Abstract Number: PB0483
Meeting: ISTH 2020 Congress
Theme: Diagnostics and OMICs » Blood Components and Management
Background: Transfusion of apheresis platelet concentrates (APCs) is an established therapy to treat bleeding. However, bacterial infection caused by storage at room temperature (RT) still remains a major problem. Recently, we reported that cold-stored APCs (C-APCs) are associated with better PLT functionality but faster PLT clearance caused by apoptosis activation.
Aims: To investigate the protective effect of apoptotic inhibitor during cold storage of APCs and its impact on PLT functionality.
Methods: APCs were stored at RT and 4°C with or without a caspase-3 inhibitor. PLT apoptosis was assessed measuring the mitochondrial membrane potential (MMP), phosphatidylserine exposure by flow cytometry and protein expression via immune blot. The PLT aggregation ability was analyzed performing an aggregation Assay.
Results: In C-APCs a higher phosphatidylserine expression was detected compared to RT
(RT-APCs) (% apoptotic events mean±SEM: 13±1% vs. 5±1%, C- vs. RT-APCs, p=0.018). Interestingly, a reduction of MMP after cold storage compared to RT was observed (mean fluorescence intensity TMRE Mean±SEM: 6.13±1.89 vs. 18.53±3.64, C- vs. RT-APCs, p=0.038). Accordingly, the procaspase-3 protein level in immune blot was found to be decreased upon cold storage. These data, indicate the activation of the intrinsic apoptotic pathway during cold storage of PLTs. In the presence of a caspase-3 inhibitor a significant rescue of the cold-stored PLTs viability was observed (% alive cells mean±SEM: 74±3% vs. 22±3%, caspase-3 inhibitor vs. ionomycin, p=0.005) suggesting that the caspase inhibitor can prevent the cold-induced apoptosis. Importantly, the caspase-3 inhibitor doesn´t affect the PLT aggregation ability that is comparable to PLTs stored without the inhibitor (% maximal aggregation in response to TRAP mean±SEM: 76.24±5.63 vs. 66.91±16.06 without vs. with caspase-3 inhibitor, p=0.638).
Conclusions: These results demonstrate that cold-induced apoptosis can be prevented by a caspase-3 inhibitor without affecting PLT aggregation capability. Consequently, cold storage may become an efficient strategy for APC storage in combination with apoptotic inhibitors.
To cite this abstract in AMA style:
Marini I, Tamamushi Y, Pelzl L, Althaus K, Nowak-Harnau S, Bakchoul T. Apoptosis Inhibition during Cold Storage of Apheresis Platelet Concentrates Improves Cell Vitality without Affecting the Functionality [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/apoptosis-inhibition-during-cold-storage-of-apheresis-platelet-concentrates-improves-cell-vitality-without-affecting-the-functionality/. Accessed March 21, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/apoptosis-inhibition-during-cold-storage-of-apheresis-platelet-concentrates-improves-cell-vitality-without-affecting-the-functionality/