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Randomized Controlled Trial
. 2018 Dec;58(12):2969-2977.
doi: 10.1111/trf.14972. Epub 2018 Nov 18.

Safety evaluation of a lyophilized platelet-derived hemostatic product

Jeffrey Barroso  1 , Barbara Osborne  1 , Gayle Teramura  1 , Esther Pellham  1 , Michael Fitzpatrick  2 , Ruth Biehl  2 , Anna Yu  2 , Joan Pehta  2 , Sherrill J Slichter  1   3
Affiliations
Randomized Controlled Trial

Safety evaluation of a lyophilized platelet-derived hemostatic product

Jeffrey Barroso et al. Transfusion. 2018 Dec.

Abstract

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.

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Conflict of interest statement

Conflict of Interest: Jeffrey Barroso, Barbara Osborne, Gayle Teramua, Esther Pellham, and Sherrill J. Slichter have disclosed no conflicts of interest.

Figures

FIGURE 1:
FIGURE 1:. EKG Treatment Emergent Adverse Events - Subject 83.
The subject had two normal EKGs prior to infusion. At one-hour post her second Thrombosomes infusion in Cohort 5, she demonstrated T-wave inversions in Leads V2 and V3 which resolved by Day 21.
FIGURE 2:
FIGURE 2:. Autoplatelet Antibody Test Results Through Day 60 - Subject 90.
The subject’s platelets exhibited mean fluorescent intensity (MFI) results that were positive (MFI > the mean of the Neg. control plus 3 SD on days 7, 14, and 21 and were negative on screen, baseline, and days 42 and 60 post infusion. Positive control MFI values were 140 to 300 while the subject’s highest MFI was 7 and the mean negative control plus 3SD selected as the cutoff to indicate a positive result ranged from was 4.0 to 5.6
See this image and copyright information in PMC

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