PMID- 30450601
OWN - NLM
STAT- MEDLINE
DCOM- 20190409
LR  - 20200309
IS  - 1537-2995 (Electronic)
IS  - 0041-1132 (Print)
IS  - 0041-1132 (Linking)
VI  - 58
IP  - 12
DP  - 2018 Dec
TI  - Safety evaluation of a lyophilized platelet-derived hemostatic product.
PG  - 2969-2977
LID - 10.1111/trf.14972 [doi]
AB  - BACKGROUND: Hemorrhage causes significant morbidity and mortality in people aged 
      <65 years. A lyophilized platelet-derived hemostatic agent (Thrombosomes) 
      demonstrated hemostatic efficacy in animal models. We report the results of the 
      first safety trial of autologous Thrombosomes given to normal subjects. STUDY 
      DESIGN AND METHODS: Ten subjects received autologous Thrombosomes prepared from 
      their apheresis platelets, and five control subjects received a buffer solution. 
      There were five cohorts, with three subjects per cohort (two in the Thrombosomes 
      group and one in the control group). Doses escalated from 1/1,000 to 1/10 of a 
      proposed efficacious dose. Cohorts 4 and 5 received the highest dose, but in 
      Cohort 5, one-half the dose was infused 2 hours apart. Cohorts 1 through 3 were 
      monitored for 42 days, Cohorts 4 and 5 were monitored for 60 days using 
      hematology, coagulation, and chemistry assays and antibody testing. RESULTS: 
      There were no serious adverse events (AEs) and no subject withdrawals. There were 
      eight treatment-related AEs (TRAEs) in 5 of 15 subjects (33%) (four in the 
      Thrombosomes group and one in the control group). Of four subjects receiving the 
      highest doses, three had TRAEs. One had elevated D-dimer, prothrombin fragment 1 
      + 2, and white blood cell count (subject had concurrent upper respiratory tract 
      infection); one had T-wave inversions in precordial leads V2 and V3 without 
      elevated troponin or symptoms; and one had a platelet autoantibody without change 
      in platelet count. All subjects' TRAEs resolved by Day 21. CONCLUSION: There were 
      no serious AEs in this small study. Thrombosomes were considered safe at the 
      doses assessed. Future, larger trials will be needed to further assess safety and 
      efficacy.
CI  - (c) 2018 AABB.
FAU - Barroso, Jeffrey
AU  - Barroso J
AD  - Research Institute, Bloodworks Northwest, Seattle, Washington.
FAU - Osborne, Barbara
AU  - Osborne B
AD  - Research Institute, Bloodworks Northwest, Seattle, Washington.
FAU - Teramura, Gayle
AU  - Teramura G
AD  - Research Institute, Bloodworks Northwest, Seattle, Washington.
FAU - Pellham, Esther
AU  - Pellham E
AD  - Research Institute, Bloodworks Northwest, Seattle, Washington.
FAU - Fitzpatrick, Michael
AU  - Fitzpatrick M
AD  - Cellphire, Inc., Rockville, Maryland.
FAU - Biehl, Ruth
AU  - Biehl R
AD  - Cellphire, Inc., Rockville, Maryland.
FAU - Yu, Anna
AU  - Yu A
AD  - Cellphire, Inc., Rockville, Maryland.
FAU - Pehta, Joan
AU  - Pehta J
AD  - Cellphire, Inc., Rockville, Maryland.
FAU - Slichter, Sherrill J
AU  - Slichter SJ
AD  - Research Institute, Bloodworks Northwest, Seattle, Washington.
AD  - University of Washington School of Medicine, Seattle, Washington.
LA  - eng
GR  - UL1 TR002319/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20181118
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
RN  - 0 (Fibrin Fibrinogen Degradation Products)
RN  - 0 (Hemostatics)
RN  - 0 (Peptide Fragments)
RN  - 0 (fibrin fragment D)
RN  - 0 (prothrombin fragment 1.2)
RN  - 9001-26-7 (Prothrombin)
SB  - IM
MH  - Adult
MH  - Blood Platelets/*chemistry
MH  - *Drug Monitoring
MH  - Female
MH  - Fibrin Fibrinogen Degradation Products/metabolism
MH  - Freeze Drying
MH  - Hemostatics/*administration & dosage/adverse effects/*chemistry
MH  - Humans
MH  - Leukocyte Count
MH  - Male
MH  - Peptide Fragments/blood
MH  - Prothrombin
PMC - PMC6301028
MID - NIHMS993152
COIS- Conflict of Interest: Jeffrey Barroso, Barbara Osborne, Gayle Teramua, Esther 
      Pellham, and Sherrill J. Slichter have disclosed no conflicts of interest.
EDAT- 2018/11/20 06:00
MHDA- 2019/04/10 06:00
PMCR- 2019/12/01
CRDT- 2018/11/20 06:00
PHST- 2018/04/17 00:00 [received]
PHST- 2018/08/16 00:00 [revised]
PHST- 2018/08/16 00:00 [accepted]
PHST- 2018/11/20 06:00 [pubmed]
PHST- 2019/04/10 06:00 [medline]
PHST- 2018/11/20 06:00 [entrez]
PHST- 2019/12/01 00:00 [pmc-release]
AID - 10.1111/trf.14972 [doi]
PST - ppublish
SO  - Transfusion. 2018 Dec;58(12):2969-2977. doi: 10.1111/trf.14972. Epub 2018 Nov 18.