PMID- 34951486
OWN - NLM
STAT- MEDLINE
DCOM- 20220412
LR  - 20220729
IS  - 1537-2995 (Electronic)
IS  - 0041-1132 (Print)
IS  - 0041-1132 (Linking)
VI  - 62
IP  - 2
DP  - 2022 Feb
TI  - Characterization and first-in-human clinical dose-escalation safety evaluation of 
      a next-gen human freeze-dried plasma.
PG  - 406-417
LID - 10.1111/trf.16756 [doi]
AB  - BACKGROUND: Early plasma transfusion is life-saving for bleeding trauma patients. 
      Freeze-dried plasma (FDP) provides unique formulation advantages for infusion in 
      the prehospital setting. We describe characterization and clinical safety data of 
      the first, next-generation FDP stored in plastic bags with rapid reconstitution. 
      STUDY DESIGN AND METHODS: Coagulation and chemistry parameters on 155 pairs of 
      fresh frozen plasma (FFP) and their derivative FDP units were compared. Next, a 
      first-in-human, dose-escalation safety evaluation of FDP, involving 24 healthy 
      volunteers who donated either whole blood or apheresis plasma to create 
      autologous FDP, was performed in three dose cohorts (270, 540, and 810 ml) and 
      adverse events (AEs) were monitored. Cohort 3 was randomized, double-blind with a 
      cross-over arm that compared FDP versus FFP using descriptive analysis for AEs, 
      coagulation, hematology, and chemistry parameters. RESULTS: FDP coagulation 
      factors, clotting times, and product quality (pH, total protein, and osmolality) 
      post-lyophilization were preserved. FDP infusions, of up to 810 ml per subject, 
      were found to be safe and with no serious AEs (SAEs) related to FDP. The average 
      time to reconstitute FDP was 67 s (range: 43-106). No differences in coagulation 
      parameters or thrombin activation were detected in subjects infused with 810 ml 
      of FDP compared with FFP. CONCLUSION: This first next-generation FDP product 
      preserves the potency and safety of FFP in a novel rugged, compressible, plastic 
      container, for rapid transfusion, allowing rapid access to plasma in 
      resuscitation protocols for therapy in acute traumatic hemorrhage.
CI  - (c) 2021 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of 
      AABB.
FAU - Cancelas, Jose A
AU  - Cancelas JA
AUID- ORCID: 0000-0002-1291-7233
AD  - Hoxworth Blood Center, University of Cincinnati College of Medicine, Cincinnati, 
      Ohio, USA.
FAU - Nestheide, Shawnagay
AU  - Nestheide S
AD  - Hoxworth Blood Center, University of Cincinnati College of Medicine, Cincinnati, 
      Ohio, USA.
FAU - Rugg, Neeta
AU  - Rugg N
AD  - Hoxworth Blood Center, University of Cincinnati College of Medicine, Cincinnati, 
      Ohio, USA.
FAU - Eckerman, Anna
AU  - Eckerman A
AD  - Vascular Solutions LLC, Minneapolis, Minnesota, USA.
FAU - Macdonald, Victor W
AU  - Macdonald VW
AD  - US Army Medical Materiel Development Activity (USAMMDA), Ft. Detrick, Maryland, 
      USA.
FAU - L Charles, Matthew
AU  - L Charles M
AD  - Vascular Solutions LLC, Minneapolis, Minnesota, USA.
FAU - Markstrom, Luke
AU  - Markstrom L
AD  - Vascular Solutions LLC, Minneapolis, Minnesota, USA.
FAU - Atkinson, Andrew J
AU  - Atkinson AJ
AD  - US Army Medical Materiel Development Activity (USAMMDA), Ft. Detrick, Maryland, 
      USA.
FAU - King, Melissa R
AU  - King MR
AD  - Westat Inc., Rockville, Maryland, USA.
FAU - Snyder, Michele
AU  - Snyder M
AD  - Westat Inc., Rockville, Maryland, USA.
FAU - Burgess, David
AU  - Burgess D
AD  - Westat Inc., Rockville, Maryland, USA.
FAU - Murto, James
AU  - Murto J
AD  - Vascular Solutions LLC, Minneapolis, Minnesota, USA.
FAU - Valiyaveettil, Manoj K
AU  - Valiyaveettil MK
AD  - US Army Medical Materiel Development Activity (USAMMDA), Ft. Detrick, Maryland, 
      USA.
FAU - C Pehta, Joan
AU  - C Pehta J
AD  - The Alpha Bio Group, New Canaan, Connecticut, USA.
FAU - Penegor, Stephen A
AU  - Penegor SA
AD  - Vascular Solutions LLC, Minneapolis, Minnesota, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20211224
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
SB  - IM
CIN - Transfusion. 2022 Feb;62(2):257-260. PMID: 35044700
MH  - *Blood Component Transfusion
MH  - Freeze Drying/methods
MH  - Hemorrhage/therapy
MH  - Humans
MH  - *Plasma
MH  - Resuscitation/methods
PMC - PMC9306459
OTO - NOTNLM
OT  - coagulation
OT  - freeze-dried plasma
OT  - hemorrhage
OT  - next generation
OT  - safety
COIS- The authors declare that AE, MLC, LM, JM, SP are employees of Vascular Solutions 
      LLC, a wholly-owned subsidiary of Teleflex Incorporated. JCP and VWM are paid 
      consultants for Teleflex/Vascular Solutions LLC. AJA and MKV are employees of the 
      US Federal Government. The opinions presented in this publication do not 
      represent those of the US Army or the Department of Defense. No other relevant 
      conflicts of interest.
EDAT- 2021/12/25 06:00
MHDA- 2022/04/13 06:00
PMCR- 2022/07/22
CRDT- 2021/12/24 09:04
PHST- 2021/10/27 00:00 [revised]
PHST- 2021/08/16 00:00 [received]
PHST- 2021/11/16 00:00 [accepted]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2022/04/13 06:00 [medline]
PHST- 2021/12/24 09:04 [entrez]
PHST- 2022/07/22 00:00 [pmc-release]
AID - TRF16756 [pii]
AID - 10.1111/trf.16756 [doi]
PST - ppublish
SO  - Transfusion. 2022 Feb;62(2):406-417. doi: 10.1111/trf.16756. Epub 2021 Dec 24.