Investigation of Lyophilized Platelet Interactions with Human Platelets In Vitro

B. Schnoor, A.-L. Papa
George Washington University,
United States

Keywords: lyophilized platelets, platelet aggregation, platelet adhesion, thrombosis

Summary:

Lyophilized Platelets have attracted attention as a replacement for current platelet transfusion due to their ease of storage and long-term stability [Bynum et al., 2019, Transfusion]. The development of lyophilized platelet systems could greatly expand the availability of transfusable platelets since they can be stored under less strict conditions for longer periods and with a lower risk of bacterial contamination [Fan et al., 2009, Sci. Bull.]. Furthermore, studies demonstrating the biocompatibility of lyophilized platelet formulations have indicated the possibility of using lyophilized platelets as a drug delivery system [Cellphire, 2017, NCT02223117; Barroso et al., 2018, Transfusion]. In order to explore these possibilities, however, the interactions between lyophilized platelets and untreated platelets found in the blood must be determined. Thus, the objective of this project is to characterize the interactions of platelets and lyophilized platelets through flow cytometry (receptor availability assay), light transmission aggregometry, and an LDH (lactate dehydrogenase)-based adhesion assay under normal and thrombocytopenic (low platelet count) conditions. The flow cytometry data demonstrates that the platelets maintain critical receptors needed for adhesion and aggregation function. The aggregometry data however indicates that the lyophilized platelets have an inhibitory effect on platelet aggregation. Conversely, the lyophilized platelets promote platelet adhesion in vitro. These trends are also found to hold true across normal and thrombocytopenic conditions. The data indicates that the intact adhesion receptors on the lyophilized platelets are able to aid with platelet adhesion, however, the largely inactivated aggregation receptors on the lyophilized platelet interfere with normal platelet aggregation. These trends indicate potential complications and further explain the interactions involved with a transfusion of lyophilized platelets. Furthermore, this information provides insights into how lyophilized platelets could be used as a drug delivery system. The inhibition of platelet aggregation by lyophilized platelets could provide an interesting functionality for an anticoagulant delivery system. Likewise, the increased adhesion with a lyophilized platelet transfusion could offer an opportunity for targeted delivery. Further research is needed to investigate these possibilities and develop appropriate delivery systems based on the characterization of the interactions of lyophilized platelets and untreated platelets presented here.