dose of 5 mg/kg rPF4 resulted in ACT <150 seconds after 5 minutes in 10 of 10 patients. For both treatment groups, there were no bleeding or thrombotic complications, no clinical thrombocytopenia after day 5, and no deaths within the 30-day study period.
  
  
  CONCLUSIONS
  Our case series demonstrates that heparin anticoagulation was effectively reversed by the administration of rPF4 without serious complications. Additional studies are needed to further validate the safety and efficacy of exogenous rPF4 administration.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine , Emory University Hospital, 1364 Clifton Rd., Atlanta, GA 30322, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Demma
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
mesh_terms: D000328:Adult; D000368:Aged; D001779:Blood Coagulation Factors / Q000032:analysis; D001780:Blood Coagulation Tests; D002315:Cardiopulmonary Bypass / Q000401:mortality; D006494:Heparin Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D008875:Middle Aged; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000188:drug therapy / Q000401:mortality; D019106:Postoperative Hemorrhage / Q000188:drug therapy / Q000401:mortality; D011479:Protamines / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology; D013927:Thrombosis / Q000188:drug therapy / Q000401:mortality
chemical_list: D001779:Blood Coagulation Factors; D006494:Heparin Antagonists; D011479:Protamines; D011994:Recombinant Proteins; D010978:Platelet Factor 4