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

A prospective clinical trial of emergency anticoagulation reversal

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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.

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Acknowledgments

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

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Haematology and Haemostaseology, Medical University Vienna, Vienna, Austria

    Ingrid Pabinger

  2. Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    Andreas Tiede

  3. Clinical Research & Development, Hemophilia/Critical Care, CSL Behring GmbH, Marburg, Germany

    Uwe Kalina & Sigurd Knaub

  4. Department of Anesthesiology and Intensive Care Medicine, Academic Teaching Hospital Feldkirch, Feldkirch, Austria

    Reinhard Germann

  5. Department of Haematology and Oncology, Medical Clinic III, University Hospital Munich—Großhadern, Ludwig Maximilian University, Munich, Germany

    Helmut Ostermann

  6. Universitätsklinik für Innere Medizin I, Klinische Abteilung für Hämatologie und Hämostaseologie, Währinger Gürtel 18-20, 1090, Wien, Austria

    Ingrid Pabinger

Authors
  1. Ingrid Pabinger
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  2. Andreas Tiede
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  3. Uwe Kalina
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  4. Sigurd Knaub
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  5. Reinhard Germann
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  6. Helmut Ostermann
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Consortia

for the Beriplex® P/N Anticoagulation Reversal Study Group

Corresponding author

Correspondence to Ingrid Pabinger.

Appendix

Appendix

The members of the Beriplex® P/N Anticoagulation Reversal Study Group are:

Jürgen Barth, Specialty Clinics, Bergmannstrost Medical Clinic, Halle/Salle, Germany

Brigitte Brand-Staufer, Clinical Department of Hematology, University Hospital Zürich, Zürich, Switzerland

Benjamin Brenner, Thrombosis and Hemostasis Unit, Rambam Medical Center, Haifa, Israel

Reinhard Germann, Department of Anesthesiology and Intensive Care, County Hospital Feldkirch, Feldkirch, Austria

Rasa Griniute, Kaunas Medical University Clinic, Kaunas, Lithuania

Uwe Kalina, Clinical Research & Development, Hemophilia/Critical Care, CSL Behring GmbH, Marburg, Germany

Ralph Kätzel, Institute for Transfusion Medicine and Clinical Hemostaseology, Municipal Clinic “St. Georg” Leipzig, Leipzig, Germany

Gintautas Kekstas, Centre of Anesthesiology, Intensive Therapy and Pain Management, Santariskiu Clinics, Vilnius University Hospital, Vilnius, Lithuania

Sigurd Knaub, Clinical Research & Development, Hemophilia/Critical Care, CSL Behring GmbH, Marburg, Germany

Saskia Middeldorp, Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

Attila Nagy, Department of Surgery, Csolnoky Ferenc County Hospital, Veszprém, Hungary

Attila Oláh, Department of Surgery, Petz Aladár Teaching Hospital, Györ, Hungary

Helmut Ostermann, Department of Hematology and Oncology, Medical Clinic III, University Hospital Munich—Großhadern, Ludwig Maximilian University, Munich, Germany

Ingrid Pabinger, Department of Internal Medicine, Division of Hematology and Hemostaseology, Medical University Vienna, Vienna, Austria

Tibor Retteghy, Institute of Traumatology and Emergency, Budapest, Hungary

Jacek Szmidt, Department of General, Vascular and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland

Andreas Tiede, Department of Hematology, Hemostaseology and Oncology, Center for Internal Medicine, Medical College Hannover, Hannover, Germany

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Pabinger, I., Tiede, A., Kalina, U. et al. Impact of infusion speed on the safety and effectiveness of prothrombin complex concentrate. Ann Hematol 89, 309–316 (2010). https://doi.org/10.1007/s00277-009-0830-7

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  • DOI: https://doi.org/10.1007/s00277-009-0830-7

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