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Platelets: Frozen and Freeze-Dried Current Products in Development and Regulatory Licensing Challenges

  • Heather Pidcoke
  • Kathleen Kelly
  • G. Michael Fitzpatrick
  • Larry J. DumontEmail author
Chapter

Abstract

Cryopreserved and lyophilized platelets have a long, but limited, history of human use that dates back to the 1950s yet involves a small number of total study subjects (Fig. 9.1). Despite decades of research characterizing the quality and nature of these products, questions remain regarding the relationship between in vitro performance and in vivo function to control bleeding. That said, results to date indicate promising in vivo hemostatic potential in several animal models. Although the data is retrospective and cannot definitively establish causality, human use of cryopreserved platelets in military settings also appears to be associated with benefit. The regulatory pathway for these products, particularly in the case of cryopreserved platelets, has been decades long, and more trials are needed to provide high-quality data to regulatory bodies. These products could be life-saving in settings where other good alternatives are limited or unavailable.

Keywords

History of platelets Cryopreserved platelets Frozen platelets DMSO Lyophilized platelets Freeze-dried platelets Trehalose Paraformaldehyde US military FDA 

Abbreviations

ACD

Anticoagulant Citrate Dextrose Solution

ADF

Australian Defense Force

ARC

Australian Red Cross

BARDA

Biomedical Advanced Research and Development Authority

BEST

Biomedical Excellence for Safer Transfusion

CABG

Coronary artery bypass grafting

CBER

Center for Biologics Evaluation and Research

CD41a

Cluster of differentiation 41a (GPIIb/IIIa)

CD42b

Cluster of differentiation 42b (GPIb)

cGMP

Current Good Manufacturing Practice

CLIP

Cryopreserved Platelets Versus Liquid Platelets Trial

CPP

Cryopreserved platelet product

DARPA

Defense Advanced Research Projects Agency

DMSO

Dimethyl sulfoxide

DoD

Department of Defense

FDA

Food and Drug Administration

FFP

Fresh frozen plasma

GPIb

Glycoprotein Ib

GPIIb/IIIa

Glycoprotein IIb/IIIa

ICH

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use

LDH

Lactate dehydrogenase

LSP

Liquid-stored platelets

LyPt

Lyophilized platelets

LyPt-P

Lyophilized platelets stabilized with paraformaldehyde

LyPt-T

Lyophilized platelets stabilized with trehalose

MTFs

Medical treatment facilities

NATO

North Atlantic Treaty Organization

NHP

Non-human primate

NIH

National Institutes of Health

NLAF

Netherlands Armed Forces

NZWR

New Zealand white rabbits

PAS

Platelet additive solution

PVC

Polyvinyl chloride

RT

Room temperature, 20–24 °C

US

United States

WB

Whole blood

Notes

Disclosure

Funding for some research studies reported here was from the US Army Medical Research and Materiel Command. The views, opinions, and/or findings contained in this report are those of the authors and should not be construed as an official Department of Defense position, policy, or decision unless so designated by other documentation.

Funding for some research studies reported here was provided in whole or in part with federal funds from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services, under Contract No. HHSO100201300021C.

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Heather Pidcoke
    • 1
  • Kathleen Kelly
    • 2
  • G. Michael Fitzpatrick
    • 3
  • Larry J. Dumont
    • 2
    • 4
    • 5
    Email author
  1. 1.Department of Clinical AffairsCellphire, Inc.RockvilleUSA
  2. 2.Vitalant Research Institute (VRI)DenverUSA
  3. 3.Clinical Research and DevelopmentCellphire, Inc.RockvilleUSA
  4. 4.The Geisel School of Medicine at DartmouthLebanonUSA
  5. 5.University of Colorado School of MedicineDenverUSA

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