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Use of Plasma in the Management of Central Nervous System Bleeding: Evidence-Based Consensus Recommendations

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Abstract

Introduction

Central nervous system (CNS) hemorrhage is a potentially life-threatening condition, especially in patients with acquired coagulopathy. In this setting, treatment of CNS bleeding includes hemostatic therapy to replenish coagulation factors. There is currently a debate over the hemostatic efficacy of plasma in many clinical settings, alongside increasing concern about transfusion-associated adverse events. Despite these concerns, plasma is widely used. Moreover, plasma transfusion practice is variable and there is currently no uniform approach to treatment of traumatic, surgical or spontaneous CNS hemorrhage. This study addresses the need for guidance on the indications and potential risks of plasma transfusion in these settings. An Expert Consensus Panel was convened to develop recommendations guiding the use of plasma to treat bleeding and/or coagulopathy associated with CNS hemorrhage. The panel did not advise on the best treatment available but rather proposed recommendations to be used in the formulation of local procedures to support emergency physicians in their decision-making process.

Methods

Evidence was systematically gathered from the literature and rated using methods established by the Scottish Intercollegiate Guidelines Network. The evidence was used to develop graded consensus recommendations, which are presented along with the evidence-based rationale for each in this report.

Results

Sixty-five articles were identified covering both vitamin K antagonist-anticoagulation reversal and treatment of bleeding/coagulopathy in non-anticoagulated patients. Recommendations were then developed in four clinical scenarios within each area, and agreed on unanimously by all members of the panel.

Conclusion

The Panel considered plasma to be reasonable therapy for CNS hemorrhage requiring urgent correction of coagulopathy, although physicians should be prepared for potential cardiopulmonary complications, and evidence suggests that alternative therapies have superior risk–benefit profiles. Plasma could not be recommended in the absence of hemorrhage or coagulopathy. Consideration of the absolute risks and benefits of plasma therapy before transfusion is imperative.

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Acknowledgments

We wish to acknowledge the valuable contributions of Michael Diringer MD and Phillip Bahramipour MD in developing these consensus recommendations, John Peter Gruen MD for his critical review of the manuscript, and Neil Blumberg MD, Maureane Hoffman MD, Lewis Kaplan MD, Majed Refaai MD and Johnathan Waters MD for their critical review on behalf of the Society for Advancement of Blood Management. The co-chairs (Ira Shulman and Aryeh Shander) were responsible for selecting the Consensus Panel and developing and directing the literature review process. Medical writing support was provided by Timothy J. Tavender, PhD and Sandrine M. Dupré, PhD, Meridian HealthComms, Plumley, Cheshire, UK. The logistical framework for the Panel meeting was provided by Interactive Forums Inc.

CSL Behring provided funding support for the following: honoraria payments and expenses reimbursement for Consensus Panel members for preparation and participation in the Panel; honoraria payment and administrative fee to The Society for the Advancement of Blood Management for independent review of the evidence-based recommendations; administrative/logistical support for the Consensus Panel meeting from Interactive Forums Inc.; and medical writing support for literature searches and manuscript preparation from Meridian HealthComms. All work, including the literature review, Panel meeting and manuscript development, was performed independently of the sponsor; the sponsor had no authorship or editorial control over the content of the meeting or any subsequent publication.

Conflict of interest

A. Shander received honoraria payment and expenses reimbursement from CSL Behring for attending the Consensus Panel meeting. E.A. Michelson received honoraria payment and expenses reimbursement from CSL Behring for attending the Consensus Panel meeting. B. Sarani received honoraria payment and expenses reimbursement from CSL Behring for attending the Consensus Panel meeting. I.A. Shulman received honoraria payment and expenses reimbursement from CSL Behring for attending the Consensus Panel meeting. The authors received no subsequent payment for manuscript development. M.L. Flaherty is the Principal Investigator of a phase II treatment trial (funded by the National Institute of Neurological Disorders and Stroke) testing recombinant activated factor VII (supplied by Novo Nordisk) for intracerebral haemorrhage and received honoraria payment and expenses reimbursement from CSL Behring for attending the Consensus Panel meeting.

Compliance with ethics guidelines

The study is based on previously conducted studies, and does not involve any new studies of human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Englewood Hospital and Medical Center, Englewood, NJ, USA

    Aryeh Shander

  2. Departments of Anesthesiology, Medicine and Surgery, Mount Sinai School of Medicine, New York, NY, USA

    Aryeh Shander

  3. Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Edward A. Michelson

  4. University Hospitals Case Medical Center, Cleveland, OH, USA

    Edward A. Michelson

  5. Department of Surgery, Trauma and Acute Care Surgery, George Washington University, Washington, DC, USA

    Babak Sarani

  6. Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH, USA

    Matthew L. Flaherty

  7. Transfusion Medicine Services Group, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Ira A. Shulman

  8. Department of Pathology, University of Southern California Medical Center, Los Angeles, CA, USA

    Ira A. Shulman

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  1. Aryeh Shander
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  2. Edward A. Michelson
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  3. Babak Sarani
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  4. Matthew L. Flaherty
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  5. Ira A. Shulman
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Correspondence to Ira A. Shulman.

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Shander, A., Michelson, E.A., Sarani, B. et al. Use of Plasma in the Management of Central Nervous System Bleeding: Evidence-Based Consensus Recommendations. Adv Ther 31, 66–90 (2014). https://doi.org/10.1007/s12325-013-0083-7

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