Annals of Hematology

, Volume 89, Issue 3, pp 309–316 | Cite as

Impact of infusion speed on the safety and effectiveness of prothrombin complex concentrate

A prospective clinical trial of emergency anticoagulation reversal
  • Ingrid Pabinger
  • Andreas Tiede
  • Uwe Kalina
  • Sigurd Knaub
  • Reinhard Germann
  • Helmut Ostermann
  • for the Beriplex® P/N Anticoagulation Reversal Study Group
Original Article

Abstract

Prothrombin complex concentrate (PCC) infusion is preferred for emergency reversal of coumarin therapy. Rapid infusion can potentially save crucial time; however, the possible impact of high infusion speed on PCC safety and effectiveness has not been delineated. In a prospective multinational clinical trial with 43 patients receiving PCC (Beriplex® P/N) for emergency reversal of coumarin therapy, infusion speeds were selected by the investigators. In a two-phase statistical analysis, the influence of baseline patient variables and dose on selected infusion speed was assessed. Then, the effect of infusion speed on reduction in international normalized ratio (INR) and on thrombogenicity marker pharmacokinetics was evaluated. Infusion speed ranged widely from 2.0 to 40.0 mL min−1 with a median of 7.5 mL min−1. Selection of infusion speed was not significantly influenced by gender, age, body mass index, presence of acute bleeding, indication for coumarin therapy, baseline INR, or PCC dose. Infusion speed was higher by a median of 2.2 mL min−1 (95% confidence interval, 1.0–4.3 mL min−1) among patients receiving Beriplex P/N volumes ≥80 mL compared with smaller infusion volumes. Infusion speed did not affect INR attained 30 min following PCC infusion. None of the evaluated thrombogenicity marker pharmacokinetic parameters was affected by infusion speed. Infusions in one patient with questionable hemostatic efficacy and another with a possibly PCC-related thromboembolic event were at moderate and slow speeds, respectively. This study provides the first direct evidence that Beriplex® P/N can be rapidly infused for emergency coumarin therapy reversal without altering safety or effectiveness.

Keywords

Infusion speed Prothrombin complex concentrates Anticoagulation reversal Coumarins Surgery Hemorrhage 

Notes

Acknowledgments

This investigation was supported by CSL Behring GmbH, Marburg, Germany.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ingrid Pabinger
    • 1
    • 6
  • Andreas Tiede
    • 2
  • Uwe Kalina
    • 3
  • Sigurd Knaub
    • 3
  • Reinhard Germann
    • 4
  • Helmut Ostermann
    • 5
  • for the Beriplex® P/N Anticoagulation Reversal Study Group
  1. 1.Department of Internal Medicine, Division of Haematology and HaemostaseologyMedical University ViennaViennaAustria
  2. 2.Department of Haematology, Haemostasis, Oncology and Stem Cell TransplantationHannover Medical SchoolHannoverGermany
  3. 3.Clinical Research & DevelopmentHemophilia/Critical Care, CSL Behring GmbHMarburgGermany
  4. 4.Department of Anesthesiology and Intensive Care MedicineAcademic Teaching Hospital FeldkirchFeldkirchAustria
  5. 5.Department of Haematology and Oncology, Medical Clinic IIIUniversity Hospital Munich—Großhadern, Ludwig Maximilian UniversityMunichGermany
  6. 6.Universitätsklinik für Innere Medizin IKlinische Abteilung für Hämatologie und HämostaseologieWienAustria

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