Platelet-inspired synthetic nanoparticles improve hemostasis and hemodynamics in a rabbit model of abdominal hemorrhage
Amudan J. Srinivasan, Zachary A. Secunda, Roberto I. Mota-Alvidrez, Norman F. Luc, Dante Disharoon, Baylee Traylor, Christa L. Pawlowski, Joshua B. Brown, Michael A. Bruckman, Anirban Sen Gupta, Matthew D. Neal- Critical Care and Intensive Care Medicine
- Surgery
Abstract
Background
Early platelet transfusion is associated with reduced mortality in traumatic hemorrhage. However, platelet usage is severely limited due to challenges of donor availability, platelet portability and storage. Here, we report on a bio-inspired synthetic platelet (SP) nanoconstruct that utilizes liposome surface-decoration with peptides that mimic injury site-specific platelet adhesion to vWF and collagen, and fibrinogen-mediated platelet aggregation. SP has previously shown promising hemostatic outcomes in vitro and in vivo. Here we evaluated hemostasis and hemodynamic effects of SP in a rabbit model of abdominal hemorrhage.
Methods
23 adult male New Zealand white rabbits (2.5-3.5 kg) were treated with either buffer, control particles (CP), or SP. Under general anesthesia with invasive monitoring, rabbits underwent laparotomy with combined splenic and hepatic injury. Hemodynamics were monitored for 30 minutes and blood loss was quantified. Blood counts, aggregometry, catecholamine and platelet factor 4 (PF4) assays were performed at multiple timepoints. Analysis used ANOVA and post-hoc Tukey testing with α = 0.05.
Results
Rabbits in the SP (n = 7) group had significantly lower weight-normalized blood loss compared to both buffer (n = 8) and CP (n = 8) animals (21.1 vs 33.2 vs 40.4 g/kg, p < 0.001). SP-treated animals had higher systolic blood pressure area-under-curve (AUC) compared to buffer- and CP-treated animals (1567 vs 1281 vs 1109 mmHg*min, p = 0.006), though post-hoc differences were only significant for the SP:CP comparison (p = 0.005). Platelet counts, catecholamine levels, PF4 and aggregometry were similar between groups.
Conclusions
SP treatment significantly reduced blood loss and improved hemodynamics in a rabbit abdominal hemorrhage model. SP has potential as an intravenous hemostatic platelet surrogate with donor-independent availability and scalable manufacture.