Platelets loaded with liposome‐encapsulated thrombin have increased coagulability

Abstract

Background Platelets are integral to clot formation and are often transfused to stop or prevent bleeding. However, transfusions of platelets are not always effective, particularly in the most severe cases of hemorrhage. Nanoparticle systems have been developed to mimic platelets but inherently lack important aspects of platelet function, which limits their potential effectiveness. Objectives Increasing the natural coagulability of transfusable platelets could increase their efficacy during treatment of severe hemorrhage. Thrombin is a potent platelet agonist that currently cannot be used intravenously because of the risk of thrombosis. We hypothesized that delivery of thrombin to ex vivo platelets via liposomal encapsulation would enable transfusable platelets to become more coagulable in response to platelet agonists. Methods Thrombin was encapsulated into nanoliposomes and delivered to platelets ex vivo. Platelet coagulability was measured by monitoring platelet activation, clot contraction, clot time and clot stability in several in vitro assays. These parameters were also measured under conditions where coagulation is compromised, including during acidosis, antiplatelet drugs, hemophilia A and trauma-induced coagulopathy. Results Liposomal thrombin was endocytosed and used by platelets ex vivo but was not secreted upon activation. These modified platelets became more sensitive and responsive to agonists and improved clotting time even under conditions that normally cause platelet dysfunction or have impaired coagulation. Conclusions Several aspects of platelet function were enhanced by ex vivo delivery of liposomal thrombin.

Delivery of mRNA to platelets using lipid nanoparticles

“…Plasma proteins can bind to LNPs, which affects their ability to be internalized by cells 22 . While the effect of incubating platelets in buffer before reconstituting in plasma was not fully characterized in this paper, we have previously shown that platelets prepared with protein-loaded LNPs can still clot blood in vitro after short periods of storage in buffer 27 . Here, the icLNPs did not activate the platelets or affect their ability to aggregate or spread.…”

Platelets and Fibrinogen: Emerging Complexity in Trauma-Induced Coagulopathy

“…Incorporating thrombin-containing liposomes into platelets prior to transfusion can increase their thrombogenicity likely by platelet incorporation of thrombin and subsequent release upon activation at an injury site. 57 Platelet-derived microparticles (PMPs) have shown possible therapeutic benefit in promoting hemostasis. These microparticles of platelet cell membrane are procoagulant, 58,59 and their levels in circulation increase after injury.…”

Hemostatic agents for prehospital hemorrhage control: a narrative review

“…However, another study showed that the platelet-derived hemostatic agent could neither reduce ear bleeding time nor improve clot strength in a rabbit thrombocytopenic model [117]. The limited efficacy, immunogenicity and risk of pathogen infection prompt the development of new intravenous hemostats, including synthetic platelets and polymers [46,49], and platelets loaded with liposomeencapsulated thrombin [118].…”