title: Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study.
abstract: BACKGROUND
  The rapid reversal of the effects of vitamin K antagonists is often required in cases of emergency surgery and life-threatening bleeding, or during bleeding associated with high morbidity and mortality such as intracranial haemorrhage. Increasingly, four-factor prothrombin complex concentrates (PCCs) containing high and well-balanced concentrations of vitamin K-dependent coagulation factors are recommended for emergency oral anticoagulation reversal. Both the safety and efficacy of such products are currently in focus, and their administration is now expanding into the critical care setting for the treatment of life-threatening bleeding and coagulopathy resulting either perioperatively or in cases of acute trauma.
  
  
  METHODS
  After 15 yr of clinical use, findings of a pharmacovigilance report (February 1996-March 2012) relating to the four-factor PCC Beriplex P/N (CSL Behring, Marburg, Germany) were analysed and are presented here. Furthermore, a review of the literature with regard to the efficacy and safety of four-factor PCCs was performed.
  
  
  RESULTS
  Since receiving marketing authorization (February 21, 1996), ~647 250 standard applications of Beriplex P/N have taken place. During this time, 21 thromboembolic events judged to be possibly related to Beriplex P/N administration have been reported, while no incidences of viral transmission or heparin-induced thrombocytopenia were documented. The low risk of thromboembolic events reported during the observation period (one in ~31 000) is in line with the incidence observed with other four-factor PCCs.
  
  
  CONCLUSIONS
  In general, four-factor PCCs have proven to be well tolerated and highly effective in the rapid reversal of vitamin K antagonists.
authors: Department of Anesthesiology and Intensive Care, Hannover Medical School, Carl-Neuberg-Str 1, D-30625 Hannover, Germany. hanke.alexander@mh-hannover.de
authors: A A
authors: AA
authors: Hanke
authors: C
authors: C
authors: Joch
authors: K
authors: K
authors: Görlinger
mesh_terms: D000925:Anticoagulants / Q000037:antagonists & inhibitors; D003029:Coagulants / Q000009:adverse effects* / Q000627:therapeutic use; D004338:Drug Combinations; D005164:Factor IX / Q000009:adverse effects* / Q000627:therapeutic use; D005167:Factor VII / Q000009:adverse effects* / Q000627:therapeutic use; D005170:Factor X / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D036103:Nanotechnology / Q000379:methods; D060735:Pharmacovigilance; D011516:Prothrombin / Q000009:adverse effects* / Q000627:therapeutic use; D013923:Thromboembolism / Q000139:chemically induced; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D003029:Coagulants; D004338:Drug Combinations; C525441:factor IX, factor VII, factor X, prothrombin drug combination; D014812:Vitamin K; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X