PB0879 - Inhibition of apoptosis during cold storage of platelet concentrates better maintains both platelet functionality and survival

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

IM

Irene Marini

Post Doc
Institute for Clinical and Experimental Transfusion Medicine (IKET), University Hospital of Tuebingen, Germany
stuttgart, Baden-Wurttemberg, Germany

Co-Author(s)

YT

Yoko Tamamushi

Student
Institute for Clinical and Experimental Transfusion Medicine (IKET), University Hospital of Tuebingen, Germany
stuttgart, Baden-Wurttemberg, Germany
CM

Chiara-Tanita Maettler

Student
Institute for Clinical and Experimental Transfusion Medicine (IKET), University Hospital of Tuebingen, Germany
stuttgart, Baden-Wurttemberg, Germany
LP

Lisann Pelzl

Post Doc
Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany
Tuebingen, Baden-Wurttemberg, Germany
Karina Althaus, MD

Physician, Director of Platelet Immunology Lab.
Center for Clinical Transfusion Medicine, University Hospital of Tübingen
Tübingen, Baden-Wurttemberg, Germany
SN

Stefanie Nowak-Harnau

Physician
Center for Clinical Transfusion Medicine
Tübingen, Baden-Wurttemberg, Germany
Tamam Bakchoul, MD

Medical Director
Center for Clinical Transfusion Medicine, University Hospital of Tübingen
Tübingen, Baden-Wurttemberg, Germany

Background: Apheresis-derived platelet concentrates (APCs) is an essential medical treatment. However, the storage at room temperature enhances the risk of bacterial contamination. Recently, we showed that cold storage of APCs better conserves platelet functions but reduced cell half-life because of apoptosis activation.

Aims: To investigated the impact of apoptosis inhibition on platelet functions and half-life during cold storage.

Methods: APCs were stored for 7 days at 4°C with or without the apoptosis inhibitor G04 (RhoA-GTPase inhibitor). The functionality of cold-stored platelets was assessed by flow cytometer (CD63, CD62 and PAC expression, upon TRAP), aggregometry assay and thrombin generation. The platelet responsiveness to extracellular matrix proteins was determined using the platelet adhesion assay. Platelet survival was investigated using the NOD/SCID mouse model.

Results: The presence of the inhibitor better maintains CD63 and PAC1 expression during cold storage (CD63, p=0.035; PAC1, p=0.005). No differences in the expression of CD62 were observed with or without inhibitor (p=0.728). Furthermore, the capability to generate thrombin was not impaired in the presence of G04 (p=0.956). Interestingly, the aggregation ability was better conserves in platelet incubated with G04 (TRAP, p=0.019). Next, comparable adhesion ability was detected with or without inhibitor (p=0.447). More importantly, the inhibition of apoptosis induced a significant higher percentage of circulating cold-stored platelets in vivo compared to untreated cells (5h post injection, p=0.046).

Conclusion(s): Our results show that the inhibition of the apoptotic pathway significantly reduces the clearance of cold-stored platelets without affecting cell functionality. Therefore, the use of apoptosis inhibitors may be a promising strategy to prolong the storage time and reduce the risk of bacterial infection post-transfusion.