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Abstract

Biotherapies, Cellular Therapies, and Immunotherapies

Oral Abstract - Platelet Storage

OA4-AM24-MN-14 - Impact Of P38 Mitogen Activated Protein Kinase And Minocycline On Platelets Stored At Cold Temperature For 21 Days

Monday, October 21, 2024
9:45 AM - 10:45 AM  
Location: 332
CE: Zero
Disclosure(s):
Andrey Skripchenko, PhD: No financial relationships to disclose
Background/Case Studies: Cold temperature storage is a promising methodology for preservation of hemostatic platelets (PLTs). Extending PLT cold storage would be advantageous for remote environment applications.  It has been shown that VX-702, an inhibitor of p38 MAPK, improved several in vitro PLT parameters and prolonged infused PLT circulation in the in vivo mouse model after 14-days of storage at 4-6°C. Minocycline, a tetracyclic antibiotic, reduced platelet apoptosis during storage and kept mitochondrial membrane potential (MMP) stable after blue light exposure. This study assessed the impact of VX-702 and/or minocycline on PLTs stored at 4-6°C (CT) for 21 days.

Study

Design/Methods: Single apheresis PLT unit (n=6) in 100% plasma was aliquoted into four CLX storage bags (60-mL each) after collection. All bags were stored at room temperature with agitation before placing them at CT on Day 1 and stored for 21 days. One bag was designated as Control (CT). The second bag received 10 µM VX-702 on day 0 (CT-VX). The third bag had addition of 30 µM of minocycline (CT-Mino) at Day 0. The fourth bag had combination of both additions at the same time. Parameters measured were: PLT concentration, mean PLT volume, pH, glucose, lactate, pO2, pCO2, p-selectin (CD62P), tetraspanin 30 (CD63), GP IV (CD36), GPVI, integrin β1 (CD29), integrin α2b (CD41a), GPIX (CD42a), GP1bα (CD42b), phosphatidylserine exposure (annexin V binding), MMP (JC-1), reactive oxygen species (ROS) by CM-H2DCFDA and dihydroethidium (DHE). PLT in vitro parameters were evaluated on days 1, 7, 14, and 21 and analyzed by ANOVA for repeated measures with Bonferroni corrections for multiple comparisons.

Results/Findings: On day 21 (Table 1), PLT loss, PLT activation, integrins activation, GPIV, GPIX, annexin V binding, and ROS formation were statistically less in CT-VX and CT-VX-Mino aliquots compared to those of CT and CT-Mino. The levels of pH, GP1bα and MMP were statistically greater in CT-VX and CT-VX-Mino aliquots compared to those of CT and CT-Mino. There was no statistical difference between PLT parameters of CT-VX and CT-VX-Mino. GPVI was not impacted by addition of VX-702 or minocycline or their combination.


Conclusions:

Inhibition of p38 MAPK with VX-702 during 21-day storage in cold improved PLT retention and apoptosis while decreasing PLT and integrins activation, expression of GPIV, GPIX. VX-702 increases expression of GP1bα and improved mitochondrial function. Addition of minocycline did not improve PLT parameters or PLT mitochondrial function. VX-702 reduced cold storage-induced PLT lesion during 21-day storage and could improve logistics of providing PLTs to remote regions. This abstract reflects the views of the authors and should not be construed to represent FDA's views or policies.