Hemostatic nanoparticles reduce mortality following blast trauma
Minimizing bleeding is essential to save lives following major injuries, but existing options to control internal bleeding have major limitations. The two currently available therapies include allogeneic platelets, which have a short shelf life and can cause immune reactions, and recombinant clotting factor 7 (NovoSeven), which is extremely expensive, can trigger thromboembolic events and has not been shown to reliably reduce mortality. These challenges have led several groups to design synthetic platelet substitutes consisting of polymeric nano- or microparticles or liposomes decorated with peptides that bind activated platelets, which accelerates clotting.
One of these groups, led by Erin Lavik at Case Western Reserve University, has recently shown that their synthetic platelets, which they term hemostatic nanoparticles, reduce mortality and lung injury in mice exposed to pressure waves mimicking a blast. This advance is especially impressive given that no animal model of blast trauma yet existed. Further, blast trauma causes multiple severe injuries and is likely one of the most challenging settings in which these nanoparticles might be used.
The Lavik lab’s hemostatic nanoparticles consist of poly(lactic-co-glycolic) acid (PLGA) and poly(L-lysine) cores coated with polyethylene glycol chains conjugated to GRGDS (glycine-arginine-glycine-aspartate-serine) peptides, which bind to the activated platelet receptors glycoprotein IIb-IIIa and integrin αvβ3. These particles have been shown over the past five years to halve bleeding time following femoral artery injury and to increase survival following blunt trauma injury. In the most recent study, hemostatic nanoparticles reduced mortality following a 20 psi pressure wave from 40% (4/10 mice) to 5% (1/11 mice). While this effect was larger than that of NovoSeven or nanoparticles to which a control peptide (that would not bind activated platelet receptors) was conjugated, these differences were not significant because of the necessarily small sample size.
As these nanoparticles remain effective even after two weeks of storage at room temperature, they represent a promising alternative to biologically-derived blood products. Nonetheless, studies in larger animals are required before clinical trials may begin.
Lashof-Sullivan MM, Shoffstall E, Atkins KT, Keane N, Bir C, VandeVord P, Lavik EB. Intravenously administered nanoparticles increase survival following blast trauma. Proc Nat Acad Sci USA 2014; published online June 30.